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1. Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer’s disease

Author: Lihua Wang, Niko-Petteri Nykänen, Daniel Western, Priyanka Gorijala, Jigyasha Timsina, Fuhai Li, Zhaohua Wang, Muhammad Ali, Chengran Yang, Menghan Liu, William Brock, Marta Marquié, Mercè Boada, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Agustín Ruiz, Raquel Puerta, Adelina Orellana, Jarod Rutledge, Hamilton Oh, Michael D Greicius, Yann Le Guen, Richard J. Perrin, Tony Wyss-Coray, Angela Jefferson, Timothy J. Hohman, Neill Graff-Radford, Hiroshi Mori, Alison Goate, Johannes Levin, Yun Ju Sung, and Carlos Cruchaga
Subjects: Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6
Abstract: Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a critical role in microglial activation, survival, and apoptosis, as well as in Alzheimer’s disease (AD) pathogenesis. We previously reported the MS4A locus as a key modulator for soluble TREM2 (sTREM2) in cerebrospinal fluid (CSF). To identify additional novel genetic modifiers of sTREM2, we performed the largest genome-wide association study (GWAS) and identified four loci for CSF sTREM2 in 3,350 individuals of European ancestry. Through multi-ethnic fine mapping, we identified two independent missense variants (p.M178V in MS4A4A and p.A112T in MS4A6A) that drive the association in MS4A locus and showed an epistatic effect for sTREM2 levels and AD risk. The novel TREM2 locus on chr 6 contains two rare missense variants (rs75932628 p.R47H, P=7.16×10-19; rs142232675 p.D87N, P=2.71×10-10) associated with sTREM2 and AD risk. The third novel locus in the TGFBR2 and RBMS3 gene region (rs73823326, P=3.86×10-9) included a regulatory variant with a microglia-specific chromatin loop for the promoter of TGFBR2. Using cell-based assays we demonstrate that overexpression and knock-down of TGFBR2, but not RBMS3, leads to significant changes of sTREM2. The last novel locus is located on the APOE region (rs11666329, P=2.52×10-8), but we demonstrated that this signal was independent of APOE genotype. This signal colocalized with cis-eQTL of NECTIN2 in the brain cortex and cis-pQTL of NECTIN2 in CSF. Overexpression of NECTIN2 led to an increase of sTREM2 supporting the genetic findings. To our knowledge, this is the largest study to date aimed at identifying genetic modifiers of CSF sTREM2. This study provided novel insights into the MS4A and TREM2 loci, two well-known AD risk genes, and identified TGFBR2 and NECTIN2 as additional modulators involved in TREM2 biology.
Published: 2024
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2. Proteome wide association studies of LRRK2 variants identify novel causal and druggable proteins for Parkinson’s disease

Author: Bridget Phillips, Daniel Western, Lihua Wang, Jigyasha Timsina, Yichen Sun, Priyanka Gorijala, Chengran Yang, Anh Do, Niko-Petteri Nykänen, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, John C. Morris, Suzanne E. Schindler, Anne M. Fagan, Raquel Puerta, Pablo García-González, Itziar de Rojas, Marta Marquié, Mercè Boada, Agustin Ruiz, Joel S. Perlmutter, Dominantly Inherited Alzheimer Network (DIAN) Consortia, Laura Ibanez, Richard J. Perrin, Yun Ju Sung, and Carlos Cruchaga
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Common and rare variants in the LRRK2 locus are associated with Parkinson’s disease (PD) risk, but the downstream effects of these variants on protein levels remain unknown. We performed comprehensive proteogenomic analyses using the largest aptamer-based CSF proteomics study to date (7006 aptamers (6138 unique proteins) in 3107 individuals). The dataset comprised six different and independent cohorts (five using the SomaScan7K (ADNI, DIAN, MAP, Barcelona-1 (Pau), and Fundació ACE (Ruiz)) and the PPMI cohort using the SomaScan5K panel). We identified eleven independent SNPs in the LRRK2 locus associated with the levels of 25 proteins as well as PD risk. Of these, only eleven proteins have been previously associated with PD risk (e.g., GRN or GPNMB). Proteome-wide association study (PWAS) analyses suggested that the levels of ten of those proteins were genetically correlated with PD risk, and seven were validated in the PPMI cohort. Mendelian randomization analyses identified GPNMB, LCT, and CD68 causal for PD and nominate one more (ITGB2). These 25 proteins were enriched for microglia-specific proteins and trafficking pathways (both lysosome and intracellular). This study not only demonstrates that protein phenome-wide association studies (PheWAS) and trans-protein quantitative trail loci (pQTL) analyses are powerful for identifying novel protein interactions in an unbiased manner, but also that LRRK2 is linked with the regulation of PD-associated proteins that are enriched in microglial cells and specific lysosomal pathways.
Published: 2023
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3. Brainstem neuromelanin and iron MRI reveals a precise signature for idiopathic and LRRK2 Parkinson’s disease

Author: Martín Martínez, Mikel Ariz, Ignacio Alvarez, Gabriel Castellanos, Miquel Aguilar, Jorge Hernández-Vara, Núria Caballol, Alicia Garrido, Àngels Bayés, Dolores Vilas, Maria Jose Marti, the Catalonian Neuroimaging Parkinson’s disease Consortium, Pau Pastor, Carlos Ortiz de Solórzano, and Maria A. Pastor
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson’s disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson’s disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.
Published: 2023
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4. Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson’s disease

Author: Saul Martínez-Horta, Helena Bejr-Kasem, Andrea Horta-Barba, Berta Pascual-Sedano, Diego Santos-García, Teresa de Deus-Fonticoba, Silvia Jesús, Miquel Aguilar, Lluis Planellas, Juan García-Caldentey, Nuria Caballol, Bárbara Vives-Pastor, Jorge Hernández-Vara, Iria Cabo-Lopez, Lydia López-Manzanares, Isabel González-Aramburu, Maria Asunción Ávila-Rivera, Maria Jose Catalán, Luis Manuel López-Díaz, Victor Puente, Jose Manuel García-Moreno, Carmen Borrué, Berta Solano-Vila, Maria Álvarez-Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo-Padilla, Juan Carlos Martínez-Castrillo, Pilar Sánchez-Alonso, Maria Gema Alonso-Losada, Nuria López-Ariztegui, Itziar Gastón, Marta Blázquez-Estrada, Manual Seijo-Martínez, Javier Rúiz-Martínez, Caridad Valero-Merino, Monica Kurtis, Oriol de Fábregues-Boixar, Jessica González-Ardura, Cristina Prieto-Jurczynska, Pablo Martinez-Martin, Pablo Mir, Jaime Kulisevsky, and COPPADIS Study Group
Subjects: Parkinson’s disease, PD-MCI, Cognition, Lifestyle, Coppadis, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson’s disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p
Published: 2021
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5. Predictors of clinically significant quality of life impairment in Parkinson’s disease

Author: Santos García D., Teresa de Deus Fonticoba, Carlos Cores, Guillermo Muñoz, Jose M. Paz González, Cristina Martínez Miró, Ester Suárez, Silvia Jesús, Miquel Aguilar, Pau Pastor, Lluis Planellas, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Luis López Manzanares, Isabel González Aramburu, María A. Ávila Rivera, Maria J. Catalán, Víctor Nogueira, Víctor Puente, María Ruíz de Arcos, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Pedro Clavero, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin, Pablo Mir, and COPPADIS Study Group
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson’s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p
Published: 2021
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6. Validity and sensitivity of instrumented postural and gait assessment using low-cost devices in Parkinson’s disease

Author: Ignacio Álvarez, Jorge Latorre, Miquel Aguilar, Pau Pastor, and Roberto Llorens
Subjects: Parkinson’s disease, Gait, Posture, Kinect, Wii balance board, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Background Accurate assessment of balance and gait is necessary to monitor the clinical progress of Parkinson’s disease (PD). Conventional clinical scales can be biased and have limited accuracy. Novel interactive devices are potentially useful to detect subtle posture or gait-related impairments. Methods Posturographic and single and dual-task gait assessments were performed to 54 individuals with PD and 43 healthy controls with the Wii Balance Board and the Kinect v2 and the, respectively. Individuals with PD were also assessed with the Tinetti Performance Oriented Mobility Assessment, the Functional Gait Assessment and the 10-m Walking Test. The influence of demographic and clinical variables on the performance in the instrumented posturographic and gait tests, the sensitivity of these tests to the clinical condition and phenotypes, and their convergent validity with clinical scales were investigated. Results Individuals with PD in H&Y I and I.5 stages showed similar performance to controls. The greatest differences in posture and gait were found between subjects in H&Y II.5 and H&Y I–I.5 stage, as well as controls. Dual-tasking enhanced the differences among all groups in gait parameters. Akinetic/rigid phenotype showed worse postural control and gait than other phenotypes. High significant correlations were found between the limits of stability and most of gait parameters with the clinical scales. Conclusions Low-cost devices showed potential to objectively quantify posture and gait in established PD (H&Y ≥ II). Dual-tasking gait evaluation was more sensitive to detect differences among PD stages and compared to controls than free gait. Gait and posture were more impaired in akinetic/rigid PD.
Published: 2020
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7. Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease

Author: Laura Ibanez, Jorge A. Bahena, Chengran Yang, Umber Dube, Fabiana H. G. Farias, John P. Budde, Kristy Bergmann, Carol Brenner-Webster, John C. Morris, Richard J. Perrin, Nigel J. Cairns, John O’Donnell, Ignacio Álvarez, Monica Diez-Fairen, Miquel Aguilar, Rebecca Miller, Albert A. Davis, Pau Pastor, Paul Kotzbauer, Meghan C. Campbell, Joel S. Perlmutter, Herve Rhinn, Oscar Harari, Carlos Cruchaga, and Bruno A. Benitez
Subjects: Parkinson disease, GWAS, Alpha-synuclein, Amyloid beta, APOE, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson’s disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta1–42, total tau, and phosphorylated tau181 as quantitative traits in genetic studies have provided novel insights into Alzheimer’s disease pathophysiology. A systematic study of the genomic architecture of CSF biomarkers in Parkinson’s disease has not yet been conducted. Here, genome-wide association studies of CSF biomarker levels in a cohort of individuals with Parkinson’s disease and controls (N = 1960) were performed. PD cases exhibited significantly lower CSF biomarker levels compared to controls. A SNP, proxy for APOE ε4, was associated with CSF amyloid beta1–42 levels (effect = − 0.5, p = 9.2 × 10−19). No genome-wide loci associated with CSF alpha-synuclein, total tau, or phosphorylated tau181 levels were identified in PD cohorts. Polygenic risk score constructed using the latest Parkinson’s disease risk meta-analysis were associated with Parkinson’s disease status (p = 0.035) and the genomic architecture of CSF amyloid beta1–42 (R2 = 2.29%; p = 2.5 × 10−11). Individuals with higher polygenic risk scores for PD risk presented with lower CSF amyloid beta1–42 levels (p = 7.3 × 10−04). Two-sample Mendelian Randomization revealed that CSF amyloid beta1–42 plays a role in Parkinson’s disease (p = 1.4 × 10−05) and age at onset (p = 7.6 × 10−06), an effect mainly mediated by variants in the APOE locus. In a subset of PD samples, the APOE ε4 allele was associated with significantly lower levels of CSF amyloid beta1–42 (p = 3.8 × 10−06), higher mean cortical binding potentials (p = 5.8 × 10−08), and higher Braak amyloid beta score (p = 4.4 × 10−04). Together these results from high-throughput and hypothesis-free approaches converge on a genetic link between Parkinson’s disease, CSF amyloid beta1–42, and APOE.
Published: 2020
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8. Heritability and genetic variance of dementia with Lewy bodies

Author: Rita Guerreiro, Valentina Escott-Price, Dena G. Hernandez, Celia Kun-Rodrigues, Owen A. Ross, Tatiana Orme, Joao Luis Neto, Susana Carmona, Nadia Dehghani, John D. Eicher, Claire Shepherd, Laura Parkkinen, Lee Darwent, Michael G. Heckman, Sonja W. Scholz, Juan C. Troncoso, Olga Pletnikova, Ted Dawson, Liana Rosenthal, Olaf Ansorge, Jordi Clarimon, Alberto Lleo, Estrella Morenas-Rodriguez, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Ekaterina Rogaeva, Peter St. George-Hyslop, Elisabet Londos, Henrik Zetterberg, Imelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, Geidy E. Serrano, Thomas G. Beach, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Neill Graff-Radford, Nigel J. Cairns, John C. Morris, Stuart Pickering-Brown, David Mann, Glenda M. Halliday, John Hardy, John Q. Trojanowski, Dennis W. Dickson, Andrew Singleton, David J. Stone, and Jose Bras
Subjects: Genetic variance, Dementia, Lewy bodies, Genetic correlation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.
Published: 2019
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9. A Review on Tramiprosate (Homotaurine) in Alzheimer's Disease and Other Neurocognitive Disorders

Author: Sagrario Manzano, Luis Agüera, Miquel Aguilar, and Javier Olazarán
Subjects: homotaurine, tramiprosate, amyloid, Alzheimer's disease, neurocognitive disorders, neurodegenerative diseases, Neurology. Diseases of the nervous system, RC346-429
Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative condition, especially among elderly people. The presence of cortical β-amyloid deposition, together with tau phosphorylation and intracellular accumulation of neurofibrillary tangles (NFT) is the main neuropathologic criteria for AD diagnosis. Additionally, a role of inflammatory, mitochondrial, and metabolic factors has been suggested. Tramiprosate binds to soluble amyloid, thus inhibiting its aggregation in the brain. It reduced oligomeric and fibrillar (plaque) amyloid, diminished hippocampal atrophy, improved cholinergic transmission, and stabilized cognition in preclinical and clinical studies. In this narrative review, current information on the efficacy and safety of tramiprosate, both in AD and in other neurocognitive disorders, is presented. Possible directions for future studies with tramiprosate are also discussed.
Published: 2020
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10. Motor Fluctuations Development Is Associated with Non-Motor Symptoms Burden Progression in Parkinson’s Disease Patients: A 2-Year Follow-Up Study

Author: Diego Santos-García, Teresa de Deus Fonticoba, Carlos Cores Bartolomé, Maria J. Feal Painceiras, Ester Suárez Castro, Héctor Canfield, Cristina Martínez Miró, Silvia Jesús, Miquel Aguilar, Pau Pastor, Lluís Planellas, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Ines Legarda, Jorge Hernández-Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, Maria A. Ávila Rivera, Víctor Gómez Mayordomo, Víctor Nogueira, Víctor Puente, Julio Dotor García-Soto, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Ruben Alonso Redondo, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin, Pablo Mir, and COPPADIS Study Group
Subjects: burden, follow-up, non-motor symptoms, motor fluctuations, Parkinson’s disease, Medicine (General), R5-920
Abstract: Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.
Published: 2022
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11. Diplopia Is Frequent and Associated with Motor and Non-Motor Severity in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up

Author: Diego Santos García, Lucía Naya Ríos, Teresa de Deus Fonticoba, Carlos Cores Bartolomé, Lucía García Roca, Maria Feal Painceiras, Cristina Martínez Miró, Hector Canfield, Silvia Jesús, Miquel Aguilar, Pau Pastor, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, María A. Ávila Rivera, Víctor Gómez Mayordomo, Víctor Nogueira, Víctor Puente, Julio Dotor, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Ruben Alonso Redondo, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin, and Pablo Mir
Subjects: changes, motor, Parkinson’s disease, phenotype, PIGD, Tremor, Medicine (General), R5-920
Abstract: Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.
Published: 2021
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12. Neuropsychological Outcome One Year after Carotid Revascularization: A before-and-after Study

Author: Laura Casas-Hernanz, Maite Garolera, Dolors Badenes, Salvador Quintana, Susana Mill?n, Noemi Calzado, Jorge de Francisco, Josep Royo, and Miquel Aguilar
Subjects: Endarterectomy, Carotid stenosis, Angioplasty, Cognition, Neuropsychological tests, Diseases of the blood and blood-forming organs, RC633-647.5, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Purpose: The aim of our study was to determine the clinical profile of patients considered cognitive ‘responders’ to surgery in order to establish clinical variables associated with a favorable cognitive performance. Materials and Methods: A total of 70 patients were included in the study. A well-validated, comprehensive standardized neurocognitive battery of tests of about 2 hours was administered. Patients were examined twice, 1-week before surgery and 1-year postoperatively. The criterion to be included in the ‘responder’ group was the following: to obtain a positive difference between post-revascularization and pre-revascularization neuropsychological assessment ≥1 standard deviation in ≥2 tests. Results: Twenty-seven patients (38.6%) were cognitive responders to treatment. In bivariate analysis between responders and non-responders, presence of atrophy (P=0.003), small vessels (P=0.577), symptoms (P=0.046), and age (P=0.030) were the factors statistically significant. When comparing cognitive performance before and after carotid revascularization, significant differences were observed in semantic fluency with a lower performance after 12 months (P=0.004, d=0.29), and in the Language index (Repeatable Battery for the Assessment of Neuropsychological Status) (P=0.005, d=0.34). Conclusion: Patients without neurological symptoms, of a younger age and without atrophy and white matter small vessel lesions are better cognitive responders 1-year after carotid revascularization.
Published: 2017
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13. Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

Author: Diego Santos García, Teresa de Deus Fonticoba, Carlos Cores Bartolomé, Lucía Naya Ríos, Lucía García Roca, Cristina Martínez Miró, Hector Canfield, Silvia Jesús, Miquel Aguilar, Pau Pastor, Marina Cosgaya, Juan García Caldentey, Nuria Caballol, Inés Legarda, Jorge Hernández Vara, Iria Cabo, Lydia López Manzanares, Isabel González Aramburu, María A. Ávila Rivera, Víctor Gómez Mayordomo, Víctor Nogueira, Víctor Puente, Julio Dotor, Carmen Borrué, Berta Solano Vila, María Álvarez Sauco, Lydia Vela, Sonia Escalante, Esther Cubo, Francisco Carrillo Padilla, Juan C. Martínez Castrillo, Pilar Sánchez Alonso, Maria G. Alonso Losada, Nuria López Ariztegui, Itziar Gastón, Jaime Kulisevsky, Marta Blázquez Estrada, Manuel Seijo, Javier Rúiz Martínez, Caridad Valero, Mónica Kurtis, Oriol de Fábregues, Jessica González Ardura, Ruben Alonso Redondo, Carlos Ordás, Luis M. López Díaz, Darrian McAfee, Pablo Martinez-Martin, Pablo Mir, and COPPADIS Study Group
Subjects: activities of daily living, dependency, disability, gait, Parkinson’s disease, Medicine (General), R5-920
Abstract: Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.
Published: 2021
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14. El 'Llibre de l'orde de cavalleria' en el context sociocultural medieval

Author: Miquel Aguilar i Montero
Subjects: Chivalry, Ramon Llull, Middle Ages, society, culture, Language and Literature, French literature - Italian literature - Spanish literature - Portuguese literature, PQ1-3999
Abstract: Ramon Llull wrote his Llibre de l’orde de cavalleria under the influence of a time and a mentality strongly characterized for the socio-cultural medieval context. The article explains how to understand this work’s implementation due to the quaternary phase of Ramon Llull’s Art, with its virtues and sins; the 13th century geopolitical situation, especially everything connected with chivalry, and the chivalry’s treaties done or known at that period’s Kingdom of Aragon.
Published: 2010

15. La reescritura de la leyenda de Tristán e Iseo en 'Cligès'

Author: Miquel Aguilar i Montero
Subjects: Chrétien de Troyes, Cligès y Fenice, Tristán e Iseo, siglo xii, amor cortés, nuevo sen, Language and Literature, French literature - Italian literature - Spanish literature - Portuguese literature, PQ1-3999
Abstract: La obra "Cligès", de Chrétien de Troyes, ha sido tradicionalmente considerada por la crítica como una reescritura moralista de la leyenda de Tristán e Iseo. El nuevo sen aplicado por este poeta francés no solo se aplica en el sentido de una relectura del amor cortés más ortodoxa, sino también en el de un mayor realismo literario, más racional y moderno en términos estilísticos. Amor, pasión y adulterio, bajo la pluma de Chrétien, se convierten en nuevos conceptos aptos para establecer una distancia e incluso una confrontación contra el libertinaje poético de sus coetáneos normandos.
Published: 2014
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16. Nonmotor symptoms in LRRK2 G2019S associated Parkinson's disease.

