23 results on '"Isabel Sala"'
Search Results
2. Genome-wide association study of Alzheimer's disease CSF biomarkers in the EMIF-AD Multimodal Biomarker Discovery dataset
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Pablo Martinez-Lage, Ulf Andreasson, Richard Dobson, Ellis Niemantsverdriet, Fabian Kilpert, Mikel Tainta, Michael Wittig, Mara ten Kate, Simon Lovestone, Lars Bertram, Henrik Zetterberg, Stephanie J.B. Vos, Dmitry Prokopenko, Frederik Barkhof, Jolien Schaeverbeke, Philip Scheltens, Shengjun Hong, Jill C. Richardson, Olivier Blin, Valerija Dobricic, Pieter Jelle Visser, Silvy Gabel, Cristina Legido-Quigley, Giovanni B. Frisoni, Johannes Streffer, Isabel Sala, Sebastiaan Engelborghs, José Luis Molinuevo, Andre Franke, Alberto Lleó, Isabelle Bos, Rudolph E. Tanzi, Lorena Rami, Kristel Sleegers, Betty M. Tijms, Régis Bordet, Charlotte E. Teunissen, Petronella Kettunen, Rik Vandenberghe, Julius Popp, Isabelle Cleynen, Gwendoline Peyratout, Kaj Blennow, Anders Wallin, Christine Van Broeckhoven, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Alzheimers Dis Neuroimaging Initia, Universität zu Lübeck = University of Lübeck [Lübeck], Massachusetts General Hospital [Boston], Maastricht University [Maastricht], Vrije Universiteit Amsterdam [Amsterdam] (VU), University of Gothenburg (GU), Sahlgrenska University Hospital [Gothenburg], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Université de Genève = University of Geneva (UNIGE), Istituto Centro San Giovanni di Dio Fatebenefratelli, Partenaires INRAE, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), CHU Lille, Université de Lille, Clinic Barcelona Hospital Universitari, University of Oxford, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Geneva University Hospital (HUG), Lausanne University Hospital, Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián], King‘s College London, University College of London [London] (UCL), Steno Diabetes Center, VIB [Belgium], Amsterdam UMC - Amsterdam University Medical Center, UCL Institute of Neurology, Queen Square [London], UK Dementia Research Institute (UK DRI), UCB BioPharma [Braine l’Alleud, Belgium], Christian-Albrechts University of Kiel, University of Oslo (UiO), Alzheimer's Disease Neuroimaging Initiative (ADNI), Amsterdam Neuroscience - Neurodegeneration, Neurology, Laboratory Medicine, Radiology and nuclear medicine, Clinical sciences, Neuroprotection & Neuromodulation, and Pathologic Biochemistry and Physiology
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0301 basic medicine ,Male ,Genome-wide association study ,0302 clinical medicine ,RISK VARIANTS ,Biomarker discovery ,MIF-AD Multimodal Biomarker Discovery dataset ,Psychiatry ,Alzheimer's disease ,Psychiatry and Mental health ,Female ,Life Sciences & Biomedicine ,SUSCEPTIBILITY LOCI ,Neuroscience(all) ,Single-nucleotide polymorphism ,Genomics ,tau Proteins ,Computational biology ,Biology ,Molecular neuroscience ,elderly ,Article ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,medicine ,Dementia ,SNP ,Humans ,CSF biomarkers ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,Aged ,Amyloid beta-Peptides ,Science & Technology ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,Neurodegenerative disorder ,medicine.disease ,Personalized medicine ,Genetic architecture ,Peptide Fragments ,030104 developmental biology ,Human medicine ,TAU ,business ,030217 neurology & neurosurgery ,Biomarkers ,dementia ,Genome-Wide Association Study - Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the most common form of dementia in the elderly. Susceptibility to AD is considerably determined by genetic factors which hitherto were primarily identified using case–control designs. Elucidating the genetic architecture of additional AD-related phenotypic traits, ideally those linked to the underlying disease process, holds great promise in gaining deeper insights into the genetic basis of AD and in developing better clinical prediction models. To this end, we generated genome-wide single-nucleotide polymorphism (SNP) genotyping data in 931 participants of the European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) sample to search for novel genetic determinants of AD biomarker variability. Specifically, we performed genome-wide association study (GWAS) analyses on 16 traits, including 14 measures derived from quantifications of five separate amyloid-beta (Aβ) and tau-protein species in the cerebrospinal fluid (CSF). In addition to confirming the well-established effects of apolipoprotein E (APOE) on diagnostic outcome and phenotypes related to Aβ42, we detected novel potential signals in the zinc finger homeobox 3 (ZFHX3) for CSF-Aβ38 and CSF-Aβ40 levels, and confirmed the previously described sex-specific association between SNPs in geminin coiled-coil domain containing (GMNC) and CSF-tau. Utilizing the results from independent case–control AD GWAS to construct polygenic risk scores (PRS) revealed that AD risk variants only explain a small fraction of CSF biomarker variability. In conclusion, our study represents a detailed first account of GWAS analyses on CSF-Aβ and -tau-related traits in the EMIF-AD MBD dataset. In subsequent work, we will utilize the genomics data generated here in GWAS of other AD-relevant clinical outcomes ascertained in this unique dataset.
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- 2020
3. Characteristics and prognosis of patients with mild cognitive impairment by cerebrospinal fluid biomarker profiles
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Estrella Morenas-Rodríguez, Maria Belén Sánchez-Saudinós, Ignacio Illán-Gala, Maria Carmona-Iragui, Juan Fortea, Tomás Xucla, Isabel Barroeta, Miguel A Santos-Santos, Daniel Alcolea, Alberto Lleó, Isabel Sala, Teresa Estellés, Miren Altuna, and Rafael Blesa
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Oncology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Cerebrospinal fluid ,Developmental Neuroscience ,Internal medicine ,medicine ,Biomarker (medicine) ,Neurology (clinical) ,Geriatrics and Gerontology ,Cognitive impairment ,business - Published
- 2020
4. Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort
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Isabelle Bos, Gwendoline Peyratout, Yvonne Freund-Levi, Ellen Elisa De Roeck, Mara ten Kate, Kristel Sleegers, Susan Baker, Mikel Tainta, Lutz Frölich, Giovanni B. Frisoni, Cristina Legido-Quigley, Karen Meersmans, Andrey Kormilitzin, Abdul Hye, Valerija Dobricic, Alison L. Baird, Alberto Lleó, Régis Bordet, Johannes Streffer, Isabel Sala, Sneha N Anand, Lorena Rami, B. Paul Morgan, Silvy Gabel, Julius Popp, Noel J. Buckley, Olivier Blin, José Luis Molinuevo, Sarah Westwood, Angharad R. Morgan, Frans R.J. Verhey, Pieter Jelle Visser, Magda Tsolaki, Martinez-Lage P, Rik Vandenberghe, Alejo J. Nevado-Holgado, Simon Lovestone, Lars Bertram, Henrik Zetterberg, Anders Wallin, Philip Scheltens, Peter Johannsen, Nicholas J. Ashton, Charlotte E. Teunissen, Petronella Kettunen, Sebastiaan Engelborghs, Stephanie J.B. Vos, Frederik Barkhof, Liu Shi, Jill C. Richardson, University of Oxford, King‘s College London, University of Gothenburg (GU), Cardiff University, Maastricht University [Maastricht], Janssen Research & Development, VU University Medical Center [Amsterdam], University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Université de Genève = University of Geneva (UNIGE), Istituto Centro San Giovanni di Dio Fatebenefratelli, Partenaires INRAE, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Université de Lille, CHU Lille, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Universitat Pompeu Fabra [Barcelona] (UPF), Sahlgrenska Academy at University of Gothenburg [Göteborg], AHEPA University General Hospital [Thessaloniki], Hospital de la Santa Creu i Sant Pau, Lausanne University Hospital, Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián], Copenhagen University Hospital, Karolinska University Hospital [Stockholm], Universität Heidelberg [Heidelberg] = Heidelberg University, Universität zu Lübeck = University of Lübeck [Lübeck], Steno Diabetes Center, University of Oslo (UiO), Institutes of Neurology and Healthcare Engineering, UCL, London, Sahlgrenska University Hospital [Gothenburg], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), UCL, Institute of Neurology [London], UCB Pharma S.A.[Braine-l'Alleud], UCB Pharma [Brussels], Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), Faculty of Arts and Philosophy, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Educational Science, Rissman, R, Radiology and nuclear medicine, and Amsterdam Neuroscience - Neurodegeneration