Author: Carles Gaig, Dolores Vilas, Jon Infante, María Sierra, Inés García-Gorostiaga, Mariateresa Buongiorno, Mario Ezquerra, Maria José Martí, Francesc Valldeoriola, Miquel Aguilar, Matilde Calopa, Jorge Hernandez-Vara, and Eduardo Tolosa
Subjects: Medicine, Science
Abstract: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients.The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated.University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p
Published: 2014
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17. Motius folklòrics al Tristany i Iseut

Author: Miquel Aguilar i Montero
Subjects: Tristany i Iseut, segle xii, folklore, motius literaris, Language and Literature, French literature - Italian literature - Spanish literature - Portuguese literature, PQ1-3999
Abstract: L’article aplega i analitza els principals motius folklòrics de Tristany i Iseut i els classifica segons l’índex del folklorista Stith Thompson.
Published: 2014
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18. Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease

Author: Sampedro, Frederic, Martínez-Horta, Saul, Horta-Barba, Andrea, Grothe, Michel J., Labrador-Espinosa, Miguel A., Jesús, Silvia, Adarmes-Gómez, Astrid, Carrillo, Fátima, Puig-Davi, Arnau, Lora, Florinda Roldán, Barberá, Miquel Aguilar, Pastor, Pau, Arroyo, Sonia Escalante, Vila, Berta Solano, Foraster, Anna Cots, Martínez, Javier Ruiz, Padilla, Francisco Carrillo, Morlans, Mercedes Pueyo, Aramburu, Isabel González, Ceberio, Jon Infante, Vara, Jorge Hernández, de Fábregues-Boixar, Oriol, de Deus Fonticoba, Teresa, Ávila, Asunción, Martínez-Castrillo, Juan Carlos, Bejr-Kasem, Helena, Campolongo, Antonia, Pascual-Sedano, Berta, Martínez-Martín, Pablo, Santos-García, Diego, Mir, Pablo, and Kulisevsky, Jaime
Published: 2022
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19. In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study

Author: Grothe, Michel J., Labrador-Espinosa, Miguel A., Jesús, Silvia, Macías-García, Daniel, Adarmes-Gómez, Astrid, Carrillo, Fátima, Camacho, Elena Iglesias, Franco-Rosado, Pablo, Lora, Florinda Roldán, Martín-Rodríguez, Juan Francisco, Barberá, Miquel Aguilar, Pastor, Pau, Arroyo, Sonia Escalante, Vila, Berta Solano, Foraster, Anna Cots, Martínez, Javier Ruiz, Padilla, Francisco Carrillo, Morlans, Mercedes Pueyo, Aramburu, Isabel González, Ceberio, Jon Infante, Vara, Jorge Hernández, de Fábregues-Boixar, Oriol, de Deus Fonticoba, Teresa, Pascual-Sedano, Berta, Kulisevsky, Jaime, Martínez-Martín, Pablo, Santos-García, Diego, and Mir, Pablo
Published: 2021
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20. Fortasyn Connect Improves Neuropsychiatric Symptoms in Patients with Mild Cognitive Impairment and Dementia: Results from a Retrospective Real-World Study

Author: Miquel Aguilar-Barberà, Paquita Soler-Girabau, Ana Isabel Tabuenca-Martín, and Laura Prieto-del Val
Subjects: Psychiatry and Mental health, Clinical Psychology, General Neuroscience, General Medicine, Geriatrics and Gerontology
Abstract: Background: Behavioral and psychological symptoms of dementia (BPSD) manifest in the early stages of the disease and impair patients’ and caregivers’ quality of life. Objective: To assess the effectiveness of the nutritional supplement Fortasyn Connect on BPSD for 12 months in people with mild cognitive impairment (MCI) and dementia in clinical practice. Methods: Retrospective, national, single-center study of 236 patients (158 MCI and 78 dementia; 55.1% of AD etiology). BPSD were assessed with the Neuropsychiatric Inventory (NPI) at month 3, 6, and 12. Cognition (Mini-Mental State Examination, MMSE), depression (Geriatric Depression Scale, GDS), and everyday functioning (Blessed Dementia Scale, BLS-D; Rapid Disability Rating Scale 2, RDRS2) were also evaluated. Results: Total NPI score, caregiver impact, and symptoms of depression, anxiety, apathy, and irritability improved after 3, 6, and 12 months from Fortasyn Connect initiation (p 20 points (p
Published: 2023
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21. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Author: Coleman, A, Santos, R Dar, Decolongon, J, Sturrock, A, Bardinet, E, Ret, C Jauff, Justo, D, Lehericy, S, Marelli, C, Nigaud, K, Valabrègue, R, van den Bogaard, SJA, Dumas, E M, van der Grond, J, t'Hart, EP, Jurgens, C, Witjes-Ane, M-N, Arran, N, Callaghan, J, Stopford, C, Frost, C, Jones, R, Hobbs, N, Lahiri, N, Ordidge, R, Owen, G, Pepple, T, Read, J, Say, M, Wild, E, Patel, A, Fox, N C, Gibbard, C, Malone, I, Crawford, H, Whitehead, D, Keenan, S, Cash, D M, Berna, C, Bechtel, N, Bohlen, S, Man, A Hoff, Kraus, P, Axelson, E, Wang, C, Acharya, T, Lee, S, Monaco, W, Campbell, C, Queller, S, Whitlock, K, Campbell, M, Frajman, E, Milchman, C, O'Regan, A, Labuschagne, I, Stout, J, Landwehrmeyer, B, Craufurd, D, Scahill, R, Hicks, S, Kennard, C, Johnson, H, Tobin, A, Rosas, HD, Reilmann, R, Borowsky, B, Pourchot, C, Andrews, S C, Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna Rita, Biunno, Ida, Bonelli, Raphael, Burgunder, Jean-Marc, Dunnett, Stephen, Ferreira, Joaquim, Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Landwehrmeyer, G. Bernhard, Levey, Jamie, Ramos-Arroyo, Maria A., Nielsen, Jørgen, Koivisto, Susana Pro, Päivärinta, Markku, Roos, Raymund A.C., Sebastián, A Rojo, Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Garde, Monica Bascuñana, Betz, Sabrina, Bos, Reineke, Callaghan, Jenny, Come, Adrien, Guedes, Leonor Correia, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Gilling, Mette, Gustafsson, Lena, Handley, Olivia J, Hvalstedt, Carina, Held, Christine, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mütze, Lisanne, Oehmen, Martin, Orth, Michael, Padieu, Hélène, Paterski, Laurent, Peppa, Nadia, Di Renzo, Martina, Rialland, Amandine, Røren, Niini, Šašinková, Pavla, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, da Silva, Wildson Vieira, van Walsem, Marleen R, Whalstedt, Carina, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Bonelli, Raphael M., Lilek, Sabine, Hecht, Karen, Herranhof, Brigitte, Holl, Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Müller, Christoph, Poewe, Werner, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Boogaerts, Andrea, Calmeyn, Godelinde, Delvaux, Isabelle, Liessens, Dirk, Somers, Nele, Dupuit, Michel, Minet, Cécile, van Paemel, Dominique, Ribaï, Pascale, van Reijen, Dimphna, Klempír, Jirí, Majerová, Veronika, Roth, Jan, Stárková, Irena, Hjermind, Lena E., Jacobsen, Oda, Nielsen, Jørgen E., Larsen, Ida Unmack, Vinther-Jensen, Tua, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duché, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Barthélémy, Rekha, De Bruycker, Christelle, Carette, Maryline Cabaret Anne-Sophie, Defebvre, Eric Decorte Luc, Delliaux, Marie, Delval, Arnaud, Destee, Alain, Dujardin, Kathy, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Peter, Mireille, Plomhouse, Lucie, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Berrissoul, Hassan, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Godefroy, Olivier, Krystkowiak, Pierre, Mantaux, Béatrice, Roussel, Martine, Wannepain, Sandrine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Mundler, Laura, Anheim, Mathieu, Julié, Celine, Boukbiza, Ouhaid Lagha, Longato, Nadine, Rudolf, Gabrielle, Tranchant, Christine, Zimmermann, Marie-Agathe, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike Jakob, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kotz, Peter, Prehn, Christian, Saft, Carsten, Lange, Herwig, Maiwald, Robert, Löhle, Matthias, Maass, Antonia, Schmidt, Simone, Bosredon, Cecile, Storch, Alexander, Wolz, Annett, Wolz, Martin, Capetian, Philipp, Lambeck, Johann, Zucker, Birgit, Boelmans, Kai, Ganos, Christos, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Schmalfeld, Jenny, Stubbe, Lars, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Gorzolla, Heike, Schrader, Christoph, Tacik, Pawel, Ribbat, Michael, Longinus, Bernhard, Bürk, Katrin, Möller, Jens Carsten, Rissling, Ida, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Natalia, Dose, Matthias, Leythäuser, Gabriele, Marquard, Ralf, Raab, Tina, Wiedemann, Alexandra, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lang, Christina, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süßmuth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Cormio, Claudia, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Capellari, Sabina, Cortelli, Pietro, Galassi, Roberto, Rizzo, Giovanni, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Massaro, Francesca, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, di Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Albanese, Alberto, Di Bella, Daniela, Castaldo, Anna, Di Donato, Stefano, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Paridi, Dominga, Soliveri, Paola, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Amico, Enrico, Favellato, Mariagrazia, Griguoli, Annamaria, Mazzante, Irene, Petrollini, Martina, Squitieri, Ferdinando, D'Alessio, Barbara, Esposito, Chiara, Bentivoglio, Rita, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Piano, Carla, Romano, Silvia, Soleti, Francesco, Spadaro, Maria, van Hout, Monique S.E., Verhoeven, Marloes E., van Vugt, Jeroen P.P., de Weert, A. Marit, Bolwijn, J.J.W., Dekker, M., Kremer, B., Leenders, K.L., van Oostrom, J.C.H., van den Bogaard, Simon J.A., Dumas, Eve M., 't Hart, Ellen P., Kremer, Berry, Verstappen, C.C.P., Aaserud, Olaf, C, Jan Frich, Wehus, Ragnhild, Bjørgo, Kathrine, Fannemel, Madeleine, Gørvell, Per F., Lorentzen, Eirin, Retterstøl, Lars, Stokke, Bodil, Bjørnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wójcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlos, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badenes, Hernanz, Laura Casas, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Blas, Fenollar, María, García, Rocío García-Ramos, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuñana, Mónica, Caldentey, Juan Garcia, Ventura, Marta Fatás, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruíz, Pedro J García, Martínez-Descals, Asunción, Guerrero, Rosa, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivancos, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlos, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Arques, Penelope Navas, Rodríguez, María José Torres, Pastor, Barbara Vives, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolores, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peña, José Chacón, Redondo, Luis, Carrillo, Fátima, Teresa Cáceres, María, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andres, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnus, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jens, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Ho, Carrie, Hughes, Teresa, McGill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, McKenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klöppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thomas, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, Harrison, David, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Moss, Davina J Hensman, Pardiñas, Antonio F, Langbehn, Douglas, Lo, Kitty, Leavitt, Blair R, Roos, Raymund, Durr, Alexandra, Mead, Simon, Holmans, Peter, and Tabrizi, Sarah J
Published: 2017
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22. Intermediate and Expanded <scp> HTT </scp> Alleles and the Risk for α‐Synucleinopathies

Author: Sergio Pérez‐Oliveira, Ignacio Álvarez, Irene Rosas, Manuel Menendez‐González, Marta Blázquez‐Estrada, Miquel Aguilar, Daniela Corte, Mariateresa Buongiorno, Laura Molina‐Porcel, Iban Aldecoa, María J. Martí, Pascual Sánchez‐Juan, Jon Infante, Isabel González‐Aramburu, Pablo García‐González, Maitée Rosende‐Roca, Mercè Boada, Agustín Ruiz, María Teresa Periñán, Daniel Macías‐García, Laura Muñoz‐Delgado, Pilar Gómez‐Garre, Pablo Mir, Jordi Clarimón, Alberto Lleo, Daniel Alcolea, Beatriz De la Casa‐Fages, Israel Duarte, Victoria Álvarez, Pau Pastor, Instituto de Salud Carlos III, European Commission, Asociación Parkinson Asturias, Obra Social Cajastur, Ministerio de Educación, Cultura y Deporte (España), Junta de Andalucía, Fundació Víctor Grifols i Lucas, Fundación 'la Caixa', Ace Alzheimer Center Barcelona, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Menéndez-González, Manuel, Infante, Jon, Mir, Pablo, Casa-Fages, Beatriz de la, and Álvarez, Victoria
Subjects: Male, Huntingtin Protein, Synucleinopathies, Parkinson's disease, Dementia with Lewy bodies, Multisystem atrophy, α-Synucleinopathies, Parkinson Disease, Multiple System Atrophy, HTT gene, Huntington Disease, Neurology, Humans, Neurology (clinical), Trinucleotide Repeat Expansion, Alleles
Abstract: [Background] Previous studies suggest a link between CAG repeat number in the HTT gene and non-Huntington neurodegenerative diseases., [Objective] The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α-synucleinopathies or their behavior as modulators of the phenotype., [Methods] We genotyped the HTT gene CAG repeat number and APOE-Ɛ isoforms in a case-control series including patients with either clinical or neuropathological diagnosis of α-synucleinopathy., [Results] We identified three Parkinson's disease (PD) patients (0.30%) and two healthy controls (0.19%) carrying low-penetrance HTT repeat expansions whereas none of the dementia with Lewy bodies (DLB) or multisystem atrophy (MSA) patients carried pathogenic HTT expansions. In addition, a clear increase in the number of HTT CAG repeats was found among DLB and PD groups influenced by the male gender and also by the APOE4 allele among DLB patients. HTT intermediate alleles' (IAs) distribution frequency increased in the MSA group compared with controls (8.8% vs. 3.9%, respectively). These differences were indeed statistically significant in the MSA group with neuropathological confirmation. Two MSA HTT CAG IAs carriers with 32 HTT CAG repeats showed isolated polyQ inclusions in pons and basal nuclei, which are two critical structures in the neurodegeneration of MSA., [Conclusions] Our results point to a link between HTT CAG number, HTT IAs, and expanded HTT CAG repeats with other non-HD brain pathology and support the hypothesis that they can share common neurodegenerative pathways., This work is supported by the Fondo de Investigaciones Sanitarias' Spanish government ICIII FIS-FEDER grants (ID grants: PI21/0467 to V.A., and PI21/00886 to P.P.). Sergio Pérez-Oliveira is supported by Fundación Parkinson Asturias-Obra Social Cajastur. M.T.P. was supported by the Spanish Ministry of Education, Culture and Sports [FPU16/05061]. D.M.-G. was supported by the “Río Hortega” program [CM18/00142] from the Instituto de Salud Carlos III (ISCIII-FEDER). P.G.-G. was supported by the “Nicolás Monardes” program [C-0048-2017] from the Andalusian Regional Ministry of Health. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa,” Fundació ACE, and CIBERNED. P.G. is supported by CIBERNED employment plan CNV-304-PRF-866. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by National Grants (PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301). Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”).
Published: 2022
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23. Smoking is associated with age at disease onset in Parkinson's disease

Author: Irene Rosas, Germán Morís, Eliecer Coto, Marta Blázquez-Estrada, Esther Suárez, Ciara García-Fernández, Carmen Martínez, Israel Duarte Herrera, Sergio Pérez-Oliveira, Victoria Álvarez, Manuel Menéndez-González, Astrid D. Adarmes-Gómez, Miquel Aguilar, Ignacio Alvarez, Francisco Javier Barrero, Jesús Alberto Bergareche Yarza, Marta Bonilla-Toribio, Juan A. Botía, María Teresa Boungiorno, Dolores Buiza-Rueda, Ana Cámara, Fátima Carrillo, Debora Cerdan, Jordi Clarimón, Yaroslau Compta, Monica Diez-Fairen, Oriol Dols-Icardo, Oriol de Fabregues, Pilar Sanz Cartagena, Jacinto Duarte, Raquel Duran, Francisco Escamilla-Sevilla, Mario Ezquerra, Cici Feliz, Rubén Fernández-Santiago, Manel Fernández, Pedro García-Ruiz, Pilar Gómez-Garre, Maria Jose Gomez Heredia, Isabel Gonzalez-Aramburu, Ana Gorostidi, Janet Hoenicka, Jon Infante, Silvia Jesús, Adriano Jimenez-Escrig, Jaime Kulisevsky, Miguel A. Labrador-Espinosa, Jose Luis Lopez-Sendon, Adolfo López de Munain, Daniel Macias-Garcia, Irene Martínez-Torres, Juan Marín, Maria Jose Marti, Juan Carlos Martínez-Castrillo, Marina Mata Álvarez-Santullano, Adolfo Mínguez-Castellanos, Pablo Mir, Elisabet Mondragon Rezola, Esteban Muñoz, Javier Pagonabarraga, Pau Pastor, Francisco Perez Errazquin, Maria Teresa Periñán, Javier Ruiz-Martínez, Clara Ruz, Antonio Sanchez Rodriguez, María Sierra, Cesar Tabernero, Juan Pablo Tartari, Eduard Tolosa, Francesc Valldeoriola, Lydia Vela, Francisco Vives, Berta Pascual-Sedano, Jorge Hernández-Vara, Dolores Vilas Rolán, Sara Bandrés-Ciga, Fundación José Luis Castaño, Obra Social Cajastur, European Commission, and Asociación Parkinson Asturias
Subjects: Cohort Studies, Male, Heterozygote, Apolipoproteins E, Neurology, Smoking, Humans, Parkinson Disease, Neurology (clinical), Age of Onset, Geriatrics and Gerontology, APOE
Abstract: [Background] Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients., [Objective] The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk., [Methods] We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results., [Results] Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001)., [Conclusions] Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD., Irene Rosas was supported by a grant from Fundación Jose Luis Castaño-SEQC. Sergio Pérez-Oliveira is supported by Fundación Parkinson Asturias-Obra Social Cajastur. This study was supported by grant PI 15/00878 (Fondos Feder) to VA.
Published: 2022
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24. Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Author: Pablo García-González, Itziar de Rojas, Sonia Moreno-Grau, Laura Montrreal, Raquel Puerta, Emilio Alarcón-Martín, Inés Quintela, Adela Orellana, Victor Andrade, Pamela V. Martino Adami, Stefanie Heilmann-Heimbach, Pilar Gomez-Garre, María Teresa Periñán, Ignacio Alvarez, Monica Diez-Fairen, Raul Nuñez Llaves, Claudia Olivé Roig, Guillermo Garcia-Ribas, Manuel Menéndez-González, Carmen Martínez, Miquel Aguilar, Mariateresa Buongiorno, Emilio Franco-Macías, Maria Eugenia Saez, Amanda Cano, Maria J. Bullido, Luis Miguel Real, Eloy Rodríguez-Rodríguez, Jose Luís Royo, Victoria Álvarez, Pau Pastor, Gerard Piñol-Ripoll, Pablo Mir, Miguel Calero Lara, Miguel Medina Padilla, Pascual Sánchez-Juan, Angel Carracedo, Sergi Valero, Isabel Hernandez, Lluis Tàrraga, Alfredo Ramirez, Mercé Boada, Agustín Ruiz, and UAM. Departamento de Biología Molecular
Subjects: Male, Mild Cognitive Impairment, genetics [Alzheimer Disease], Alzheimer’s disease, mosaic loss of chromosome Y, disease progression, GWAS, Mendelian randomization, GR@ACE/DEGESCO, EADB, mild cognitive impairment, polygenic risk score, CSF biomarkers, Catalysis, Inorganic Chemistry, Risk Factors, Humans, genetics [Amyloid beta-Peptides], Alzheimer’s Disease, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Polygenic Risk Score, Mosaicism, Organic Chemistry, genetics [Cognitive Dysfunction], General Medicine, Biología y Biomedicina / Biología, Computer Science Applications, genetics [tau Proteins], Mosaic Loss of Chromosome Y, ddc:540, genetics [Chromosomes, Human, Y], Disease Progression, Female, Biomarkers, Genome-Wide Association Study
Abstract: Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, los autores pertenecientes a la UAM y el nombre del grupo de colaboración, si lo hubiere, Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis
Published: 2023
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25. GWAS for CSF TREM2 levels identify new variants implicated on TREM2 biology and Alzheimer disease

Author: Samira Mafimoghaddam, Lihua Wang, Priyanka Gorijala, Jigyasha Timsina, Niko Nykanen, Fengxian Wang, Marta Marquié, Mercè Boada, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Agustín Ruiz, Yun Ju Sung, and Carlos Cruchaga
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022
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26. Identification of a sex-specific genetic signature in dementia with Lewy bodies: a meta-analysis of genome-wide association studies

Author: Elizabeth Gibbons, Arvid Rongve, Itziar de Rojas, Alexey Shadrin, Kaitlyn Westra, Allison Baumgartner, Levi Rosendall, Zachary Madaj, Dena G. Hernandez, Owen A. Ross, Valentina Escott-Price, Claire Shepherd, Laura Parkkinen, Sonja W. Scholz, Juan C. Troncoso, Olga Pletnikova, Ted Dawson, Liana Rosenthal, Olaf Ansorge, Jordi Clarimon, Alberto Lleo, Estrella Morenas-Rodriguez, Lorraine Clark, Lawrence S Honig, Karen Marder, Afina Lemstra, Ekaterina Rogaeva, Peter St. George-Hyslop, Elisabet Londos, Henrik Zetterberg, Kevin Morgan, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, Geidy E Serrano, Thomas G Beach, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Marta Marquie, Pablo Garcia-Gonzalez, Claudia Olive, Raquel Puerta, Amanda Cano, Oscar Sotolongo-Grau, Sergi Valero, Vanesa Veronica Pytel, Maitee Rosende-Roca, Montserrat Alegret, Lluis Tarraga, Merce Boada, Angel Carracedo, Emilio Franco-Macias, Jordi Perez-Tur, Jose Luis Royo, Jose Maria Garcia-Alberca, Luis Miguel Real, Maria Eugenia Saez, Maria Jesus Bullido, Miguel Calero, Miguel Medina, Pablo Mir, Pascual Sanchez-Juan, Victoria Alvarez, Kayenat Parveen, Kumar Parijat Tripathi, Stefanie Heilmann-Heimbach, Alfredo Ramirez, Pentti J. Tienari, Olivier Bousiges, Frederic Blanc, Chiara Fenoglio, Alessandro Padovani, Barbara Borroni, Andrea Pilotto, Flavio Nobili, Ingvild Saltvedt, Tormod Fladby, Geir Selbaek, Ingunn Bosnes, Geir Brathen, Annette Hartmann, Afina W. Lemstra, Dan Rujescu, Brit Mollenhauer, Byron Creese, Marie-Christine Chartier-Harlin, Lavinia Athanasiu, Srdjan Djurovic, Leonidas Chouliaras, John T. OBrien, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F Boeve, Ronald C. Petersen, Tanis J Ferman, Neill Graff-Radford, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, John Hardy, Dennis W. Dickson, Andrew Singleton, David J. Stone, Ole A. Andreassen, Agustin Ruiz, Dag Aarsland, Rita Guerreiro, and Jose Bras
Abstract: BackgroundGenome-wide Association Studies (GWAS) have reshaped our understanding of the genetic bases of complex diseases in general and neurodegenerative diseases in particular. Despite being a common disorder, dementia with Lewy bodies (DLB), which, together with Parkinson’s disease dementia (PDD), comprise the umbrella term Lewy body dementias (LBD), is far from being well-characterized genetically. This is primarily due to a lack of familial cases and difficulty recruiting large, deeply characterized cohorts, given the high rate of misdiagnosis. By performing the largest GWAS in DLB, we aimed to identify novel risk loci to gain a better understanding of this disease’s pathobiology.MethodsHere, we conducted the largest meta-analysis of genome-wide association studies performed in LBD, using a total of 5,119 cases and 20,988 controls, from five independent datasets, aggregating all previously published DLB genome-wide association results to date, as well as two previously undescribed cohorts. Additionally, we performed a sex stratified GWAS using the discovery datasets. We updated the heritability estimates for DLB and, to fine map these estimates, we used local heritability analysis. We calculated genetic correlation estimates between DLB and a range of other diseases and traits to identify potential pleiotropy. We also performed gene-set analysis to identify genes with excess burden of rare variability and pathway analysis. Lastly, we used the UK Biobank data to perform a PheWas using individuals at the extremes of genetic risk for DLB.FindingsBetween November 2018 and September 2022 we analyzed 8.6 million single nucleotide polymorphisms in 3293 DLB cases, 1826 LBD cases and 20,988 controls, as well as phenotypes from the UK Biobank dataset. Despite more than doubling the sample size from the previous GWAS in DLB, we did not identify significant loci in addition to those previously reported atGBA, SNCA, STX1B, andAPOE. However, the sex-stratified analysis revealed that theGBAandSNCAsignals are mainly driven by males, suggesting a sex-specific genetic architecture of disease. Using only clinical and neuropathologically diagnosed cases, we highlight four loci surpassing the significance threshold. Using the largest cohort of DLB we update our heritability estimates to 13% and fine map these results highlighting regions of the genome with high heritability but no genome-wide significant result so far.InterpretationThese data provide the most comprehensive analysis of genetic variability in DLB to date. The fact that no novel risk loci have been identified after doubling the cohort size indicates the potentially significant role of rare variants in the genetic architecture of DLB and stresses the urgent need for larger, well-characterized cohorts of this disease for genetic studies. The sex-stratified analysis shows that males and females have different signatures of genetic risk for DLB. These results have widespread implications for clinical practice and clinical trials’ design in DLB.
Published: 2022
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27. Association between LAG3/CD4 gene variants and risk of Parkinson's disease

Author: Elena García‐Martín, Pau Pastor, Javier Gómez‐Tabales, Hortensia Alonso‐Navarro, Ignacio Alvarez, Mariateresa Buongiorno, Maria de las Olas Cerezo‐Arias, Miquel Aguilar, José A. G. Agúndez, and Félix Javier Jiménez‐Jiménez
Subjects: Genotype, Nucleotides, Clinical Biochemistry, Parkinson Disease, General Medicine, Ligands, Polymorphism, Single Nucleotide, Lymphocyte Activation Gene 3 Protein, Biochemistry, Gene Frequency, Antigens, CD, Case-Control Studies, CD4 Antigens, alpha-Synuclein, Humans, Female, Genetic Predisposition to Disease
Abstract: Several recent studies suggest a possible role of lymphocyte activation 3 (LAG3) protein. LAG3 can behave as an α-synuclein ligand, and serum and cerebrospinal fluid-soluble LAG3 levels have been proposed as a marker of Parkinson's disease (PD). In this study, we aimed to investigate whether there is an association between 3 common single-nucleotide variations (SNVs) in the LAG3 gene and its closely related CD4 molecule gene and the risk of PD in a Caucasian Spanish population. Two of them have been previously associated with the risk of PD in Chinese females.We analysed genotypes and allele frequencies for CD4 rs1922452, CD4 951818 and LAG3 rs870849 SNVs, by using specifically designed TaqMan assays, in a cohort composed of 629 PD patients and 865 age- and gender-matched healthy controls.The frequencies of the CD4 rs1922452 A/A genotype, according to the dominant and recessive genetic models, and of the CD4 rs1922452/A allelic variant were significantly lower, and the frequencies of the CD4 rs951818 A/A genotype, according to the dominant genetic model, and of the CD4 rs951818/A allele, were significantly higher in PD patients than in controls. The differences were not significant after stratifying by sex. These two SNVs showed strong linkage. Regression models showed a lack of relation between the 3 SNVs studied and the age at onset of PD.These data suggest a possible role of CD4 rs1922452 and CD4 rs951818 polymorphisms in the risk of PD.
Published: 2022
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28. Mendelian randomization confirms the role of Y-chromosome loss in Alzheimer’s Disease etiopathogenesis in males

Author: Pablo García-González, Itziar de Rojas, Sonia Moreno-Grau, Laura Montrreal, Raquel Puerta, Emilio Alarcón-Martín, Inés Quintela, Adela Orellana, Victor Andrade, Pamela Martino Adami, Stefanie Heilmann-Heimbach, Pilar Gomez-Garre, María Teresa Periñán, Ignacio Alvarez, Monica Diez-Fairen, Raul Nuñez Llaves, Claudia Olivé Roig, Guillermo Garcia-Ribas, Manuel Menéndez-González, Carmen Martínez, Miquel Aguilar, Mariateresa Buongiorno, Emilio Franco-Macías, Maria Eugenia Saez, Amanda Cano, Maria Bullido, Luis Real, Eloy Rodríguez-Rodríguez, Jose Royo, Victoria Álvarez, Pau Pastor, Gerard Piñol-Ripoll, Pablo Mir, Miguel Calero Lara, Miguel Medina Padilla, Pascual Sánchez-Juan, Angel Carracedo, Sergi Valero, Isabel Hernandez, Lluis Tàrraga, Alfredo Ramirez, Mercé Boada, and Agustín Ruiz
Abstract: Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event occurring exclusively in men and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomization to construct an age-independent polygenic risk score of mLOY (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per SD unit (p=4.22·10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in males with mild cognitive impairment (HR=1.23; p=0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group. The male-specificity of the observed effects suggests that these associations of mLOY with AD are caused by the inherent loss of the Y chromosome, and not by the increased genomic instability underlying mLOY risk. Additionally, we found that blood mLOY phenotype was associated with increased CSF levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis. Furthermore, we encourage researchers to use this mloy-PRS instrument to find unbiased associations between mLOY and ageing-related diseases.
Published: 2022
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29. Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia

Author: Montse Ysamat, Ángela Alonso, Monica Diez-Fairen, Miquel Aguilar, Ignacio Alvarez, Juan Pablo Tartari, Britta Brix, Maria Carcel, Philipp Arendt, Jose Manuel González, and Pau Pastor
Subjects: Pathology, medicine.medical_specialty, Amyloid, tau Proteins, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, mental disorders, medicine, Amyloid precursor protein, Humans, Dementia, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive decline, Amyloid beta-Peptides, biology, business.industry, Dementia with Lewy bodies, medicine.disease, Peptide Fragments, Neurology, Frontotemporal Dementia, Positron-Emission Tomography, biology.protein, Neurology (clinical), Alzheimer's disease, business, Biomarkers, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: BACKGROUND AND PURPOSE Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia. METHODS Amyloid-β (Aβ) 1-42, total tau (t-tau), phosphorylated tau, Aβ40 , Aβ38 , beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), neurogranin (ng), phosphorylated neurofilament heavy-chain, and α-synuclein (α-syn) CSF levels were analyzed in 319 subjects, among whom 57 also underwent an amyloid PET scan. We also analyzed longitudinal clinical data from 239 subjects. RESULTS Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels. CONCLUSIONS These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.
Published: 2020
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30. Nuevos datos normativos de la versión española de la Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) forma A

Author: D. Badenes, N. Calzado, N. Cerulla, L. Casas-Hernanz, S. Muntal, Miquel Aguilar, and E. Doval
Subjects: 050103 clinical psychology, Repeatable Battery for the Assessment of Neuropsychological Status, 05 social sciences, Normative data, Spanish-language version, Neuropsychological assessment, lcsh:RC346-429, Developmental psychology, 03 medical and health sciences, 0302 clinical medicine, Form A, Repeatable Battery for the Asessment of Neuropsychological Status, 0501 psychology and cognitive sciences, Neurology (clinical), Cognitive function, Psychology, Humanities, 030217 neurology & neurosurgery, lcsh:Neurology. Diseases of the nervous system
Abstract: Resumen: Introducción: Repeatable Battery for the Asessment of Neuropsychological Status (RBANS) es utilizada habitualmente en la práctica clínica para la evaluación de funciones cognitivas. Se caracteriza por su corta duración, 20-30 minutos de administración, por la ausencia de efecto aprendizaje, dispone de 4 versiones paralelas y por su capacidad discriminativa de diferentes enfermedades.Se presentan datos normativos de la RBANS-E (versión española forma A de la batería) para población española de 20-89 años. Métodos: Seiscientos nueve individuos accedieron a participar. Se les sometió a una valoración previa mediante anamnesis que incluía el Mini Mental State Examination como instrumento de cribado cognitivo y la Blessed Disability Rating Scale como escala funcional. A los 609 sujetos sanos de entre 20 y 89 años de edad se les administró la batería RBANS-E en una sola sesión. Resultados: Los resultados muestran la influencia de la escolaridad en las puntuaciones de todos los subtest. No se observa influencia del género en ninguno de ellos. Conclusiones: Las normas obtenidas aportan datos de gran utilidad clínica para la evaluación cognitiva de población joven y adulta. Abstract: Introduction: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is frequently used in clinical practice to evaluate cognitive function. It is quick to administer (20-30 minutes) and is not influenced by a learning effect. The RBANS includes 4 parallel versions and has a high discriminative ability.Our study provides normative data from the RBANS-E (Spanish-language version of RBANS form A) for a Spanish population aged 20 to 89 years. Methods: The study included 609 subjects aged 20 to 89 years. Participants were evaluated at baseline with a short interview, a cognitive screening test (Mini–Mental State Examination), and a functional scale (Rapid Disability Rating Scale). The RBANS-E was then administered to all 609 participants. Results: Our results show the influence of education on all subtest scores. Sex was observed to have no impact on any subtest. Conclusion: Our study provides highly useful normative data for the cognitive evaluation of young and adult populations.
Published: 2020

31. New normative data from the Spanish-language version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), form A

Author: N. Cerulla, L. Casas-Hernanz, N. Calzado, Miquel Aguilar, E. Doval, D. Badenes, and S. Muntal
Subjects: Cognitive evaluation theory, Repeatable Battery for the Assessment of Neuropsychological Status, Spanish language, medicine.diagnostic_test, Datos normativos, Exploración neuropsicológica, Cognition, Disability Rating Scale, lcsh:RC346-429, Test (assessment), 03 medical and health sciences, 0302 clinical medicine, Repeatable Battery for the Asessment of Neuropsychological Status, medicine, Normative, Versión española, Neuropsychological assessment, Funciones cognitivas, Psychology, Forma A, 030217 neurology & neurosurgery, lcsh:Neurology. Diseases of the nervous system, Clinical psychology
Abstract: Introduction: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is frequently used in clinical practice to evaluate cognitive function. It is quick to administer (20-30 minutes) and is not influenced by a learning effect. The RBANS includes 4 parallel versions and has a high discriminative ability.Our study provides normative data from the RBANS-E (Spanish-language version of RBANS form A) for a Spanish population aged 20-89 years. Methods: The study included 609 subjects aged 20-89 years. Participants were evaluated at baseline with a short interview, a cognitive screening test (Mini–Mental State Examination), and a functional scale (Rapid Disability Rating Scale). The RBANS-E was then administered to all 609 participants. Results: Our results show the influence of education on all subtest scores. Sex was observed to have no impact on any subtest. Conclusion: Our study provides highly useful normative data for the cognitive evaluation of young and adult populations. Resumen: Introducción: Repeatable Battery for the Asessment of Neuropsychological Status (RBANS) es utilizada habitualmente en la práctica clínica para la evaluación de funciones cognitivas. Se caracteriza por su corta duración, 20-30 minutos de administración, por la ausencia de efecto aprendizaje, dispone de 4 versiones paralelas y por su capacidad discriminativa de diferentes enfermedades.Se presentan datos normativos de la RBANS-E (versión española forma A de la batería) para población española de 20-89 años. Métodos: Seiscientos nueve individuos accedieron a participar. Se les sometió a una valoración previa mediante anamnesis que incluía el Mini Mental State Examination como instrumento de cribado cognitivo y la Blessed Disability Rating Scale como escala funcional. A los 609 sujetos sanos de entre 20 y 89 años de edad se les administró la batería RBANS-E en una sola sesión. Resultados: Los resultados muestran la influencia de la escolaridad en las puntuaciones de todos los subtest. No se observa influencia del género en ninguno de ellos. Conclusiones: Las normas obtenidas aportan datos de gran utilidad clínica para la evaluación cognitiva de población joven y adulta.
Published: 2020