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0301 basic medicine ,Apolipoprotein E ,Oncology ,Male ,MILD COGNITIVE IMPAIRMENT ,Alzheimer’s disease ,amyloid-β ,biomarkers ,plasma ,proteomics ,Apolipoprotein E4 ,PROGRESSION ,Disease ,Proteomics ,GUIDELINES ,Cohort Studies ,ddc:616.89 ,0302 clinical medicine ,MARKERS ,BLOOD-BASED BIOMARKER ,Biomarker discovery ,Medicine(all) ,biology ,General Neuroscience ,DEMENTIA ,General Medicine ,Blood Proteins ,Middle Aged ,CEREBROSPINAL-FLUID BIOMARKERS ,Alzheimer's disease ,Blood proteins ,Magnetic Resonance Imaging ,amyloid-beta ,3. Good health ,Psychiatry and Mental health ,Clinical Psychology ,Body Burden ,Female ,Sample collection ,Life Sciences & Biomedicine ,Research Article ,EXPRESSION ,medicine.medical_specialty ,Amyloid beta ,tau Proteins ,03 medical and health sciences ,Alzheimer Disease ,Internal medicine ,medicine ,Dementia ,Humans ,Amyloid-β ,Cognitive Dysfunction ,Biology ,Aged ,Science & Technology ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,Neurosciences ,LECTIN ,medicine.disease ,Cerebral Amyloid Angiopathy ,PATHOLOGY ,030104 developmental biology ,ROC Curve ,Positron-Emission Tomography ,biology.protein ,Neurosciences & Neurology ,Human medicine ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure. ispartof: JOURNAL OF ALZHEIMERS DISEASE vol:74 issue:1 pages:213-225 ispartof: location:Netherlands status: published
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- 2020
5. Clinical Subtypes of Dementia with Lewy Bodies Based on the Initial Clinical Presentation
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Andrea Subirana, Maria Carmona-Iragui, Ignacio Illán-Gala, Ma Belén Sánchez-Saudinós, Elba Pascual-Goñi, Roser Ribosa-Nogué, Juan Fortea, Valle Camacho, Estrella Morenas-Rodríguez, Isabel Sala, Rafael Blesa, Alberto Lleó, and Daniel Alcolea
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Lewy Body Disease ,Male ,0301 basic medicine ,medicine.medical_specialty ,Hallucinations ,Disease ,Neuropsychological Tests ,03 medical and health sciences ,0302 clinical medicine ,Parkinsonian Disorders ,Rating scale ,Internal medicine ,medicine ,Cluster Analysis ,Humans ,Dementia ,Age of Onset ,Aged ,Retrospective Studies ,Aged, 80 and over ,Psychiatric Status Rating Scales ,Dementia with Lewy bodies ,business.industry ,General Neuroscience ,Parkinsonism ,Medical record ,Neuropsychology ,General Medicine ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,030104 developmental biology ,Disease Progression ,Female ,Geriatrics and Gerontology ,Presentation (obstetrics) ,Cognition Disorders ,business ,030217 neurology & neurosurgery - Abstract
BACKGROUND Dementia with Lewy bodies (DLB) is a heterogeneous disease in which clinical presentation, symptoms, and evolution widely varies between patients. OBJECTIVE To investigate the existence of clinical subtypes in DLB based on the initial clinical presentation. METHODS 81 patients with a clinical diagnosis of probable DLB were consecutively included. All patients underwent a neurological evaluation including a structured questionnaire about neuropsychiatric symptoms and sleep, an assessment of motor impairment (Unified Parkinson Disease Rating Scale subscale III), and a formal neuropsychological evaluation. Onset of core symptoms (hallucinations, parkinsonism, and fluctuations) and dementia were systematically reviewed from medical records. We applied a K-means clustering method based on the initial clinical presentation. RESULTS Cluster analysis yielded three different groups. Patients in cluster I (cognitive-predominant, n = 46) presented more frequently with cognitive symptoms (95.7%, n = 44, p < 0.001), and showed a longer duration from onset to DLB diagnosis (p < 0.001) than the other clusters. Patients in cluster II (neuropsychiatric-predominant, n = 22) were older at disease onset (78.1±5 versus 73.6±6.1 and 73.6±4.2 in clusters I and III, respectively, both p < 0.01), presented more frequently with psychotic symptoms (77.3%, n = 17), and had a shorter duration until the onset of hallucinations (p < 0.001). Patients in cluster III (parkinsonism-predominant, n = 13) showed a shorter time from onset to presence of parkinsonism (p < 0.001) and dementia (0.008). CONCLUSIONS Three clinical subtypes of DLB can be defined when considering the differential initial presentations. The proposed subtypes have distinct clinical profiles and progression patterns.