32. Constipation Predicts Cognitive Decline in Parkinson's Disease: Results from the COPPADIS Cohort at 2-Year Follow-up and Comparison with a Control Group

Author: Marina Cosgaya, Jose M. Paz González, Esther Cubo, Maria G. Alonso Losada, Nuria López Ariztegui, Isabel González Aramburu, Carmen Borrué, Lydia López Manzanares, Jaime Kulisevsky, Iria Cabo, Julio Dotor García-Soto, Pau Pastor, Carlos Cores Bartolomé, Nuria Caballol, Jessica González Ardura, Lucía García Roca, Berta Solano Vila, Luis M. López Díaz L, Víctor Puente, Pablo Martinez-Martin, Juan García Caldentey, Javier Rúiz Martínez, Lydia Vela, Cristina Martínez Miró, Itziar Gastón, Lucía Naya Ríos, Francisco Carrillo Padilla, Ruben Alonso Redondo, Darrian McAfee, Juan C. Martínez Castrillo, Ines Legarda, Silvia Jesús, Carlos Ordás, Víctor Nogueira, Marta Blázquez Estrada, Oriol de Fábregues, Miquel Aguilar, Hector Canfield, Manuel Seijo, Teresa de Deus Fonticoba, Jorge Hernández Vara, Maria A. Ávila Rivera, Pablo Mir, Pilar Sánchez Alonso, Diego Santos García, Lluis Planellas, Caridad Valero, Monica M. Kurtis, Víctor Gómez Mayordomo, Sonia Escalante, and María Álvarez Sauco
Subjects: medicine.medical_specialty, impairment, Constipation, Parkinson's disease, Non-motor symptoms, Disease, Cellular and Molecular Neuroscience, Cognition, Rating scale, Internal medicine, Cognitive Changes, Medicine, Humans, Cognitive Dysfunction, Cognitive decline, business.industry, Parkinson Disease, constipation, medicine.disease, Control Groups, non-motor symptoms, Impairment, Cohort, Parkinson’s disease, Neurology (clinical), medicine.symptom, business, Follow-Up Studies
Abstract: [Background] Constipation has been linked to cognitive impairment development in Parkinson’s disease (PD). Objective:Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation. Methods:PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson’s Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as “with constipation”. Regression analyses were applied for determining the contribution of constipation in cognitive changes., [Results] At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p, [Conclusion] Constipation is associated with cognitive decline in PD patients but not in controls.
Published: 2022

33. Guia d’abordatge del delírium

Author: Sanchez Garcia, Almudena, Abdelnour, Carla, Giraldo Uribe, Sandra Milena, Robles, Maria José, Pi-Figueras, Maria, Barneto Soto, Matilde, Barberà, Miquel Aguilar, Gual, Neus, Sabartes, Olga, Sales, Pilar, Sabaté Rotés, Anna, Vives, Roser, [Sánchez A, Giraldo M] Grup d’Estudi de Cognició i Conducta, Societat Catalana de Neurologia, Barcelona, Spain. [Abdelnour C, Aguilar M] Grup d’Estudi de Cognició i Conducta, Societat Catalana de Neurologia, Barcelona, Spain. [Robles MJ, Pi-Figueras M, Barneto M, Gual N, Sabartes O, Sales P, Sabaté RA] Societat Catalana de Geriatria i Gerontologia, Barcelona. [Vives R] Gerència de Medicaments, Servei Català de la Salut (CatSalut), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, and Departament de Salut
Subjects: Deliri - Prevenció, enfermedades del sistema nervioso::manifestaciones neurológicas::manifestaciones neuroconductuales::confusión::delirio confusional [ENFERMEDADES], trastornos mentales::trastornos neurocognitivos [PSIQUIATRÍA Y PSICOLOGÍA], Terapèutica, Mental Disorders::Neurocognitive Disorders [PSYCHIATRY AND PSYCHOLOGY], Trastorns de la cognició, terapia, Nervous System Diseases::Neurologic Manifestations::Neurobehavioral Manifestations::Confusion::Delirium [DISEASES]
Abstract: Guia d'abordatge; Delírium; Demències Guía de abordaje; Delirium; Demencias Boarding guide; Delirium; Dementias Aquesta guia pretén ser el punt de referència per a professionals i per a l’entorn cuidador dels pacients amb delírium, alhora que estableix les recomanacions de prevenció, identificació i tractament que garanteixen una atenció òptima per als pacients, de manera que involucra l’entorn cuidador i reconeix la seva importància. L’objectiu d’aquesta guia és la creació d’una eina pràctica i accessible per a tothom que permeti minvar els efectes d’aquesta síndrome (la qual apareix sobtadament), i que sigui útil per a tots els nivells assistencials i per a l’àmbit social.
Published: 2022

34. <scp>COPPADIS</scp> ‐2015 ( <scp>CO</scp> hort of Patients with PArkinson's <scp>DI</scp> sease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation

Author: J.C. Martínez Castrillo, Víctor Puente, J Ruíz Martínez, Esther Cubo, Lluís Planellas, B Solano Vila, Nuria Caballol, J García Caldentey, M Seijo, I González Aramburu, P Sánchez Alonso, O de Fábregues-Boixar, I. Legarda, Pablo Martinez-Martin, C Prieto Jurczynska, Miquel Aguilar, D Santos Garcia, Jaume Kulisevsky, J Hernández Vara, I Gastón, J González Ardura, M J Catalán, M Álvarez Sauco, Iria Cabo, Silvia Jesús, L.M. López Díaz, M Menendez Gonzalez, N López Ariztegui, M G Alonso Losada, C Valero, L. López Manzanares, F Carrillo Padilla, Monica M. Kurtis, S Escalante, M A Ávila Rivera, C Borrué, Lydia Vela, P. Mir, and J M García Moreno
Subjects: medicine.medical_specialty, Parkinson's disease, Impulse control disorder, business.industry, Disease, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Neurology, Quality of life, Internal medicine, Cohort, medicine, Observational study, 030212 general & internal medicine, Neurology (clinical), Prospective cohort study, business, 030217 neurology & neurosurgery, Depression (differential diagnoses)
Abstract: Background and purpose In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). Methods This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. Results In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). Conclusions Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.
Published: 2019
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35. Clinical and genetic characteristics of late-onset Huntington's disease

Author: Oosterloo, Mayke, Bijlsma, Emilia K., van Kuijk, Sander MJ., Minkels, Floor, de Die-Smulders, Christine EM., Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna-Rita, Biunno, Ida, Bonelli, Raphael M., Bronzova, Juliana, Burgunder, Jean-Marc, Dunnett, Stephen B., Ferreira, Joaquim J., Frich, Jan, Giuliano, Joe, Handley, Olivia J., Heiberg, Arvid, Illarioshkin, Sergey, Illmann, Torsten, Klempir, Jiri, Landwehrmeyer, G. Bernhard, Levey, Jamie, Mclean, Tim, Nielsen, Jørgen E., Koivisto, Susana Pro, Päivärinta, Markku, Pålhagen, Sven, Quarrell, Oliver, Ramos-Arroyo, Maria, Roos, Raymund A. C., Saft, Carsten, Sebastián, Ana Rojo, Tabrizi, Sarah J., Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström+, Jan, Zaremba, Jacek (formerly Rödig, Verena, Baake, Barth, Katrin, Garde, Monica Bascuñana, Becanovic, Kristina, Bernard, Tomáš, Betz, Sabrina, Bos, Reineke, Come, Adrien, Guedes, Leonor Correia, Callaghan, Jenny, Capodarca, Selene, Charpentier, Sébastien, Vieira da Silva, Wildson, Di Renzo, Martina, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Genoves, Camille, Gilling, Mette, Horta, Andrea, Hvalstedt, Carina, Held, Christine, Hussain, Hasina, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saul, Mestre, Tiago, Minster, Sara, Monza, Daniela, Münkel, Kristina, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Peppa, Nadia, Rindal, Beate, Rogers, Dawn, Røren (formerly Heinonen), Niini, Salgueiro, Ana, Šašinková, Pavla, Seliverstov, Yury, Taylor, Catherine, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, van Walsem, Marleen R., Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Yudina, Elizaveta, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Hecht, Karen, Herranhof, Brigitte, Holl (formerly Hödl), Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Lilek, Sabine, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Larcher, Barbara, Mahlknecht, Philipp, Müller, Christoph, Pinter, Bernadette, Poewe, Werner, Reiter, Eva-Magdalena, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Ladurner, Gunther, Lilek, Stefan, Sinadinosa, Daniela, Staffen, Wolfgang, Walleczek, Anna Maria, Linder, Christoph, Pirker, Walter, Liessens, Dirk, Calmeyn, Godelinde, Somers, Nele, Delvaux, Isabelle, Boogaerts, Andrea, Flamez, Anja, de Raedt, Sylvie, Alaerts, Nick, Slama, Hichem, Supiot, Frédéric, Constant, Eric, Gillardin, Anne-Françoise, Léonard, Marie-Claude, van de Wyngaerde, Françoise, Dupuis, Michel, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, van Reijen, Dimphna, Weckx, Petra, Kaiserova, Michaela, Šenkárová, Zuzana, Bezdíček, Ondřej, Klempíř, Jiří, Klempířová, Olga, Majerová-Ibarburu, Veronika, Nikolai, Tomáš, Roth, Jan, Stárková, Irena, Madsen, Louise Hasselstrøm, Møller, Anette Torvin, Hjermind, Lena, Jacobsen, Oda, Larsen, Ida Unmack, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Roos, Peter, Stockholm, Jette, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Lolk, Annette, Lundsgaard, Marianne, Wermuth, Lene, Andersson, Christian, Nyberg, Clara, Sundblom, Jimmy, Peippo, Maarit, Sipponen, Marjatta, Bruun, Anu, Hartikainen, Paivi, Mäkipää, Seija, Ollokainen, Mari, Åman, Jaana, Kärppä, Mikko, Ignatius, Jaakko, Jääskeläinen, Outi, Kajula, Outi, Moilanen, Jukka, Mustonen, Aki, Santala, Maire, Eklund, Pia, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Ojala, Marjut, Tähkäpää, Sirkku, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Bled, Déborah, Debruxelles, Sabrina, Duché, Charlotte, Fraisse, Sonia, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Couttier, Julien, Debilly, Bérengère, Delaigue, Christine, Derost, Philippe, Durif, Franck, Germain, Véronique, Legendre, Perrine, Loiseau, Sylvie, Marques, Ana, Ulla, Miguel, Vidal, Tiphaine, Badei, Farideh, Boissé, Marie-Françoise, Boudali, Lotfi, Cleret de Langavant, Laurent, Lemoine, Laurie, Morgado, Graca, Youssov, Katia, Annic, Agnès, Barthélémy, Recka, De Bruycker, Christelle, Cabaret, Maryline, Carette, Anne-Sophie, Carrière, Nicolas, Decorte, Eric, Defebvre, Luc, Delliaux, Marie, Delval, Arnaud, Depelchin, Alizé, Destee, Alain, Dewulf-Pasz, Nelly, Dondaine, Thibaut, Dugauquier, Florence, Dujardin, Kathy, Hopes, Lucie, Krystkowiak, Pierre, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Mutez, Eugénie, Peter, Mireille, Plomhause, Lucie, Sablonnière, Bernard, Simonin, Clémence, Tard, Céline, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Blin, Stéphanie, Chen, Simone, Masmoudi, Kamel, Morin, Gilles, Roussel, Martine, Tir, Mélissa, Schüler, Béatrice, Wannepain, Sandrine, Zouitina, Yassine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Guenam, Aicha, Mundler, Laura, Nguyen, Karine, Benaich, Sandra, Brice, Alexis, Boster, Sarah, Charles, Perrine, Durr, Alexandra, Ewenczyk, Claire, Francisque, Hélène, Jauffret, Céline, Justo, Damian, Kassar, Abdulrahman, Klebe, Stephan, Lesne, Fabien, Milani, Paolo, Monin, Marie-Lorraine, Monnier, Tiffany, Roze, Emmanuel, Tataru, Alina, Tchikviladzé, Maya, Bioux, Sandrine, Bliaux, Evangeline, Girard, Carole, Guyant-Maréchal, Lucie, Hannequin, Didier, Hannier, Véronique, Jourdain, Séverine, Maltête, David, Pouliquen, Dorothée, Anheim, Mathieu, Barun, Nadia, Lagha-Boukbiza, Ouhaid, Longato, Nadine, Marcel, Christophe, Phillipps, Clélie, Rudolf, Gabrielle, Steinmetz, Gisèle, Tranchant, Christine, Wagner, Caroline, Zimmermann, Marie-Agathe, Blondeau, Leily, Calvas, Fabienne, Cheriet, Samia, Delabaere, Helène, Demonet, Jean-François, Marquine, Laurent, Pariente, Jérémie, Pierre, Michèle, Pomies, Elsa, Rolland, Sandrine, Souyris, Corinne, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Beuth, Markus, Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike, Thiel, Silvia, Andrich, Jürgen, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kraus, Peter, Stamm, Christiane, Ganos, Christos, Stubbe, Lars, Tadic, Vera, Tübing, Jennifer, Lange, Herwig, Bosredon, Cecile, Hunger, Ulrike, Löhle, Matthias, Maass, Antonia, Ossig, Christiana, Schmidt, Simone, Storch, Alexander, Wolz, Annett, Wolz, Martin, Kohl, Zacharias, Kozay, Christina, Winkler, Jürgen, Bergmann, Ulrike, Böringer, Regina, Capetian, Philipp, Kammel, Gerit, Lambeck, Johann, Mächtel, Miriam, Meier, Simone, Rijntjes, Michel, Zucker, Birgit, Boelmans, Kai, Goerendt, Ines, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Ribbat+, Michael, Longinus, Bernhard, Möller, Carsten, Bürk, Katrin, Lüsebrink, Antje, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthias, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Vogel, Melanie, Weydt, Patrick, Musacchio, Thomas, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, Difruscolo, Olimpia, Franco, Giovanni, Nuzzi, Angela, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Calandra-Buonaura, Giovanna, Capellari, Sabina, Cortelli, Pietro, Gallassi, Roberto, Poda, Roberto, Scaglione, Cesa, Agosti, Chiara, Barlati, Sergio, Compostella, Silvia, Marchina, Eleonora, Padovani, Alessando, Figorilli, Michela, Marrosu, Francesco, Muroni, Antonella, Piras, Valeria, Vacca, Melisa, Bertini, Elisabetta, Bartoli, Caterina, Fortunato, Fernanda, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, Bandettini di Poggio, Monica, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Di Maria, Emilio, Tamburini, Tiziano, Albanese, Alberto, Castagliuolo, Simona, Castaldo, Anna, Di Donato, Stefano, Di Bella, Daniela, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Panzeri, Marta, Paridi, Dominga, Soliveri, Paola, Spagnolo, Francesca, Taroni, Franco, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Esposito, Chiara, Martino, Tiziana, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Vezza, Maurizio, Squitieri, Ferdinando, D'Alessio, Barbara, Lovo, Francesca, Bentivoglio, Anna Rita, Bove, Francesco, Catalli, Claudio, Di Giacopo, Raffaella, Fasano, Alfonso, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Loria, Giovanna, Modoni, Anna, Petracca, Martina, Piano, Carla, Chiara, Piccininni, Quaranta, Davide, Romano, Silvia, Soleti, Francesco, Solito, Marcella, Spadaro, Maria, Torlizzi, Flavia, Coarelli, Giulia, Ferraldeschi, Michela, Ristori, Giovanni, van Hout, Monique S. E., van Vugt, Jeroen P. P., Marit de Weert, A., Verhoeven, Marloes, Dekker, Meike, Klooster, Jesper, Leenders, Nico, van Oostrom, Joost, Kremer, Berry, Baake, Verena, van den Bogaard, Simon J. A., Dumas, Eve M., t Hart, Ellen P., Hogenboom, Marye, Jacobs, Milou, Jurgens, Caroline, Kampstra, Anne, Schoonderbeek, Anne, Witjes-Ané, Marie-Noëlle, Duits, Annelien, Waber, Mirella, Verstappen, Carla, Blinkenberg, Ellen Økland, Hauge, Erik, Tyvoll, Hilde, Aaserud, Olaf, Aanonsen, Nils Olaf, Bjørgo, Kathrine, Borgerød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan C., Gørvell, Per F., Haggag, Kathrine, Johannessen, Cecilie Haggag, Retterstøl, Lars, Røsby, Oddveig, Rummel, Jutta, Sikiric, Alma, Stokke, Bodil, van Walsem, Marleen, Wehus, Ragnhild, Arntsen, Vibeke, Bjørnevoll, Inga, Sando, Sigrid Botne, Haug, Marte Gjøl, Størseth, Hanna Haugan, Østern, Rune, Paulsen, Julie, Dziadkiewicz, Artur, Konkel, Agnieszka, Narożańska, Ewa, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michał, Błaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Kłodowska – Duda, Gabriela, Opala, Grzegorz, Rudzińska, Monika, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Małgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Stenwak, Agata, Szczudlik, Andrzej, Szczygieł, Elżbieta, Wójcik, Magdalena, Wasielewska, Anna, Anna Bryl, Jacek Anioła, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempołowicz, Justyna, Wiśniewski, Bartłomiej, Gogol (formerly Kalbarczyk), Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski+, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stępniak, Iwona, Sułek, Anna, Zaremba, Jacek, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Almeida, Manuel, Calado, Ana, Dias, Margarida, Morgado, Joana, Semedo, Cristina, Coelho, Miguel, Magalhães, Andreia, Mendes, Tiago, Neutel, Dulce, Rodrigues, Filipe, Valadas, Anabela, Costa, Cristina, Cardoso, Helena, Santos, Mariana, Cação, Gonçalo, Cavaco, Sara, Damásio, Joana, Fernandes, Joana, Gonçalves, Alexandra, Loureiro, Rui, Moreira, Inês, Magalhães, Marina, Salgado, Paula, Andrade, Carlos, Costa, Andreia, Garrett, Carolina, Gago, Miguel, Guimarães, Joana, Massano, João, Meireles, Joana, Monteiro, Ana, Khasanova, Diana, Zalyalova, Zuleykha, Klyushnikov, Sergey, Sidorova, Olga, Smirnov, Oleg, Antonova, Victoria, Kopishinskaya, Svetlana, Korotysh, Maria, Magzhanov, Rim, Saifullina, Elena, Kurbatov, Sergey, Solis, Pilar, Herrera, Carmen Durán, Moreno, Patrocinio Garcia, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Classen, Serge Jaumà, Dedichá, Nadia Rodríguez, Buongiorno, María Teresa, María, Andrés de la Cerda Santa, Muñoz, Esteban, Santacruz, Pilar, Barbera, Miquel Aguilar, Pardo, Sonia Arribas, Guia, Dolors Badenes, Calzado, Noemi, Hernanz, Laura Casas, Tartari Díaz-Zorita, Juan Pablo, Catena, Judit López, Ferrer, Pilar Quiléz, Carruesco, Gemma Tome, Robert, Misericordia Floriach, Viladrich, Cèlia Mareca, Roca, Elvira, Ruiz Idiago, Jesús Miguel, Riballo, Antonio Villa, Campolongo, Antonia, Fernandez de Bobadilla, Ramon, Bojarsky, Jaime Kulisevsky, Pagonabarraga, Javier, Perez, Jesus Perez, Ribosa, Roser, Villa, Carolina, Acera Gil, Maria Angeles, Corrales, Koldo Berganzo, Gomez Esteban, Juan Carlos, González, Amaia, Merino, Beatriz Tijero, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Sánchez, Jesús, Romero, Sandra Gutierrez, Arbelo, José Matías, Malo de Molina, Rocío, Martín, Idaira, Periañez, Juan Manuel, Udaeta, Beatriz, Alonso-Frech, Fernando, Loarte, María del Valle, Barrero, Francisco, Morales, Blas, Frades, Belén, Villanueva, Marina Ávila, Zea Sevilla, Maria Ascension, Fenollar, María del Mar, García-Ramos García, Rocío, Villanueva, Clara, Bascuñana, Mónica, Ventura, Marta Fatás, Caldentey, Juan García, Ribas, Guillermo García, García de Yébenes, Justo, López-Sendón Moreno, José Luis, Barral, Verónica Mañanes, Feliz, Cici, García Ruíz, Pedro José, García, Ana, López, Rosa Guerrero, Bárcenas, Antonio Herranz, Martínez-Descals, Asunción, Pueyo, Angel Martínez, Martin, Veronica Puertas, Martínez, Noelia Rodríguez, Montojo, Teresa, Sainz Artiga, María José, Sánchez, Vicenta, Alarcón, María Dolores, Almagro, Carmen Antúnez, Diéguez, Esther, Fortuna, Lorenza, Legaz, Agustina, Manzanares, Salvadora, Muñoz, Juan Marín, Antequera Torres, María Martirio, Perea, Fuensanta Noguera, Vivancos, Laura, González, Sonia, Guisasola, Luis Menéndez, Prieto, Marta Para, Ribacoba, René, Salvador, Carlos, Lozano, Pablo Sánchez, Ramirez, Inés Legarda, Benito, Dolors Moragues, Arques, Penelope Navas, Lopera, Monica Rodriguez, Pastor, Barbara Vives, Gaston, Itziar, Garcia-Amigot, Fermin, Martinez-Jaurrieta, Maria Dolores, Ramos-Arroyo, Maria Antonia, Adarmes, Astrid, Bernal-Escudero, Maravilla, Carrillo, Fátima, Jesús, Silvia, Mir, Pablo, Vargas-González, Laura, Hermoso, Fátima Damas, García Moreno, José Manuel, Jaramillo, Javier Abril, Lucena, Carolina Mendez, Pacheco Cortegana, Eva María, Peña, José Chacón, Redondo, Luis, Sánchez, Violeta Sánchez, Fernandez, Cristina Melgar, Romero Lemos, María Dolores, Mata, Maite Paredes, Casado, Rocío Villagrán, Bosca, Maria, Burguera, Juan Andres, Brugada, Francisco Castera, Millán Salvador, Jose Maria, Vilaplana, Carmen Peiró, Solís, Pilar, Figuerola, Begoña Jeweinat, Palanca, Paloma Millan, Diago, Elena Bellosta, López del Val, Javier, Martinez, Laura Martinez, López, Elena, Høsterey-Ugander, Ulrika, Fredlund, Gunnel, Constantinescu, Radu, Lewin, Kajsa, Neleborn-Lingefjärd, Liselotte, Berglund, Maria, Berglund, Peter, Linnsand, Petra, Petersén, Åsa, Reimer, Jan, Widner, Håkan, Esmaeilzadeh, Mouna, Tedroff, Joakim, Winnberg, Elisabeth, Benaminov, Stanislav, Björnsson, Elisabeth, Merrick, Daniel, Paucar, Martin, Svenningsson, Per, Wallden, Tina, Berglund, Måns, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Ekwall, Camilla, Göller, Marie-Lousie, Johansson, Anders, Niemelä, Valter, Nyholm, Dag, Wiklund, Leif, Koehli, Jessica, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Zaugg, Sabine Weber, Esposito, Federica, Good, Jean-Marc, Paus, Karin, Vingerhoets, Francois, Wider+, Christian, Jung, Hans H., Petersen, Jens A., Ligon-Auer, Maria, Mihaylova, Violeta, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A., Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Harrower, Timothy, Vernon, Nathan, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza (Keylock), Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Haig-Brown, Diane, Craven, Janet, Pallett, Andrew, Simpson, Steve, Weekes, Rebecca, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Barker, Roger A., O'Keefe, Deidre, Gerrtiz (nee Di Pietro), Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Goudie, David, Buchanan, Lindsay, Mcfadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Carrie, Ho, Mcgill, Marie, Porteous, Mary, Pearson, Pauline, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, Mckenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Neumann, Christian, Patterson, Kirsten, Thomson, David, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Brown, Pauline, Burrows, Liz, Fletcher, Amy, Harding, Alison, Harrison, Kaye, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Rowett, Liz, Andrew, Alyson, Frost, Julie, Noad, Rupert, Cosgrove, Jeremy, Gallantree, Deena, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, Mcentagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Gosling (nee Brown), Stefanie, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thomas, Wild, Edward, Ackermann, Oda, Duport, Sophie, Scott, Adrienne, Stoy, Nicholas, Vaughn, Jenny, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen (formerly Ritchie), Nichola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Fullerton, Neil, Holmes, Katrina, Komati, Suresh, Mcdonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Lois, Singh, Baldev, Wood, Josh, Knight, Caroline, O'Neill, Mari, Purkayastha, Debasish Das, Nemeth, Andrea H., Siuda, Gill, Valentine, Ruth, Dixon, Kathryn, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, Donovan, John O., Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Burn, John, Bailey, Wendy, Coleman, Caroline, Majeed, Tahir, Verstraelen (Ritchie), Nicola, Barrett, Wendy, Aileen, Ho, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Taylor, Cat, Tidswell, Katherine, Kipps, Christopher, Mackinnon, Lesley, Agarwal, Veena, Hayward, Elaine, Gunner, Kerry, Harris, Kayla, Anderson, Mary, Heywood, Melanie, Keys, Liane, Smalley, Sarah, El-Nimr, George, Duffell, Allison, Wood, Sue, Kennedy (nee Smith), Karen, Gowers, Lesley, Powell, Kingsley, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Phillips, Michelle, Tan, Louis, Lau, Puay Ngoh, Pica, Emmanuel, Roos, Raymund AC., Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), MUMC+: KIO Kemta (9), Epidemiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, Klinische Genetica, MUMC+: DA KG Polikliniek (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine
Subjects: Male, HD, 0301 basic medicine, Pediatrics, Neurology, Huntingtin Protein/genetics, FEATURES, Disease, Neuropsychological Tests, 0302 clinical medicine, Cognitive Dysfunction/psychology, Medicine, Family history, Postural Balance, Huntington Disease/genetics, Huntingtin Protein, education.field_of_study, Chorea/physiopathology, Huntington's disease, Sensation Disorders/physiopathology, Middle Aged, Dystonia, Settore MED/26 - NEUROLOGIA, Huntington Disease, neurodegenerative disorders, Sensation Disorders, Disease Progression, Female, medicine.symptom, Adult, medicine.medical_specialty, Population, Age of onset, Late-onset Huntington's disease, Geriatrics and Gerontology, Neurology (clinical), 03 medical and health sciences, AGE, Chorea, Humans, Cognitive Dysfunction, education, Dystonia/physiopathology, Gait Disorders, Neurologic/physiopathology, Gait Disorders, Neurologic, business.industry, medicine.disease, Gait, 030104 developmental biology, Trinucleotide Repeat Expansion, business, 030217 neurology & neurosurgery, Balance problems
Abstract: Background: The frequency of late-onset Huntington's disease (>59 years) is assumed to be low and the clinical course milder. However, previous literature on late-onset disease is scarce and inconclusive. Objective: Our aim is to study clinical characteristics of late-onset compared to common-onset HD patients in a large cohort of HD patients from the Registry database. Methods: Participants with late- and common-onset (30–50 years)were compared for first clinical symptoms, disease progression, CAG repeat size and family history. Participants with a missing CAG repeat size, a repeat size of ≤35 or a UHDRS motor score of ≤5 were excluded. Results: Of 6007 eligible participants, 687 had late-onset (11.4%) and 3216 (53.5%) common-onset HD. Late-onset (n = 577) had significantly more gait and balance problems as first symptom compared to common-onset (n = 2408) (P
Published: 2019
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36. Mood in Parkinson's disease: From early- to late-stage disease

Author: Ángel Aneiros, Ardura J. González, Nuria Caballol, Jurczynska C. Prieto, C Valero, Víctor Nogueira, Silvia Jesús, Pablo Mir, Lluís Planellas, Padilla F. Carrillo, Caldente J. García, I. Legarda, Losada M. G. Alonso, Itziar Gastón, Moreno J. M. García, Miquel Aguilar, Aymerich L. Valdés, Alonso P. Sánchez, Bartolome C. Cores, Vila B. Solano, Darrian McAfee, Lydia Vela, Aramburu I. González, Pau Pastor, Esther Cubo, Castro E. Suárez, Víctor Puente, Ariztegui N. López, Díaz L. López, Castrillo J. C. Martínez, Fonticoba T. De Deus, Diego Santos-García, Rivera M. A. Ávila, Jaime Kulisevsky, C Borrué, Monica M. Kurtis, S Escalante, Vara J. Hernández, Sauco M. Álvarez, Marina Cosgaya, Manzanares L. López, M Seijo, Iria Cabo, Estrada M. Blázquez, Catalán M. José, Martínez J. Rúiz, and Oriol de Fábregues-Boixar
Subjects: Male, medicine.medical_specialty, Parkinson's disease, mood, Disease, Group B, s disease, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Surveys and Questionnaires, Linear regression, Medicine, Humans, Depression (differential diagnoses), Aged, 030214 geriatrics, business.industry, Parkinson Disease, Parkinson&apos, medicine.disease, Health Surveys, Psychiatry and Mental health, Mood, Cross-Sectional Studies, quality of life, Cohort, depression, Quality of Life, Female, Geriatrics and Gerontology, disease duration, business
Abstract: Background Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. Methods PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: = 10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). Results Six hundred and sixty-three PD patients (62.6 +/- 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). Conclusions Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.
Published: 2021