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- 2018
6. Diagnostic and Prognostic Value of the Combination of Two Measures of Verbal Memory in Mild Cognitive Impairment due to Alzheimer’s Disease
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Jordi Clarimón, Andrea Subirana, Isabel Sala, Juan Fortea, Maria Carmona-Iragui, Alberto Lleó, Laura Videla, Sergio Andrés Salgado, Ignacio Illán-Gala, Daniel Alcolea, Rafael Blesa, Estrella Morenas-Rodríguez, Ma Belén Sánchez-Saudinós, and Roser Ribosa-Nogué
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Male ,0301 basic medicine ,medicine.medical_specialty ,tau Proteins ,Neuropsychological Tests ,Logistic regression ,03 medical and health sciences ,Apolipoproteins E ,0302 clinical medicine ,Alzheimer Disease ,Memory ,Internal medicine ,mental disorders ,medicine ,Humans ,Dementia ,Cognitive Dysfunction ,Memory disorder ,Longitudinal Studies ,Prospective Studies ,Prospective cohort study ,Episodic memory ,Aged ,Proportional Hazards Models ,Amyloid beta-Peptides ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,General Neuroscience ,General Medicine ,Neuropsychological test ,Prognosis ,medicine.disease ,Peptide Fragments ,Psychiatry and Mental health ,Clinical Psychology ,Logistic Models ,030104 developmental biology ,Disease Progression ,Speech Perception ,Female ,Geriatrics and Gerontology ,Verbal memory ,business ,Biomarkers ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Background Episodic memory impairment is the core feature of typical Alzheimer's disease. Objective To evaluate the performance of two commonly used verbal memory tests to detect mild cognitive impairment due to Alzheimer's disease (MCI-AD) and to predict progression to Alzheimer's disease dementia (AD-d). Methods Prospective study of MCI patients in a tertiary memory disorder unit. Patients underwent an extensive neuropsychological battery including two tests of declarative verbal memory: The Free and Cued Selective Reminding Test (FCSRT) and the word list learning task from the Consortium to Establish a Registry for Alzheimer's disease (CERAD-WL). Cerebrospinal fluid (CSF) was obtained from all patients and MCI-AD was defined by means of the t-Tau/Aβ1-42 ratio. Logistic regression analyses tested whether the combination of FCSRT and CERAD-WL measures significantly improved the prediction of MCI-AD. Progression to AD-d was analyzed in a Cox regression model. Results A total of 202 MCI patients with a mean follow-up of 34.2±24.2 months were included and 98 (48.5%) met the criteria for MCI-AD. The combination of FCSRT and CERAD-WL measures improved MCI-AD classification accuracy based on CSF biomarkers. Both tests yielded similar global predictive values (59.9-65.3% and 59.4-62.8% for FCSRT and CERAD-WL, respectively). MCI-AD patients with deficits in both FCSRT and CERAD-WL had a faster progression to AD-d than patients with deficits in only one test. Conclusions The combination of FCSRT and CERAD-WL improves the classification of MCI-AD and defines different prognostic profiles. These findings have important implications for clinical practice and the design of clinical trials.
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- 2017
7. Cerebral amyloid angiopathy in Down syndrome and sporadic and autosomal‐dominant Alzheimer's disease
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Albert Lladó, Sofía González-Ortiz, Michael S. Rafii, Susana Fernández, Juan Fortea, Maria Belén Sánchez-Saudinós, Sebastián Videla, Roser Ribosa-Nogué, Jordi Clarimón, Mircea Balasa, Raquel Sánchez-Valle, Maria Carmona-Iragui, Elizabeth Head, Ignacio Illán-Gala, José Luis Molinuevo, Daniel Alcolea, Alberto Lleó, Isabel Sala, Frederick A. Schmitt, Estrella Morenas-Rodríguez, David K. Powell, Bessy Benejam, Rafael Blesa, Beatriz Bosch, and Laura Videla
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Adult ,Male ,0301 basic medicine ,Apolipoprotein E ,Pathology ,medicine.medical_specialty ,Down syndrome ,Apolipoprotein B ,Epidemiology ,Apolipoprotein E4 ,Disease ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cerebrospinal fluid ,Gene Frequency ,Developmental Neuroscience ,Alzheimer Disease ,mental disorders ,Genotype ,medicine ,Humans ,cardiovascular diseases ,Aged ,Amyloid beta-Peptides ,biology ,Health Policy ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Peptide Fragments ,Cerebral Amyloid Angiopathy ,Psychiatry and Mental health ,030104 developmental biology ,biology.protein ,Biomarker (medicine) ,Female ,Neurology (clinical) ,Cerebral amyloid angiopathy ,Down Syndrome ,Geriatrics and Gerontology ,Psychology ,030217 neurology & neurosurgery - Abstract
Introduction We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]). Methods Neuroimaging features of CAA, apolipoprotein ( APOE ), and cerebrospinal fluid amyloid β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD ( n = 42), and healthy controls ( n = 68). Results CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE e4 genotype was borderline significantly associated with CAA in sporadic EOAD ( P = .06) but not with DS or ADAD. There were no differences in Aβ040 levels between groups or between subjects with and without CAA. Discussion CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Aβ40 levels are not a useful biomarker for CAA in AD.