37. Pathogenic huntingtin repeat expansions in patients with frontotemporal dementia and amyotrophic lateral sclerosis

Author: Ramita Dewan, Ruth Chia, Jinhui Ding, Richard A. Hickman, Thor D. Stein, Yevgeniya Abramzon, Sarah Ahmed, Marya S. Sabir, Makayla K. Portley, Arianna Tucci, Kristina Ibáñez, F.N.U. Shankaracharya, Pamela Keagle, Giacomina Rossi, Paola Caroppo, Fabrizio Tagliavini, Maria L. Waldo, Per M. Johansson, Christer F. Nilsson, James B. Rowe, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Edwin Jabbari, Coralie Viollet, Jonathan D. Glass, Andrew B. Singleton, Vincenzo Silani, Owen A. Ross, Mina Ryten, Ali Torkamani, Toshiko Tanaka, Luigi Ferrucci, Susan M. Resnick, Stuart Pickering-Brown, Christopher B. Brady, Neil Kowal, John A. Hardy, Vivianna Van Deerlin, Jean Paul Vonsattel, Matthew B. Harms, Huw R. Morris, Raffaele Ferrari, John E. Landers, Adriano Chiò, J. Raphael Gibbs, Clifton L. Dalgard, Sonja W. Scholz, Bryan J. Traynor, Adelani Adeleye, Camille Alba, Dagmar Bacikova, Daniel N. Hupalo, Elisa McGrath Martinez, Harvey B. Pollard, Gauthaman Sukumar, Anthony R. Soltis, Meila Tuck, Xijun Zhang, Matthew D. Wilkerson, Bradley N. Smith, Nicola Ticozzi, Claudia Fallini, Athina Soragia Gkazi, Simon D. Topp, Jason Kost, Emma L. Scotter, Kevin P. Kenna, Jack W. Miller, Cinzia Tiloca, Caroline Vance, Eric W. Danielson, Claire Troakes, Claudia Colombrita, Safa Al-Sarraj, Elizabeth A. Lewis, Andrew King, Daniela Calini, Viviana Pensato, Barbara Castellotti, Jacqueline de Belleroche, Frank Baas, Anneloor L.M.A. ten Asbroek, Peter C. Sapp, Diane McKenna-Yasek, Russell L. McLaughlin, Meraida Polak, Seneshaw Asress, Jesús Esteban-Pérez, José Luis Muñoz-Blanco, Zorica Stevic, Sandra D’Alfonso, Letizia Mazzini, Giacomo P. Comi, Roberto Del Bo, Mauro Ceroni, Stella Gagliardi, Giorgia Querin, Cinzia Bertolin, Wouter van Rheenen, Frank P. Diekstra, Rosa Rademakers, Marka van Blitterswijk, Kevin B. Boylan, Giuseppe Lauria, Stefano Duga, Stefania Corti, Cristina Cereda, Lucia Corrado, Gianni Sorarù, Kelly L. Williams, Garth A. Nicholson, Ian P. Blair, Claire Leblond-Manry, Guy A. Rouleau, Orla Hardiman, Karen E. Morrison, Jan H. Veldink, Leonard H. van den Berg, Ammar Al-Chalabi, Hardev Pall, Pamela J. Shaw, Martin R. Turner, Kevin Talbot, Franco Taroni, Alberto García-Redondo, Zheyang Wu, Cinzia Gellera, Antonia Ratti, Robert H. Brown, Christopher E. Shaw, John C. Ambrose, Prabhu Arumugam, Emma L. Baple, Marta Bleda, Freya Boardman-Pretty, Jeanne M. Boissiere, Christopher R. Boustred, H. Brittain, Mark J. Caulfield, Georgia C. Chan, Clare E.H. Craig, Louise C. Daugherty, Anna de Burca, Andrew Devereau, Greg Elgar, Rebecca E. Foulger, Tom Fowler, Pedro Furió-Tarí, Joanne M. Hackett, Dina Halai, Angela Hamblin, Shirley Henderson, James E. Holman, Tim J.P. Hubbard, Rob Jackson, Louise J. Jones, Dalia Kasperaviciute, Melis Kayikci, Lea Lahnstein, Kay Lawson, Sarah E.A. Leigh, Ivonne U.S. Leong, Javier F. Lopez, Fiona Maleady-Crowe, Joanne Mason, Ellen M. McDonagh, Loukas Moutsianas, Michael Mueller, Nirupa Murugaesu, Anna C. Need, Chris A. Odhams, Christine Patch, Daniel Perez-Gil, Dimitris Polychronopoulos, John Pullinger, Tahrima Rahim, Augusto Rendon, Pablo Riesgo-Ferreiro, Tim Rogers, Kevin Savage, Kushmita Sawant, Richard H. Scott, Afshan Siddiq, Alexander Sieghart, Damian Smedley, Katherine R. Smith, Alona Sosinsky, William Spooner, Helen E. Stevens, Alexander Stuckey, Razvan Sultana, Ellen R.A. Thomas, Simon R. Thompson, Carolyn Tregidgo, Emma Walsh, Sarah A. Watters, Matthew J. Welland, Eleanor Williams, Katarzyna Witkowska, Suzanne M. Wood, Magdalena Zarowiecki, Sampath Arepalli, Pavan Auluck, Robert H. Baloh, Robert Bowser, Alexis Brice, James Broach, William Camu, John Cooper-Knock, Philippe Corcia, Carsten Drepper, Vivian E. Drory, Travis L. Dunckley, Faraz Faghri, Jennifer Farren, Eva Feldman, Mary Kay Floeter, Pietro Fratta, Glenn Gerhard, Summer B. Gibson, Stephen A. Goutman, Terry D. Heiman-Patterson, Dena G. Hernandez, Ben Hoover, Lilja Jansson, Freya Kamel, Janine Kirby, Neil W. Kowall, Hannu Laaksovirta, Francesco Landi, Isabelle Le Ber, Serge Lumbroso, Daniel JL. MacGowan, Nicholas J. Maragakis, Gabriele Mora, Kevin Mouzat, Liisa Myllykangas, Mike A. Nalls, Richard W. Orrell, Lyle W. Ostrow, Roger Pamphlett, Erik Pioro, Stefan M. Pulst, John M. Ravits, Alan E. Renton, Wim Robberecht, Ian Robey, Ekaterina Rogaeva, Jeffrey D. Rothstein, Michael Sendtner, Katie C. Sidle, Zachary Simmons, David J. Stone, Pentti J. Tienari, John Q. Trojanowski, Juan C. Troncoso, Miko Valori, Philip Van Damme, Ludo Van Den Bosch, Lorne Zinman, Diego Albani, Barbara Borroni, Alessandro Padovani, Amalia Bruni, Jordi Clarimon, Oriol Dols-Icardo, Ignacio Illán-Gala, Alberto Lleó, Adrian Danek, Daniela Galimberti, Elio Scarpini, Maria Serpente, Caroline Graff, Huei-Hsin Chiang, Behzad Khoshnood, Linn Öijerstedt, Christopher M. Morris, Benedetta Nacmias, Sandro Sorbi, Jorgen E. Nielsen, Lynne E. Hjermind, Valeria Novelli, Annibale A. Puca, Pau Pastor, Ignacio Alvarez, Monica Diez-Fairen, Miquel Aguilar, Robert Perneczky, Janine Diehl-Schimd, Mina Rossi, Agustin Ruiz, Mercè Boada, Isabel Hernández, Sonia Moreno-Grau, Johannes C. Schlachetzki, Dag Aarsland, Marilyn S. Albert, Johannes Attems, Matthew J. Barrett, Thomas G. Beach, Lynn M. Bekris, David A. Bennett, Lilah M. Besser, Eileen H. Bigio, Sandra E. Black, Bradley F. Boeve, Ryan C. Bohannan, Francesca Brett, Maura Brunetti, Chad A. Caraway, Jose-Alberto Palma, Andrea Calvo, Antonio Canosa, Dennis Dickson, Charles Duyckaerts, Kelley Faber, Tanis Ferman, Margaret E. Flanagan, Gianluca Floris, Tatiana M. Foroud, Juan Fortea, Ziv Gan-Or, Steve Gentleman, Bernardino Ghetti, Jesse Raphael Gibbs, Alison Goate, David Goldstein, Isabel González-Aramburu, Neill R. Graff-Radford, Angela K. Hodges, Heng-Chen Hu, Daniel Hupalo, Jon Infante, Alex Iranzo, Scott M. Kaiser, Horacio Kaufmann, Julia Keith, Ronald C. Kim, Gregory Klein, Rejko Krüger, Walter Kukull, Amanda Kuzma, Carmen Lage, Suzanne Lesage, James B. Leverenz, Giancarlo Logroscino, Grisel Lopez, Seth Love, Qinwen Mao, Maria Jose Marti, Elisa Martinez-McGrath, Mario Masellis, Eliezer Masliah, Patrick May, Ian McKeith, Marek-Marsel Mesulam, Edwin S. Monuki, Kathy L. Newell, Lucy Norcliffe-Kaufmann, Laura Palmer, Matthew Perkins, Olga Pletnikova, Laura Molina-Porcel, Regina H. Reynolds, Eloy Rodríguez-Rodríguez, Jonathan D. Rohrer, Pascual Sanchez-Juan, Clemens R. Scherzer, Geidy E. Serrano, Vikram Shakkottai, Ellen Sidransky, Nahid Tayebi, Alan J. Thomas, Bension S. Tilley, Ronald L. Walton, Randy Woltjer, Zbigniew K. Wszolek, Georgia Xiromerisiou, Chiara Zecca, Hemali Phatnani, Justin Kwan, Dhruv Sareen, James R. Broach, Ximena Arcila-Londono, Edward B. Lee, Neil A. Shneider, Ernest Fraenkel, Noah Zaitlen, James D. Berry, Andrea Malaspina, Gregory A. Cox, Leslie M. Thompson, Steve Finkbeiner, Efthimios Dardiotis, Timothy M. Miller, Siddharthan Chandran, Suvankar Pal, Eran Hornstein, Daniel J. MacGowan, Terry Heiman-Patterson, Molly G. Hammell, Nikolaos.A. Patsopoulos, Oleg Butovsky, Joshua Dubnau, Avindra Nath, Matt Harms, Eleonora Aronica, Mary Poss, Jennifer Phillips-Cremins, John Crary, Nazem Atassi, Dale J. Lange, Darius J. Adams, Leonidas Stefanis, Marc Gotkine, Suma Babu, Towfique Raj, Sabrina Paganoni, Ophir Shalem, Colin Smith, Bin Zhang, Brent Harris, Iris Broce, Vivian Drory, John Ravits, Corey McMillan, Vilas Menon, Lani Wu, Steven Altschuler, Khaled Amar, Neil Archibald, Oliver Bandmann, Erica Capps, Alistair Church, Jan Coebergh, Alyssa Costantini, Peter Critchley, Boyd CP. Ghosh, Michele T.M. Hu, Christopher Kobylecki, P. Nigel Leigh, Carl Mann, Luke A. Massey, Uma Nath, Nicola Pavese, Dominic Paviour, Jagdish Sharma, Jenny Vaughan, HUS Neurocenter, Neurologian yksikkö, Department of Neurosciences, Clinicum, Pentti Tienari / Principal Investigator, Parkinson's UK, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Pathology, ANS - Cellular & Molecular Mechanisms, AII - Inflammatory diseases, Universidad de Cantabria, Rowe, James [0000-0001-7216-8679], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Huntington's Disease, Pathology, amyotrophic lateral sclerosis, Huntingtin, Neurology, 1702 Cognitive Sciences, International ALS/FTD Genomics Consortium, Neurodegenerative, frontotemporal dementia, 3124 Neurology and psychiatry, 0302 clinical medicine, Medicine, 2.1 Biological and endogenous factors, Psychology, Amyotrophic lateral sclerosis, Aetiology, Alzheimer's Disease Related Dementias (ADRD), NYGC ALS Consortium, Huntingtin Protein, DNA Repeat Expansion, General Neuroscience, Frontotemporal Dementia (FTD), International FTD Genetics Consortium, whole-genome sequencing, Frontotemporal Dementia, Neurological, Cognitive Sciences, Lewy body dementia, huntingtin, repeat expansions, Amyotrophic Lateral Sclerosis, Humans, Mutation, Whole Genome Sequencing, Frontotemporal dementia, Huntington’s disease, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, FALS Sequencing Consortium, Article, 03 medical and health sciences, Atrophy, Rare Diseases, American Genome Center, Clinical Research, mental disorders, Genetics, Acquired Cognitive Impairment, Dementia, PROSPECT Consortium, Neurology & Neurosurgery, Lewy body, business.industry, International LBD Genomics Consortium, Neurosciences, 3112 Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), nutritional and metabolic diseases, medicine.disease, Brain Disorders, nervous system diseases, 030104 developmental biology, Genomics England Research Consortium, 1701 Psychology, ALS, business, 1109 Neurosciences, 030217 neurology & neurosurgery
Abstract: Hannu Laaksovirta konsortion jäsenenä. The Genomics England Research Consortium, The International ALS/FTD Genomics Consortium (iAFGC), The International FTD Genetics Consortium (IFGC), The International LBD Genomics Consortium (iLBDGC), The NYGC ALS Consortium, The PROSPECT Consortium,17 James B. Rowe,17 Luisa Benussi,18 Giuliano Binetti,18,19 Roberta Ghidoni,18 Edwin Jabbari,20,21 Coralie Viollet,22 Jonathan D. Glass,23 Andrew B. Singleton,24 Vincenzo Silani,25,26 Owen A. Ross,27 Mina Ryten,8,28,29 Ali Torkamani,30 Toshiko Tanaka,31 Luigi Ferrucci,31 Susan M. Resnick,32 We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40?64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington?s disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered. We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40?64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington?s disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
Published: 2020
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38. Validity and sensitivity of instrumented postural and gait assessment using low-cost devices in Parkinson's disease

Author: Roberto Llorens, Jorge Latorre, Pau Pastor, Miquel Aguilar, and Ignacio Alvarez
Subjects: Male, 030506 rehabilitation, medicine.medical_specialty, Parkinson's disease, Neurology, Posture, Health Informatics, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Gait (human), Wii balance board, TEORIA DE LA SEÑAL Y COMUNICACIONES, medicine, Humans, Sensitivity (control systems), Postural Balance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Gait, Gait Disorders, Neurologic, Aged, Balance (ability), Kinect, business.industry, Research, Tinetti test, Rehabilitation, Parkinson Disease, Middle Aged, medicine.disease, Convergent validity, Gait analysis, Parkinson’s disease, Female, Gait Analysis, 0305 other medical science, business, human activities, 030217 neurology & neurosurgery
Abstract: [EN] Background Accurate assessment of balance and gait is necessary to monitor the clinical progress of Parkinson's disease (PD). Conventional clinical scales can be biased and have limited accuracy. Novel interactive devices are potentially useful to detect subtle posture or gait-related impairments. Methods Posturographic and single and dual-task gait assessments were performed to 54 individuals with PD and 43 healthy controls with the Wii Balance Board and the Kinect v2 and the, respectively. Individuals with PD were also assessed with the Tinetti Performance Oriented Mobility Assessment, the Functional Gait Assessment and the 10-m Walking Test. The influence of demographic and clinical variables on the performance in the instrumented posturographic and gait tests, the sensitivity of these tests to the clinical condition and phenotypes, and their convergent validity with clinical scales were investigated. Results Individuals with PD in H&Y I and I.5 stages showed similar performance to controls. The greatest differences in posture and gait were found between subjects in H&Y II.5 and H&Y I-I.5 stage, as well as controls. Dual-tasking enhanced the differences among all groups in gait parameters. Akinetic/rigid phenotype showed worse postural control and gait than other phenotypes. High significant correlations were found between the limits of stability and most of gait parameters with the clinical scales. Conclusions Low-cost devices showed potential to objectively quantify posture and gait in established PD (H&Y >= II). Dual-tasking gait evaluation was more sensitive to detect differences among PD stages and compared to controls than free gait. Gait and posture were more impaired in akinetic/rigid PD., This study has been funded by project VALORA, Grant 201701-10 of the Fundacio la Marato de la TV3 (Barcelona, Spain) and the European Union through the Operational Program of the European Regional Development Fund (ERDF) of the Valencian Community 2014-2020 (IDIFEDER/2018/029) to RL, and Alter Laboratories SA to PP.
Published: 2020

39. Genome-wide association, Mendelian Randomization and polygenic risk score studies converge on a role of β−amyloid and APOE locus in Parkinson disease

Author: Laura Ibanez, Kristy Bergmann, Miquel Aguilar, Niger Cairns, Chengran Yang, Joel S. Perlmutter, Umber Dube, Rebecca C. Miller, Pau Pastor, Albert A Davis, Meghan C. Campbell, Jorge A. Bahena, Paul T. Kotzbauer, Ignacio Alvarez, Richard J. Perrin, John O'Donnell, John P. Budde, Oscar Harari, Carol Brenner-Webster, Monica Diez-Fairen, Bruno A. Benitez, Fabiana Geraldo Farias, Carlos Cruchaga, Herve Rhinn, and John C. Morris
Subjects: Oncology, Apolipoprotein E, medicine.medical_specialty, business.industry, Genome-wide association study, Quantitative trait locus, medicine.disease, chemistry.chemical_compound, chemistry, Internal medicine, Mendelian randomization, Medicine, Alzheimer's disease, Allele, business, Pittsburgh compound B, Genetic association
Abstract: Alpha-Synuclein (α-Syn) is the main protein component of Lewy bodies (LB), the pathological hallmark of Parkinson’s disease (PD). Cerebrospinal fluid (CSF) levels of α-Syn are not currently used as a clinical biomarker but may be a proxy for pathological α-Syn accumulation in the brain. Therefore, identifying genetic modifiers of CSF α-Syn levels could provide insights into the underlying molecular mechanisms leading to PD. However, genetic modifiers of CSF α-Syn levels remain unknown. CSF levels of amyloid beta1-42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau181) are standard biomarkers for the diagnosis of Alzheimer disease (AD); its use as quantitative traits in genetic studies have provided novel insights into AD pathophysiology. A systematic study of the genomic architecture of CSF biomarkers in PD has not been conducted. Here, genome-wide association studies (GWAS) were performed using CSF biomarker levels as quantitative traits in four PD cases and control cohorts (combined N=1,960). CSF biomarker (α-Syn, Aβ42, t-tau, and p-tau181) levels were significantly lower in PD cases compared with controls. An SNP, proxy for APOE ε4, was associated with CSF Aβ42 levels (effect=-0.5, p=9.2×10−19). Several genome-wide suggestive loci associated with CSF α-Syn, t-tau, or p-tau181 were found. Polygenic risk scores (PRS) were constructed using the latest PD risk meta-analysis (49,731 PD cases and 784,343 controls) and the largest CSF biomarkers GWAS (N=3,146). PRS calculated using META-PD were associated with PD status in the four cohorts included in the present study (p= 2.2×10−16). A highly significant correlation (Nagelkerke pseudo-R2 =2.29%; p=2.5×10−11) of the genomic architecture between CSF Aβ42 and PD risk was also found. Higher PRS scores were associated with lower CSF Aβ42 levels (p=7.3×10−04). Two-sample Mendelian Randomization (MR) approach revealed that CSF Aβ42 plays a role in PD risk (p=1.4×10−05) and age at onset (p=7.6×10−06), an effect mainly mediated by variants in the APOE locus. Subsequently, the APOE ε4 allele was associated with significantly lower levels of CSF Aβ42 (p=3.8×10−06), higher mean cortical binding potentials (cortical binding of Pittsburgh compound B PET) (p=5.8×10−08) and higher Braak Aβ score (p=4.4×10−04) in PD participants. Together these results from high-throughput and hypothesis-free approaches (GWAS, PRS and MR) converge on a genetic link between PD with CSF Aβ42 and APOE.
Published: 2020
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40. Association between the missense alcohol dehydrogenase rs1229984T variant with the risk for Parkinson’s disease in women

Author: Monica Diez-Fairen, Miquel Aguilar, Pau Pastor, José A. G. Agúndez, Javier Gómez-Tabales, Ignacio Alvarez, Elena García-Martín, Hortensia Alonso-Navarro, Maria Carcel, and Félix Javier Jiménez-Jiménez
Subjects: Adult, Male, Risk, medicine.medical_specialty, Alcohol Drinking, Mutation, Missense, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Gastroenterology, Loss of heterozygosity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genotype, medicine, Humans, Missense mutation, 030212 general & internal medicine, Allele, Allele frequency, Aged, Aged, 80 and over, business.industry, Alcohol Dehydrogenase, ADH1B, Parkinson Disease, Middle Aged, Neurology, Spain, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Several meta-analyses including retrospective case–control studies have shown that the risk of developing Parkinson’s disease (PD) correlates inversely with alcohol consumption and (PD), although the results of prospective longitudinal studies are far from being conclusive. The reasons for this inverse association are not well-known. Because alcohol dehydrogenase is one of the most important alcohol-detoxification enzymes, we tried to replicate a putative association of the risk of developing PD with two missense gene variations affecting the alcohol dehydrogenase 1B (ADH1B) gene (one of them related with aversive effects to alcohol). In a cohort composed of 629 PD patients and 865 age- and gender-matched healthy individuals, we analyzed genotypes and allele frequencies for two common missense ADH1B single nucleotide polymorphisms (SNPs), namely rs1229984 (His48Arg) and rs6413413 (Thr60Ser) using specifically designed TaqMan assays. The frequency of individuals carrying rs1229984T alleles in homozygosity or in heterozygosity was higher in PD than in controls in the whole study cohort (P
Published: 2018
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41. Systematic Screening of Ubiquitin/p62 Aggregates in Cerebellar Cortex Expands the Neuropathological Phenotype of the C9orf72 Expansion Mutation

Author: Isabel Hernández, Miquel Aguilar, Jordi Clarimón, Consuelo Almenar, Anna Antonell, Veronica Santiago-Valera, Sara Charif, Dolores Lopez-Villegas, Pau Pastor, Albert Lladó, Ellen Gelpi, Rainiero Ávila-Polo, Ricardo Rojas-García, Oscar Ramos-Campoy, Oriol Grau-Rivera, Raquel Sánchez-Valle, Julie van der Zee, and Lorena Bajo
Subjects: Male, 0301 basic medicine, Pathology, Cytoplasmic inclusion, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Ubiquitin, C9orf72, Cerebellum, Prospective Studies, Amyotrophic lateral sclerosis, Aged, 80 and over, C9RANT, Mutation, General Medicine, Frontotemporal lobar degeneration, Middle Aged, Phenotype, Fenotip, Neurology, Cerebellar cortex, Female, Adult, medicine.medical_specialty, Biology, Pathology and Forensic Medicine, Cerebellar Cortex, Protein Aggregates, 03 medical and health sciences, Cellular and Molecular Neuroscience, mental disorders, medicine, Humans, Dentate gyrus, Genetic Testing, Aged, Retrospective Studies, C9orf72 Protein, medicine.disease, 030104 developmental biology, biology.protein, Human medicine, Neurology (clinical), Esclerosi lateral amiotròfica, 030217 neurology & neurosurgery
Abstract: The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI). Positive cases were also stained for dipeptide repeats. We identified a total of 21 donors with UPPI and in all of them the C9orf72 hexanucleotide expansion was genetically confirmed. Most donors had an FTLD or to a lesser extent ALS clinico-pathological phenotype. However, 3 cases had been previously classified as having clinically and neuropathologically Lewy body disease. Other co-existing pathologies, especially of the PART-type, were also frequently encountered. This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.
Published: 2018
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42. Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression

Author: Lluís Planellas, L. López Manzanares, M G Alonso Losada, L Valdés Aymerich, J González Ardura, C Valero, C Cores Bartolomé, J Ruíz Martínez, Miquel Aguilar, J García Caldentey, I Gastón, M A Ávila Rivera, C Borrué, T de Deus Fonticoba, I Cabo López, Lydia Vela, C Prieto Jurczynska, E Suárez Castro, Nuria Caballol, M. Blázquez Estrada, M Álvarez Sauco, M J Feal Panceiras, Aaron Diaz, L.M. López Díaz, M J Catalán, M Seijo, Diego Santos-García, Silvia Jesús, J.C. Martínez Castrillo, Monica M. Kurtis, Berta Pascual-Sedano, Pablo Martinez-Martin, P. Mir, N López Ariztegui, J M Paz González, Esther Cubo, P Sánchez Alonso, J M García Moreno, and I. Legarda
Subjects: Quality of life, medicine.medical_specialty, Parkinson's disease, Non-motor symptoms, Disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Surveys and Questionnaires, Mood, medicine, Humans, In patient, 030212 general & internal medicine, Depression (differential diagnoses), Fatigue, business.industry, Depression, Parkinson Disease, medicine.disease, humanities, Neurology, Cohort, Quality of Life, Non motor, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. Material and methods: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. Results: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 +/- 12.8 vs 11.6 +/- 10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 +/- 0.5 vs 4 +/- 0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 +/- 32 vs 29.1 +/- 25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. Conclusions: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.
Published: 2020