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- 2017
8. Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort
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Lutz Frölich, Kaj Blennow, Karen Meersmans, Kristel Sleegers, Cristina Legido-Quigley, Mara ten Kate, Tommi Suvitaival, Julius Popp, Frederik Barkhof, Sarah Westwood, Tahmina Ahmad, Petra Proitsi, Jill C. Richardson, Magda Tsolaki, José Luis Molinuevo, Mikel Tainta, Alison L. Baird, Pablo Martinez-Lage, Philip Scheltens, Abdul Hye, Yvonne Freund-Levi, Lorena Rami, Adnan Ali, Stephanie J.B. Vos, Frans R.J. Verhey, Stuart G. Snowden, Rik Vandenberghe, Valerija Dobricic, Charlotte E. Teunissen, Pieter Jelle Visser, Petronella Kettunen, Min Kim, Peter Johannsen, Régis Bordet, David J. Merkler, Nicholas J. Ashton, Alberto Lleó, Henrik Zetterberg, Gwendoline Peyratout, Alejo J. Nevado-Holgado, Anders Wallin, Sebastiaan Engelborghs, Olivier Blin, Johannes Streffer, Isabel Sala, Isabelle Bos, Simon Lovestone, Ellen De Roeck, Lars Bertram, Silvy Gabel, Giovanni B. Frisoni, King‘s College London, University of Cambridge [UK] (CAM), Steno Diabetes Center of Copenhagen [Gentofte, Denmark], University of South Florida [Tampa] (USF), University of Oxford, Maastricht University [Maastricht], University Hospitals Leuven [Leuven], Amsterdam UMC - Amsterdam University Medical Center, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM), GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), University of Antwerp (UA), Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, CHU Lille, Hospital Clinic (IDIBAPS), University of Gothenburg (GU), AHEPA University General Hospital [Thessaloniki], Hospital de la Santa Creu i Sant Pau, Lausanne University Hospital, Center for Research and Advanced Therapies CITA-Alzheimer Foundation [San Sebastián], Copenhagen University Hospital, Karolinska University Hospital [Stockholm], Universität Heidelberg [Heidelberg] = Heidelberg University, Universität zu Lübeck = University of Lübeck [Lübeck], Université de Genève = University of Geneva (UNIGE), Geneva University Hospital (HUG), Sahlgrenska University Hospital [Gothenburg], UCL, Institute of Neurology [London], Janssen Pharmaceutica [Beerse], Universität Heidelberg [Heidelberg], Otten, Lisa, Clinical sciences, Neurology, Amsterdam Neuroscience - Neurodegeneration, Laboratory Medicine, Radiology and nuclear medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and MUMC+: MA Med Staf Spec Psychiatrie (9)
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0301 basic medicine ,Oncology ,Male ,Neurology ,Epidemiology ,Neuropsychological Tests ,Hippocampus ,RECOMMENDATIONS ,Cohort Studies ,ddc:616.89 ,0302 clinical medicine ,Cerebrospinal fluid ,MARKERS ,Biomarker discovery ,Brain volume measurements ,Medicine(all) ,OLEAMIDE ,biology ,medicine.diagnostic_test ,Health Policy ,Brain ,INDUCED LIPOKINE ,EMIF-AD ,Amyloidosis ,Middle Aged ,Alzheimer's disease ,Magnetic Resonance Imaging ,PERTURBATIONS ,3. Good health ,Psychiatry and Mental health ,ACID ,Female ,Alzheimer’s disease ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Amyloid ,Tau protein ,Clinical Neurology ,tau Proteins ,CSF ,METABOLISM ,Article ,Aged ,Amyloid beta-Peptides/blood ,Amyloid beta-Peptides/cerebrospinal fluid ,Amyloidosis/blood ,Amyloidosis/cerebrospinal fluid ,Amyloidosis/metabolism ,Biomarkers/blood ,Biomarkers/cerebrospinal fluid ,Brain/pathology ,Cognitive Dysfunction/diagnosis ,Hippocampus/metabolism ,Humans ,Memory/physiology ,Metabolomics ,tau Proteins/blood ,tau Proteins/cerebrospinal fluid ,Biomarkers ,Cognitive function measurements ,Dementia ,Tau ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Memory ,Internal medicine ,12,13-DIHOME ,medicine ,13-DIHOME ,Cognitive Dysfunction ,BIOSYNTHESIS ,Biology ,Mini–Mental State Examination ,Amyloid beta-Peptides ,Science & Technology ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,medicine.disease ,030104 developmental biology ,ddc:618.97 ,biology.protein ,Human medicine ,Neurology (clinical) ,Neurosciences & Neurology ,Geriatrics and Gerontology ,business ,030217 neurology & neurosurgery - Abstract