43. Caregiver burden in Parkinsonʼs disease

Author: Martínez-Martín, Pablo, Forjaz, Maria João, Frades-Payo, Belén, Rusiñol, Angels Bayés, Fernández-García, José Manuel, Benito-León, Julián, Arillo, Víctor Campos, Barberá, Miquel Aguilar, Sordo, Margarita Pondal, and Catalán, María José
Published: 2007
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44. Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Author: Mcnulty, Paul, Pilcher, Richard, Ramesh, Raviram, Necuiniate, Renata, Hughes, Alis, Farewell, Daniel, Holmans, Peter, Jones, Lesley, Bonelli, Raphael M., Hecht, Karen, Herranhof, Brigitte, Holl, Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Lilek, Sabine, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Larcher, Barbara, Mahlknecht, Philipp, Müller, Christoph, Pinter, Bernadette, Poewe, Werner, Reiter, Eva-Magdalena, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Ladurner, Gunther, Lilek, Stefan, Sinadinosa, Daniela, Staffen, Wolfgang, Walleczek, Anna Maria, Constant, Eric, Gillardin, Anne-Françoise, Léonard, Marie-Claude, Verellen-Dumoulin, Christine, Van De Wyngaerde, Françoise, Dupuis, Michel, Minet, Cécile, Ribaï, Pascale, Van Paemel, Dominique, Boogaerts, Andrea, Vandenberghe, Wim, Van Reijen, Dimphna, Kaiserova, Michaela, Šenkárová, Zuzana, Klempíř, Jiří, Majerová, Veronika, Roth, Jan, Madsen, Louise Hasselstrøm, Møller, Anette Torvin, Hjermind, Lena, Jacobsen, Oda, Lindquist, Suzanne, Nielsen, Jørgen, Regeur, Lisbeth, Stockholm, Jette, Larsen, Ida Unmack, Vangsted-Hansen, Christina, Vinther-Jensen, Tua, Lolk, Annette, Lundsgaard, Marianne, Wermuth, Lene, Andersson, Christian, Nyberg, Clara, Sundblom, Jimmy, Peippo, Maarit, Sipponen, Marjett, Hartikainen, Paivi, Ollokainen, Mari, Åman, Jaana, Ignatius, Jaakko, Kärppä, Mikko, Mustonen, Aki, Kajula, Outi, Jääskalainen, Outi, Moilanen, Jukka, Santala, Maire, Eklund, Pia, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prouzet, Julie, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duché, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Couttier, Julien, Debilly, Bérengère, Delaigue, Christine, Durif, Franck, Legendre, Perrine, Loiseau, Sylvie, Ulla, Miguel, Vidal, Tiphaine, Bachoud-Lévi, Anne-Catherine, Badei, Farideh, Boissé, Marie-Françoise, Boudali, Lotfi, De Langavant, Laurent Cleret, Lemoine, Laurie, Morgado, Graca, Youssov, Katia, Annic, Agnès, Barthélémy, Recka, De Bruycker, Christelle, Cabaret, Maryline, Carette, Anne-Sophie, Carrière, Nicolas, Decorte, Eric, Defebvre, Luc, Delliaux, Marie, Delval, Arnaud, Depelchin, Alizé, Destee, Alain, Dewulf-Pasz, Nelly, Dondaine, Thibaut, Dugauquier, Florence, Dujardin, Kathy, Hopes, Lucie, Krystkowiak, Pierre, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Mutez, Eugénie, Peter, Mireille, Plomhause, Lucie, Sablonnière, Bernard, Simonin, Clémence, Tard, Céline, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Benoit, Alexandra, Berrisoul, Hassan, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Flament, Mélanie, Godefroy, Olivier, Mantaux, Béatrice, Playe, Alicia, Roussel, Martine, Tir, Mélissa, Schüler, Béatrice, Wannepain, Sandrine, Azulay, Jean-Philippe, Chabot, Christelle, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Grosjean, Hélène, Mundler, Laura, Nowak, Marielle, Raseta, Rolland, Benaich, Sandra, Brice, Alexis, Charles, Perrine, Durr, Alexandra, Ewenczyk, Claire, Francisque, Hélène, Jauffret, Céline, Justo, Damian, Kassar, Abdulrahman, Klebe, Stephan, Lesne, Fabien, Milani, Paolo, Monin, Marie-Lorraine, Roze, Emmanuel, Tataru, Alina, Tchikviladzé, Maya, Bioux, Sandrine, Bliaux, Evangeline, Girard, Carole, Guyant-Maréchal, Lucie, Hannequin, Didier, Hannier, Véronique, Jourdain, Séverine, Maltête, David, Pouliquen, Dorothée, Lagha-Boukbiza, Ouhaid, Longato, Nadine, Marcel, Christophe, Phillipps, Clélie, Rudolf, Gabrielle, Steinmetz, Giséle, Tranchant, Christine, Wagner, Caroline, Zimmermann, Marie-Agathe, Blondeau, Leily, Calvas, Fabienne, Cheriet, Samia, Delabaere, Helène, Demonet, Jean-François, Pariente, Jérémie, Pierre, Michèle, Rolland, Sandrine, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Beuth, Markus, Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike, Thiel, Silvia, Andrich, Jürgen, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kraus, Peter, Saft, Carsten, Stamm, Christiane, Lange, Herwig, Maiwald, Robert, Bosredon, Cecile, Hunger, Ulrike, Löhle, Matthias, Maass, Antonia, Ossig, Christiana, Schmidt, Simone, Storch, Alexander, Wolz, Annett, Wolz, Martin, Kohl, Zacharias, Kozay, Christina, Winkler, Jürgen, Bergmann, Ulrike, Böringer, Regina, Capetian, Philipp, Kammel, Gerit, Lambeck, Johann, Mächtel, Miriam, Meier, Simone, Rijntjes, Michel, Zucker, Birgit, Boelmans, Kai, Ganos, Christos, Goerendt, Ines, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Orth, Michael, Schmalfeld, Jenny, Stubbe, Lars, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Francis, Flverly, Gayde-Stephan, Sabine, Gorzolla, Heike, Kramer, Bianca, Minschke, Rebecca, Schrader, Christoph, Tacik, Pawel, Ribbat, Michael, Longinus, Bernhard, Lüsebrink, Antje, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Göpfert, Nicole, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Nathalia, Bachmeier, Michael, Dose, Matthias, Hofstetter, Nina, Marquard, Ralf, Mühlbäck, Alzbeta, Barth, Katrin, Buck, Andrea, Connemann, Julia, Ecker, Daniel, Geitner, Carolin, Held, Christine, Kesse, Andrea, Landwehrmeyer, Bernhard, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süssmuth, Sigurd, Trautmann, Sonja, Vogel, Melanie, Weydt, Patrick, Musacchio, Thomas, Leypold, Christine, Nöth, Kerstin, Cormio, Claudia, Difruscolo, Olimpia, Franco, Giovanni, Sciruicchio, Vittorio, Serpino, Claudia, De Tommaso, Marina, Calandra-Buonaura, Giovanna, Capellari, Sabina, Cortelli, Pietro, Gallassi, Roberto, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, DI Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, DI Maria, Emilio, Albanese, Alberto, Castagliuolo, Simona, Castaldo, Anna, DI Donato, Stefano, DI Bella, Daniela, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Monza, Daniela, Nanetti, Lorenzo, Panzeri, Marta, Paridi, Dominga, Soliveri, Paola, Spagnolo, Francesca, Taroni, Franco, Tomasello, Chiara, De Michele, Giuseppe, DI Maio, Luigi, Rinaldi, Carlo, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Tucci, Tecla, Cannella, Milena, Codella, Valentina, De Gregorio, Francesca, De Nicola, Annunziata, Elifani, Francesca, Martino, Tiziana, Mazzante, Irene, Petrollini, Martina, Simonelli, Maria, Vezza, Maurizio, Squitieri, Ferdinando, Lovo, Francesca, Bentivoglio, Anna Rita, Bove, Francesco, Catalli, Claudio, DI Giacopo, Raffaella, Fasano, Alfonso, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Loria, Giovanna, Modoni, Anna, Petracca, Martina, Piano, Carla, Piccininni, Chiara, Quaranta, Davide, Romano, Silvia, Soleti, Francesco, Solito, Marcella, Spadaro, Maria, Torlizzi, Flavia, Zinzi, Paola, Coarelli, Giulia, Ferraldeschi, Michela, Ristori, Giovanni, Van Hout, Monique S. E., Van Vugt, Jeroen P. P., De Weert, A. Marit, Verhoeven, Marloes, Dekker, Meike, Leenders, Nico, Van Oostrom, Joost, Klooster, Jesper, Kremer, Berry, Baake, Verena, Van Den Bogaard, Simon J. A., Bos, Reineke, Dumas, Eve M., Hart'T, Ellen P., Kampstra, Anne, Roos, Raymund A. 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Marit, Verhoeven, Marloe, Dekker, Meike, Leenders, Nico, Van Oostrom, Joost, Klooster, Jesper, Kremer, Berry, Baake, Verena, Van Den Bogaard, Simon J.A., Bos, Reineke, Dumas, Eve M., Hart't, Ellen P., Kampstra, Anne, Roos, Raymund A.C., Schoonderbeek, Anne, Duits, Annelien, Oosterloo, Mayke, Waber, Mirella, Verstappen, Carla, Blinkenberg, Ellen Økland, Hauge, Erik, Tyvoll, Hilde, Aaserud, Olaf, Bjørgo, Kathrine, Borgeød, Nancy, Dramstad, Elisabeth, Fannemel, Madeleine, Frich, Jan C., Gørvell, Per F., Heiberg, Arvid, Retterstøl, Lar, Røsby, Oddveig, Sikiric, Alma, Stokke, Bodil, Van Walsem, Marleen, Wehus, Ragnhild, Bjørnevoll, Inga, Sando, Sigrid Botne, Haug, Marte Gjøl, Størseth, Hanna Haugan, Arntsen, Vibeke, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Arkuszewski, Michal, Blaszczyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasińska-Myga, Barbara, Kaczmarczyk, Aleksandra, Klodowska-Duda, Gabriela, Opala, Grzegorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Boćwińska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Grabska, Natalia, Krawczyk, Malgorzata, Kubowicz, Ewelina, Malec-Litwinowicz, Michalina, Rudzińska, Monika, Stenwak, Agata, Szczudlik, Andrzej, Szczygiel, Elzbieta, Wójcik, Magdalena, Wasielewska, Anna, Aniola, Jacek, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Wiśniewski, Bartlomiej, Zielonka, Daniel, Gogol, Anna, Janik, Piotr, Jamrozik, Zygmunt, Kaminska, Anna, Kwiecinski, Hubert, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stȩpniak, Iwona, Sulek, Anna, Witkowski, Grzegorz, Zaremba, Jacek, Zdzienicka, Elzbieta, Ziora-Jakutowicz, Karolina, Januário, Cristina, Júlio, Filipa, Almeida, Manuel, Calado, Ana, DIas, Margarida, Morgado, Joana, Semedo, Cristina, Guedes, Leonor Correia, Coelho, Miguel, Ferreira, Joaquim J, Mestre, Tiago, Mendes, Tiago, Valadas, Anabela, Costa, Cristina, Cardoso, Helena, Andrade, Carlo, Costa, Andreia, Garrett, Carolina, Gago, Miguel, Guimarães, Joana, Massano, João, Meireles, Joana, Monteiro, Ana, Herrera, Carmen Durán, Moreno, Patrocinio Garcia, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Classen, Serge Jaumá, Dedichá, Nadia Rodríguez, Buongiorno, María Teresa, De La Cerda Santa María, André, Muñoz, Esteban, Santacruz, Pilar, Barbera, Miquel Aguilar, Sebastián, Ana Rojo, Pardo, Sonia Arriba, Guia, Dolors Badene, Calzado, Noemi, Hernanz, Laura Casa, DÍaz-Zorita, Juan Pablo Tartari, Catena, Judit López, Ferrer, Pilar Quiléz, Carruesco, Gemma Tome, Robert, Misericordia Floriach, Viladrich, Cèlia Mareca, Roca, Elvira, Idiago, Jesús Miguel Ruiz, Villa Riballo, Antonio, Campolongo, Antonia, De Bobadilla, Ramon Fernandez, Bojarsky, Jaime Kulisevsky, Martinez-Horta, Saul, Pagonabarraga, Javier, Perez, Jesus Perez, Ribosa, Roser, Villa, Carolina, Angeles, Maria, Gil, Acera, Corrales, Koldo Berganzo, Esteban, Juan Carlos Gomez, González, Amaia, Merino, Beatriz Tijero, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Romero, Sandra Gutierrez, Arbelo, José Matía, De Molina, Rocío Malo, Martín, Idaira, Periañez, Juan Manuel, Udaeta, Beatriz, Alonso-Frech, Fernando, Del Valle Loarte, María, Barrero, Francisco, Morales, Bla, Frades, Belén, Villanueva, Marina Ávila, Sevilla, Maria Ascension Zea, Frech, Fernando Alonso, Del Mar Fenollar, María, García, Rocío García-Ramo, Villanueva, Clara, Garde, Mónica Bascuñana, Ventura, Marta Fatá, Caldentey, Juan García, Ribas, Guillermo García, De Yébenes, Justo García, Moreno, José Luis López-Sendón, Barral, Verónica Mañane, Cubillo, Patricia Trigo, Ruíz, Pedro José García, García, Ana, López, Rosa Guerrero, Bárcenas, Antonio Herranz, Martínez-Descals, Asunción, Martin, Veronica Puerta, Martínez, Noelia Rodríguez, Artiga, María José Sainz, Sánchez, Vicenta, Pueyo, Angel Martínez, Alarcón, Moreau María Dolore, Almagro, Carmen Antúnez, DIéguez, Esther, Fortuna, Lorenza, Manzanares, Salvadora, Muñoz, Juan Marín, Torres, María Martirio Antequera, Perea, Fuensanta Noguera, Vivancos, Laura, González, Sonia, Guisasola, Luis Menéndez, Prieto, Marta Para, Ribacoba, René, Salvador, Carlo, Lozano, Pablo Sánchez, Ramirez, Inés Legarda, Arques, Penelope Nava, Lopera, Monica Rodriguez, Pastor, Barbara Vive, Gaston, Itziar, Garcia-Amigot, Fermin, Martinez-Jaurrieta, Maria Dolore, Ramos-Arroyo, Maria Antonia, Carrillo, Fátima, Redondo, María Teresa Cácere, Mir, Pablo, González, Laura Varga, Hermoso, Fátima Dama, Moreno, Jose Manuel García, Lucena, Carolina Mendez, Cortegana, Eva María Pacheco, Peña, José Chacón, Redondo, Lui, Sánchez, Violeta Sánchez, Fernandez, Cristina Melgar, Lemos, María Dolores Romero, Mata, Maite Parede, Casado, Rocío Villagrán, Bosca, Maria, Burguera, Juan Andre, Brugada, Francisco Castera, Vilaplana, Carmen Peiró, Solís, Pilar, Figuerola, Begoña Jeweinat, Palanca, Paloma Millan, Wahlström, Jan, Høsterey-Ugander, Ulrika, Fredlund, Gunnel, Constantinescu, Radu, Neleborn-Lingefjärd, Liselotte, Berglund, Maria, Berglund, Peter, Linnsand, Petra, Björnsson, Elisabeth, Paucar, Martin, Pålhagen, Sven, Svenningsson, Per, Wallden, Tina, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Ekwall, Camilla, Göller, Marie-Lousie, Burgunder, Jean-Marc, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Zaugg, Sabine Weber, Esposito, Federica, Good, Jean-Marc, Paus, Karin, Vingerhoets, Francoi, Wider, Christian, Jung, Hans H., Petersen, Jens A., Ligon-Auer, Maria, Mihaylova, Violeta, Downie, Lorna, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Harrower, Timothy, Vernon, Nathan, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, De Souza Keylock, Jenny, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Hayward, Beverley, Sieradzan, Kasia, Wright, Abigail, Barker, Roger A., O'Keefe, Deidre, DI Pietro, Anna Gerrtiz, Fisher, Kate, Goodman, Anna, Hill, Susan, Mason, Sarah, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Dunnett, Stephen, Clenaghan, Catherine, Fullam, Ruth, Hunt, Sarah, Jones, Una, Khalil, Hanan, Minster, Sara, Owen, Michael, Price, Kathleen, Townhill, Jenny, Rosser, Anne, Goudie, David, Buchanan, Lindsay, McFadyen, Paula, Tonner, Alison, Taylor, Anne-Marie, Edwards, Maureen, Ho, Carrie, McGill, Marie, Porteous, Mary, Pearson, Pauline, Irvine, Sarah, Brockie, Peter, Foster, Jillian, Johns, Nicola, McKenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Deith, Catherine, Ireland, Jane, Ritchie, Stuart, Burrows, Liz, Fletcher, Amy, Harding, Alison, Laver, Fiona, Silva, Mark, Thomson, Aileen, Chu, Carol, Evans, Carole, Gallentree, Deena, Hamer, Stephanie, Kraus, Alison, Markova, Ivana, Raman, Ashok, Andrew, Alyson, Frost, Julie, Noad, Rupert, Hobson, Emma, Jamieson, Stuart, Longthorpe, Mandy, Musgrave, Hannah, Peacy, Caroline, Rowett, Liz, Toscano, Jean, Wild, Sue, Yardumian, Pam, Clayton, Carole, DIpple, Heather, Freire-Patino, Dawn, Hallam, Caroline, Middleton, Julia, Alusi, Sundu, Davies, Rhy, Foy, Kevin, Gerrans, Emily, Pate, Louise, Anjum, Uruj, Coebergh, Jan, Eddy, Charlotte, Lahiri, Nayana, McEntagart, Meriel, Patton, Michael, Peterson, Maria, Rose, Sarah, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Chu, Elvina, Doherty, Karen, Haider, Salman, Hensman, Davina, Lewis, Monica, Novak, Marianne, Patel, Aakta, Robertson, Nicola, Rosser, Elisabeth, Tabrizi, Sarah, Taylor, Rachel, Warner, Thoma, Wild, Edward, Arran, Natalie, Bek, Judith, Callaghan, Jenny, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Krishnamoorthy, Ashok, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iri, Verstraelen, Nicola, Westmoreland, Leann, Cass, Ginette, Davidson, Lynn, Davison, Jill, Komati, Suresh, McDonnell, Sharon, Mohammed, Zeid, Morgan, Karen, Savage, Loi, Singh, Baldev, Wood, Josh, Knight, Caroline, O'Neill, Mari, Das Purkayastha, Debasish, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, Armstrong, Richard, Harrison, David, Hughes, Max, Large, Sandra, Donovan, John O, Palmer, Amy, Parkinson, Andrew, Soltysiak, Beverley, Timings, Leanne, Williams, Josh, Burn, John, Weekes, Rebecca, Craven, Janet, Bailey, Wendy, Coleman, Caroline, Haig-Brown, DIane, Simpson, Steve, Majeed, Tahir, Bandmann, Oliver, Bradbury, Alyson, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Gill, Paul, Kazoka, Mbombe, O'Donovan, Kirsty, Nevitt, Louise, Peppa, Nadia, Quarrell, Oliver, Taylor, Cat, Tidswell, Katherine, Agarwal, Veena, Anderson, Mary, Gunner, Kerry, Harris, Kayla, Hayward, Elaine, Heywood, Melanie, Keys, Liane, MacKinnon, Lesley, Kipps, Christopher, Smalley, Sarah, Bethwaite, Pamela, Edwards, Rachel, Fuller, Kathleen, Gowers, Lesley, Phillips, Michelle, Powell, Kingsley, Biunno, Ida, Bronzova, Juliana, Giuliano, Joe, Handley, Olivia J., Illarioshkin, Sergey, Illmann, Torsten, Levey, Jamie, McLean, Tim, Koivisto, Susana Pro, Päivärinta, Markku, Uhrova, Tereza, Betz, Sabrina, Come, Adrien, Capodarca, Selene, Charpentier, Sébastien, Da Silva, Wildson Vieira, DI Renzo, Martina, Finisterra, Ana Maria, Genoves, Camille, Gilling, Mette, Hvalstedt, Carina, Koppers, Kerstin, Lamanna, Claudia, Laurá, Matilde, Münkel, Kristina, Mütze, Lisanne, Oehmen, Martin, Padieu, Helene, Paterski, Laurent, Rindal, Beate, Røren, Niini, Šašinková, Pavla, Seliverstov, Yury, Timewell, Erika, Witjes-Ané, Marie-Noelle, Yudina, Elizaveta, Zielonka, Eugeniusz, Mcnulty, Paul, Hannequin, Didier, Diercks, Gabriele, Dressler, Dirk, Difruscolo, Olimpia, Van Hout, Monique S. E., Van Vugt, Jeroen P. P., Van Den Bogaard, Simon J. A., Hart'T, Ellen P., Roos, Raymund A. C., Dias, Margarida, Diéguez, Esther, Mcfadyen, Paula, Mcgill, Marie, Mckenzie, Sue, Dipple, Heather, Mcentagart, Meriel, Mcdonnell, Sharon, Haig-Brown, Diane, Mackinnon, Lesley, and Mclean, Tim
Subjects: Adult, Male, Adolescent, Huntington's disease, cancer, neurodegeneration, trinucleotide repeat, Cellular and Molecular Neuroscience, Young Adult, Neoplasms, Trinucleotide repeat, Humans, Genetic Predisposition to Disease, Prospective Studies, Registries, Age of Onset, Neurodegeneration, Child, Aged, Cancer, Aged, 80 and over, Huntingtin Protein, Incidence, Infant, Newborn, Infant, Middle Aged, Europe, Settore MED/26 - NEUROLOGIA, Huntington Disease, Huntington’s disease, Child, Preschool, Female, Neurology (clinical), Trinucleotide Repeat Expansion
Abstract: Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis.
Published: 2018
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45. Nigral and striatal connectivity alterations in asymptomaticLRRK2mutation carriers: A magnetic resonance imaging study