Introduction: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.Methods: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.Results: Eight metabolites were associated with amyloid b and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.Discussion: PFAMs have been found increased and associated with amyloid b burden in CSF and clinical measures. Crown Copyright (C) 2019 Published by Elsevier Inc. on behalf of the Alzheimer's Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
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- 2019
9. Progranulin Protein Levels in Cerebrospinal Fluid in Primary Neurodegenerative Dementias
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Maria Carmona-Iragui, Jordi Clarimón, Alberto Lleó, Laura Cervera-Carles, Estrella Morenas-Rodríguez, Eduard Vilaplana, Isabel Sala, Roser Ribosa-Nogué, Rafael Blesa, M. Belen Sánchez-Saudinós, Oriol Dols-Icardo, Laia Muñoz-Llahuna, Daniel Alcolea, and Juan Fortea
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Male ,medicine.medical_specialty ,tau Proteins ,Disease ,Polymorphism, Single Nucleotide ,cerebrospinal fluid ,Progressive supranuclear palsy ,Progranulins ,Cerebrospinal fluid ,Polymorphism (computer science) ,Internal medicine ,mental disorders ,progranulin ,medicine ,Humans ,Dementia ,tau ,plasma ,Aged ,Aged, 80 and over ,Amyloid beta-Peptides ,business.industry ,Dementia with Lewy bodies ,General Neuroscience ,Neurodegenerative Diseases ,General Medicine ,Alzheimer's disease ,Middle Aged ,medicine.disease ,amyloid-beta ,Psychiatry and Mental health ,Clinical Psychology ,Endocrinology ,biomarker ,Intercellular Signaling Peptides and Proteins ,Biomarker (medicine) ,Female ,Geriatrics and Gerontology ,business ,Biomarkers ,dementia ,Frontotemporal dementia - Abstract
Background: Progranulin is implicated in frontotemporal dementia (FTD), but its role in other neurodegenerative disorders is unknown. Objective: To investigate the levels of progranulin (PGRN) in cerebrospinal fluid (CSF) in different neurodegenerative dementias and their correlation with levels in plasma in cognitively normal subjects. Methods: We measured PGRN in CSF in 229 patients with amnestic mild cognitive impairment, Alzheimer's disease dementia, sporadic FTD, dementia with Lewy bodies, corticobasal syndrome, or progressive supranuclear palsy. We also measured PGRN in CSF and plasma in 74 cognitively normal individuals. We examined the correlation between PGRN levels in CSF and diagnosis, cortical thickness, genetic factors and other CSF biomarkers. We also investigated the correlation between plasma and CSF levels of PGRN in cognitively normal individuals. Results: CSF levels did not differ across diagnoses or correlate with cortical thickness. Polymorphism rs5848 in GRN influenced CSF PGRN levels, but APOE epsilon 4 allele did not. Amyloid-beta(42), t-tau, p-tau, and YKL-40 levels correlated weakly with PGRN in CSF. We found a weak correlation (r = 0.362) between plasma and CSF PGRN levels in cognitively normal individuals. Conclusions: Our findings do not support a diagnostic value of CSF PGRN in neurodegenerative diseases. Our data confirm that levels of PGRN in plasma do not reflect accurately levels in CSF in cognitively normal controls. These data should be considered in clinical trials aiming to increase PGRN.