Author: M. Quintana, Eduardo Tolosa, Hugo C. Baggio, Yaroslau Compta, María José Martí, Carme Junqué, Miquel Aguilar, Barbara Segura, Francesc Valldeoriola, Jorge Hernández-Vara, Àngels Bayés, Matilde Calopa, Claustre Pont-Sunyer, and Dolores Vilas
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, medicine.diagnostic_test, Resting state fMRI, Precuneus, Parietal lobe, Magnetic resonance imaging, Biology, Asymptomatic, nervous system diseases, Cuneus, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Neurology, Mutation (genetic algorithm), medicine, Neurology (clinical), medicine.symptom, Asymptomatic carrier, Neuroscience, 030217 neurology & neurosurgery
Abstract: Background The study of functional connectivity by means of magnetic resonance imaging (MRI) in asymptomatic LRRK2 mutation carriers could contribute to the characterization of the prediagnostic phase of LRRK2-associated Parkinson's disease (PD). The objective of this study was to characterize MRI functional patterns during the resting state in asymptomatic LRRK2 mutation carriers. Methods We acquired structural and functional MRI data of 18 asymptomatic LRRK2 mutation carriers and 18 asymptomatic LRRK2 mutation noncarriers, all first-degree relatives of LRRK2-PD patients. Starting from resting-state data, we analyzed the functional connectivity of the striatocortical and the nigrocortical circuitry. Structural brain data were analyzed by voxel-based morphometry, cortical thickness, and volumetric measures. Results Asymptomatic LRRK2 mutation carriers had functional connectivity reductions between the caudal motor part of the left striatum and the ipsilateral precuneus and superior parietal lobe. Connectivity in these regions correlated with subcortical gray-matter volumes in mutation carriers. Asymptomatic carriers also showed increased connectivity between the right substantia nigra and bilateral occipital cortical regions (occipital pole and cuneus bilaterally and right lateral occipital cortex). No intergroup differences in structural MRI measures were found. In LRRK2 mutation carriers, age and functional connectivity correlated negatively with striatal volumes. Additional analyses including only subjects with the G2019S mutation revealed similar findings. Conclusions Asymptomatic LRRK2 mutation carriers showed functional connectivity changes in striatocortical and nigrocortical circuits compared with noncarriers. These findings support the concept that altered brain connectivity precedes the onset of classical motor features in a genetic form of PD. © 2016 International Parkinson and Movement Disorder Society
Published: 2016
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46. Relationship between quadriceps thickness measured by ultrasound and nutritional status at admission for hip fracture

Author: M. Gonzalez Fernandez, Miquel Aguilar, P. Huici Polo, Alejandro Sanz-Paris, A. Monge Vazquez, T. Sanclemente, Alejandro Sanz-Arque, N. Otero, V. Garcia Hoyos, L.E. Hueso Del Rio, and J.M. Arbones Mainar
Subjects: medicine.medical_specialty, Hip fracture, Nutrition and Dietetics, business.industry, Endocrinology, Diabetes and Metabolism, Ultrasound, Physical therapy, medicine, Nutritional status, medicine.disease, business
Published: 2020
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47. A comprehensive screening of copy number variability in dementia with Lewy bodies

Author: Sonja W. Scholz, Pentti J. Tienari, Dena G. Hernandez, Elisabet Londos, Alberto Lleó, Imelda Barber, Jose Bras, Owen A. Ross, Tanis J. Ferman, Tatiana Orme, Juan C. Troncoso, Andrew B. Singleton, John D. Eicher, John Hardy, Karen Marder, Tammaryn Lashley, Douglas Galasko, Liisa Myllykangas, Ted M. Dawson, Eliezer Masliah, David M. A. Mann, Ekaterina Rogaeva, Stuart Pickering-Brown, Monica Diez-Fairen, Claire Troakes, Peter St George-Hyslop, Nigel J. Cairns, Dennis W. Dickson, Lee Darwent, Thomas G. Beach, David J. Stone, Olga Pletnikova, Glenda M. Halliday, Jordi Clarimón, John Q. Trojanowski, Anne Braae, Claire E. Shepherd, Pau Pastor, Geidy E. Serrano, Susana Carmona, Minna Oinas, Andrew J. Lees, Afina W. Lemstra, Miquel Aguilar, Laura Parkkinen, Rita Guerreiro, Estrella Morenas-Rodríguez, Janice L. Holton, Olaf Ansorge, Tamas Revesz, Vivianna M. Van Deerlin, Neill R. Graff-Radford, Safa Al-Sarraj, Kristelle Brown, Valentina Escott-Price, Suzanne Lesage, Lawrence S. Honig, Celia Kun-Rodrigues, John C. Morris, Ronald C. Petersen, Henrik Zetterberg, Kevin Morgan, Brad F. Boeve, Lorraine N. Clark, Isabel Santana, Yaroslau Compta, Liana S. Rosenthal, Michael G. Heckman, Neurology, Amsterdam Neuroscience - Neurodegeneration, Department of Neurosciences, Research Programme for Molecular Neurology, Pentti Tienari / Principal Investigator, Neurologian yksikkö, Research Programs Unit, Clinicum, Department of Pathology, Liisa Tellervo Myllykangas / Principal Investigator, Medicum, Neurokirurgian yksikkö, and HUS Neurocenter
Subjects: 0301 basic medicine, Male, Aging, Candidate gene, ALPHA-SYNUCLEIN, Dementia with Lewy bodies, Genome-wide association study, Variações do Número de Cópias de DNA, 3124 Neurology and psychiatry, 0302 clinical medicine, RARE, genetics [Lewy Body Disease], genetics [Adaptor Proteins, Signal Transducing], PURINE METABOLISM, MAPT GENE, MAPT, GLUCOCEREBROSIDASE MUTATIONS, Genome-wide, Copy-number variation, genetics [Genetic Predisposition to Disease], SNAPSHOT GENETICS, SYNUCLEIN GENE DUPLICATION, Aged, 80 and over, Oncogene Proteins, Genome, General Neuroscience, 3. Good health, ALZHEIMERS-DISEASE, genetics [Membrane Proteins], genetics [Polymorphism, Single Nucleotide], Medical genetics, Female, Lewy Body Disease, medicine.medical_specialty, Doença por Corpos de Lewy, DNA Copy Number Variations, genetics [DNA Copy Number Variations], Computational biology, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 03 medical and health sciences, mental disorders, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genetic variability, GENOME-WIDE ASSOCIATION, Genotyping, PARKINSON-DISEASE, Genetic association, Adaptor Proteins, Signal Transducing, Copy number variants, Membrane Proteins, genetics [Oncogene Proteins], medicine.disease, nervous system diseases, Proteínas Oncogénicas, 030104 developmental biology, SNCA, Neurology (clinical), Geriatrics and Gerontology, Predisposição Genética para Doença, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study
Abstract: The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk. (C) 2019 Elsevier Inc. All rights reserved.
Published: 2019
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48. Cerebrospinal fluid cytokines in multiple system atrophy: A cross-sectional Catalan MSA registry study

Author: Matilde Calopa, Lluís Planellas, Ana Cámara, Esteban Muñoz, Darly M. Giraldo, Serge Jauma Classen, Asunción Ávila, Jorge Hernández-Vara, Rubén Fernández-Santiago, Francesc Valldeoriola, Paloma Bravo, Montserrat Pujol, Carles Gaig, J. Pagonabarraga, Mario Ezquerra, Teresa Botta, Neus Fabregat, Sara P. Dias, Miquel Aguilar, José Ríos, Manel Fernández, Marta Pulido-Salgado, Eduardo Tolosa, Àngels Bayés, Oriol De Fabregues, Gian Gaetano Tartaglia, Pau Pastor, Claustre Pont, Víctor Puente, Yaroslau Compta, Almudena Sánchez, Josep Saura, Jaume Campdelacreu, Celia Painous, Nuria Caballol, María José Martí, Alexandra Pérez-Soriano, and Graduate School
Subjects: 0301 basic medicine, Eotaxin, Male, medicine.medical_specialty, Parkinson's disease, medicine.medical_treatment, Pilot Projects, Logistic regression, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Atrophy, CHLC NEU, Internal medicine, medicine, Humans, Registries, Aged, Inflammation, medicine.diagnostic_test, Receiver operating characteristic, Lumbar puncture, business.industry, Multiple system atrophy, Multiple System Atrophy, Middle Aged, medicine.disease, Biomarkers, Cytokines, Cross-Sectional Studies, Female, Spain, 030104 developmental biology, Cytokine, Neurology, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery
Abstract: Introduction: Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis. Methods: Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture. Results: There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores. Conclusion: Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA. info:eu-repo/semantics/publishedVersion
Published: 2019

49. Heritability and genetic variance of dementia with Lewy bodies

Author: Rita Guerreiro, Jose Bras, Tanis J. Ferman, Stuart Pickering-Brown, Susana Carmona, Laura Parkkinen, Andrew B. Singleton, Glenda M. Halliday, Jordi Clarimón, Lee Darwent, Olaf Ansorge, Monica Diez-Fairen, Karen Marder, Geidy E. Serrano, David M. A. Mann, Thomas G. Beach, Michael G. Heckman, Andrew J. Lees, Miquel Aguilar, Liisa Myllykangas, Tatiana Orme, Henrik Zetterberg, Alberto Lleó, Lorraine N. Clark, Estrella Morenas-Rodriguez, Claire E. Shepherd, Ekaterina Rogaeva, Elisabet Londos, Douglas Galasko, Isabel Santana, Nadia Dehghani, Kevin Morgan, Eliezer Masliah, Imelda Barber, John D. Eicher, Ronald C. Petersen, Brad F. Boeve, John Hardy, Claire Troakes, Joao Luis Neto, Celia Kun-Rodrigues, Peter St George-Hyslop, Dennis W. Dickson, Janice L. Holton, Pentti J. Tienari, Minna Oinas, Olga Pletnikova, Afina W. Lemstra, John Q. Trojanowski, John C. Morris, Liana S. Rosenthal, Anne Braae, Dena G. Hernandez, Nigel J. Cairns, Pau Pastor, David J. Stone, Juan C. Troncoso, Ted M. Dawson, Owen A. Ross, Tammaryn Lashley, Tamas Revesz, Yaroslau Compta, Sonja W. Scholz, Neill R. Graff-Radford, Safa Al-Sarraj, Vivianna M. Van Deerlin, Kristelle Brown, Valentina Escott-Price, Suzanne Lesage, Lawrence S. Honig, HUS Neurocenter, Department of Neurosciences, Neurologian yksikkö, Research Programs Unit, STEMM - Stem Cells and Metabolism Research Program, Department of Pathology, Helsinki University Hospital Area, Neurokirurgian yksikkö, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Lewy Body Disease, 0301 basic medicine, Genetic correlation, Linkage disequilibrium, LOCI, Genome-wide association study, Biology, Article, 3124 Neurology and psychiatry, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, genetics [Lewy Body Disease], Missing heritability problem, MISSING HERITABILITY, ddc:570, Databases, Genetic, Genetic variation, mental disorders, medicine, Humans, Genetic Predisposition to Disease, POLYGENIC RISK, Genetic variability, GENOME-WIDE ASSOCIATION, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Genetic variance, METAANALYSIS, 030304 developmental biology, Genetics, ARCHITECTURE, 0303 health sciences, Dementia with Lewy bodies, 3112 Neurosciences, Genetic Variation, Heritability, Explained variation, medicine.disease, 3. Good health, ALZHEIMERS-DISEASE, 030104 developmental biology, Neurology, Dementia, Lewy bodies, 030217 neurology & neurosurgery
Abstract: Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson’s disease (PD) or Alzheimer’s disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.
Published: 2018
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50. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

Author: Ellen Gelpi, Mathieu Vandenbulcke, Yalda Baradaran-Heravi, Alex Michotte, Alexandre de Mendonça, Elisa Bonomi, Peter Paul De Deyn, Peter Heutink, Bruno Bergmans, Matthew J. Fraidakis, Matthis Synofzik, Dirk Peeters, Eva Parobkova, Christine Van Broeckhoven, Patrick Santens, Peter De Jonghe, Radoslav Matej, Maria Rosário Almeida, Rik Vandenberghe, Hung Phuoc Nguyen, Pau Pastor, Alessandro Padovani, Gabriel Miltenberger-Miltenyi, Jan De Bleecker, Philip Van Damme, Sara Van Mossevelde, Isabel Santana, Ricard Rojas-García, Olivier Deryck, Julie van der Zee, Eric Salmon, Ana Verdelho, Christiana Willems, Nina De Klippel, Miquel Aguilar, Lubina Dillen, Alberto Lleó, Sergi Borrego-Écija, Sebastiaan Engelborghs, Sandro Sorbi, Jonathan Baets, Camilla Ferrari, Monica Diez-Fairen, Silvia Bagnoli, Barbara Borroni, Raquel Sánchez-Valle, Johan Goeman, Anne Sieben, Ignacio Illán-Gala, Patrick Cras, Panagiotis Alexopoulos, Janina Turon-Sans, Benedetta Nacmias, Adrian Ivanoiu, Irene Piaceri, Janine Diehl-Schmid, Jan Versijpt, Silvana Archettim, C. Ferreira, Frederico Simões do Couto, Jordi Clarimón, Dirk Nuytten, Javier Simón-Sánchez, Carlo Wilke, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, BELNEU Consortium1, EU EOD Consortium, Clinical sciences, Neurology, and Pathologic Biochemistry and Physiology
Subjects: 0301 basic medicine, Oncology, Male, Aging, Geriatrics & Gerontology, Gene mutation, Frontotemporal dementia (FTD), AMYOTROPHIC-LATERAL-SCLEROSIS, Pathogenesis, Cohort Studies, 0302 clinical medicine, Gene Frequency, Medicine and Health Sciences, Missense mutation, Amyotrophic lateral sclerosis (ALS), Amyotrophic lateral sclerosis, genetics [Frontotemporal Dementia], Medicine(all), General Neuroscience, ddc, genetics [Amyotrophic Lateral Sclerosis], genetics [European Continental Ancestry Group], Frontotemporal Dementia, Cohort, T cellerestricted intracellular antigen-1 gene (TIA1), Female, Life Sciences & Biomedicine, Cohort study, Frontotemporal dementia, medicine.medical_specialty, European Continental Ancestry Group, genetics [White People], Mutation, Missense, White People, 03 medical and health sciences, Internal medicine, mental disorders, medicine, Humans, ddc:610, genetics [T-Cell Intracellular Antigen-1], Biology, Allele frequency, T cell–restricted intracellular antigen-1 gene (TIA1), Science & Technology, business.industry, TIA1 protein, human, Amyotrophic Lateral Sclerosis, Neurosciences, TAR DNA-Binding protein 43 (TDP-43), FRONTOTEMPORAL DEMENTIA, medicine.disease, T-Cell Intracellular Antigen-1, 030104 developmental biology, Human medicine, Neurology (clinical), Neurosciences & Neurology, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract: We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated. ispartof: NEUROBIOLOGY OF AGING vol:69 ispartof: location:United States status: published
Published: 2018
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