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- 2016
10. Copy number variation analysis of the 17q21.31 region and its role in neurodegenerative diseases
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Isabel Sala, Antonia Campolongo, Pau Pastor, Daniel Alcolea, Laura Cervera-Carles, Rafael Blesa, A. Lleo, Jaime Kulisevsky, Estrella Morenas-Rodriguez, Juan Fortea, J. Pagonabarraga, Berta Pascual-Sedano, and Jordi Clarimón
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Male ,0301 basic medicine ,Parkinson's disease ,DNA Copy Number Variations ,Biology ,Bioinformatics ,Progressive supranuclear palsy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Gene Frequency ,medicine ,Humans ,Corticobasal degeneration ,Copy-number variation ,Allele ,Genetics (clinical) ,Aged ,Demography ,Segmental duplication ,Genetics ,Dementia with Lewy bodies ,Haplotype ,Neurodegenerative Diseases ,medicine.disease ,Psychiatry and Mental health ,030104 developmental biology ,Case-Control Studies ,Female ,030217 neurology & neurosurgery ,Chromosomes, Human, Pair 17 - Abstract
The H1 haplotype of the 17q21.31 inversion polymorphism has been consistently associated with progressive supranuclear palsy, corticobasal degeneration, and Parkinson's disease in Caucasians. Recently, large polymorphic segmental duplications resulting into complex rearrangements at this locus with a high diversity range in human populations have been revealed. We sought to explore whether the two multi-allelic copy number variants that are present in the H1 clade (with segmental duplications of 300 and 218 kilobases in length) could be responsible for the known H1-related risk of developing these neurodegenerative disorders. A total of 857 Spanish subjects including 330 patients with Parkinson's disease, 96 with progressive supranuclear palsy, 55 with corticobasal degeneration, 51 dementia with Lewy bodies, and 325 neurologically healthy controls, were genotyped for the H1/H2 haplotype. Subsequently, the two copy number variants that are characteristic of the H1 haplotype were evaluated through a high-resolution approach based on droplet digital polymerase chain reaction, in all H1 homozygous subjects. The H1 allele was significantly overrepresented in all diagnostic groups compared with controls (Parkinson's disease, P = 0.0001; progressive supranuclear palsy, P = 1.22 × 10(-6) ; corticobasal degeneration, P = 0.0002; and dementia with Lewy bodies, P = 0.032). However, no dosage differences were found for any of the two copy number variants analyzed. The H1 haplotype is associated with the risk of several neurodegenerative disorders, including dementia with Lewy bodies. However, common structural diversity within the 17q21.31-H1 clade does not explain this genetic association.
- Published
- 2015
11. P1‐293: IDENTIFICATION OF EXOSOMAL MICRORNAS AS POTENTIAL DIAGNOSTIC BIOMARKERS FOR FRONTOTEMPORAL DEMENTIA
- Author
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Jordi Clarimón, Isabel Sala, Estrella Morenas-Rodríguez, Laia Muñoz-Llahuna, Olivia Belbin, Daniel Alcolea, Katrin Beyer, Maria Carmona-Iragui, Oriol Dols-Icardo, Laura Cervera-Carles, Alberto Lleó, Rafael Blesa, Ignacio Illán-Gala, Ana Gámez-Valero, M. Belen Sánchez-Saudinós, and Juan Fortea
- Subjects
Epidemiology ,business.industry ,Health Policy ,Computational biology ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,microRNA ,Medicine ,Diagnostic biomarker ,Identification (biology) ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Frontotemporal dementia - Published
- 2018
12. Cortical microstructural changes along the Alzheimer's disease continuum
- Author
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Rafael Blesa, Pablo Martinez-Lage, Ainara Estanga, Isabel Sala, Andrea González, María-Belén Sánchez-Saudinos, Maite Garcia-Sebastian, Eduard Vilaplana, Mikel Tainta, Pascual Sánchez-Juan, Mirian Ecay-Torres, Sofía González-Ortiz, Estrella Morenas-Rodríguez, Ane Iriondo, Montserrat Clerigue, Ana Pozueta, Maria Carmona-Iragui, Andrea Izagirre, Daniel Alcolea, Roser Ribosa-Nogué, Jordi Pegueroles, Jordi Clarimón, Juan Fortea, Alberto Lleó, Jorge Villanua, Ofer Pasternak, Victor Montal, Sara Llufriu, Eloy Martinez-Heras, and Ignacio Illán-Gala
- Subjects
0301 basic medicine ,Male ,Amyloid ,medicine.medical_specialty ,Pathology ,Epidemiology ,Alzheimer's disease continuum ,Urology ,CSF ,Disease ,Spinal Puncture ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Apolipoproteins E ,Developmental Neuroscience ,Alzheimer Disease ,Healthy control ,medicine ,Dementia ,Humans ,Cognitive Dysfunction ,Stage (cooking) ,Cognitive impairment ,Aged ,Cerebral Cortex ,medicine.diagnostic_test ,Surrogate endpoint ,Health Policy ,Cortical microstructure ,Magnetic resonance imaging ,Organ Size ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,030104 developmental biology ,Free water ,Disease Progression ,Female ,Neurology (clinical) ,Tau ,Geriatrics and Gerontology ,Psychology ,030217 neurology & neurosurgery ,Biomarkers ,MRI - Abstract
Introduction: Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD). Methods: We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum. Results: Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages. Discussion: These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
- Published
- 2017
13. Relationship Between β-Secretase, Inflammation and Core Cerebrospinal Fluid Biomarkers for Alzheimer's Disease
- Author
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M. Belen Sánchez-Saudinós, Jordi Clarimón, Sofía Antón-Aguirre, Maria Carmona-Iragui, Rafael Blesa, Juan Fortea, Daniel Alcolea, Marc Suárez-Calvet, Alberto Lleó, and Isabel Sala
- Subjects
Male ,Oncology ,medicine.medical_specialty ,tau Proteins ,Inflammation ,Disease ,Sensitivity and Specificity ,Amyloid beta-Protein Precursor ,Cerebrospinal fluid ,Adipokines ,Alzheimer Disease ,Lectins ,Internal medicine ,mental disorders ,medicine ,Humans ,Dementia ,Chitinase-3-Like Protein 1 ,Prospective Studies ,Phosphorylation ,Aged ,Amyloid beta-Peptides ,business.industry ,General Neuroscience ,Neurodegeneration ,General Medicine ,Middle Aged ,medicine.disease ,Peptide Fragments ,Pathophysiology ,Psychiatry and Mental health ,Clinical Psychology ,Frontotemporal Dementia ,β secretase ,Female ,Amyloid Precursor Protein Secretases ,Geriatrics and Gerontology ,medicine.symptom ,Cognition Disorders ,business ,Biomarkers ,Frontotemporal dementia - Abstract
Background Biomarkers in the cerebrospinal fluid (CSF) can track specific pathophysiological pathways underlying Alzheimer's disease (AD). The connection between these biomarkers remains unclear. Objective To study six CSF biomarkers in a clinical cohort of patients with different neurodegenerative conditions. Methods We measured markers of amyloid-β protein precursor (AβPP) processing (Aβ42, sAβPPβ, β-secretase activity), neuronal damage (total tau, p-tau), and inflammation (YKL-40) in CSF from 194 participants with the following diagnoses: subjective cognitive impairment or non-amnestic mild cognitive impairment (na-SCI, n = 44), amnestic mild cognitive impairment (aMCI, n = 45), dementia of the Alzheimer type (DAT, n = 59), frontotemporal dementia (FTD, n = 22), and 24 cognitively normal controls. We compared biomarkers between clinical groups and CSF-profile groups, and we analyzed the correlation between biomarkers. Results CSF levels of sAβPPβ were decreased in FTD patients compared to the other groups. YKL-40 was elevated in DAT and FTD, and also in aMCI patients. CSF Aβ42 correlated positively with β-secretase activity (RS = 0.262) and sAβPPβ (RS = 0.341). CSF YKL-40 correlated positively with total tau (RS = 0.467) and p-tau (RS = 0.429). CSF p-tau and sAβPPβ contributed significantly to distinguish DAT from FTD. Conclusions CSF biomarkers of AβPP processing correlate with each other and are decreased in FTD. The inflammatory marker YKL-40 is increased in different neurodegenerative diseases, even in early stages, and it correlates with biomarkers of neurodegeneration. This suggests that inflammation is a common feature in AD and FTD. A combination of CSF biomarkers tracking distinct pathophysiological processes may be useful to classify subjects with neurodegenerative conditions.
- Published
- 2014
14. The Subjective Cognitive Decline Questionnaire (SCD-Q): A Validation Study
- Author
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Maria A. Mollica, Belen Sanchez, Isabel Sala, José Luis Molinuevo, Magda Castellví, Carmen García-Sánchez, Cinta Valls-Pedret, Judith Saldaña, Lorena Rami, and Jaume Olives
- Subjects
cognition ,Male ,medicine.medical_specialty ,diagnosis ,Disease ,Anxiety ,Neuropsychological Tests ,Sensitivity and Specificity ,memory ,Executive Function ,test ,Alzheimer Disease ,Memory ,Surveys and Questionnaires ,hemic and lymphatic diseases ,medicine ,Humans ,Cognitive Dysfunction ,Effects of sleep deprivation on cognitive performance ,Cognitive decline ,Psychiatry ,Depression (differential diagnoses) ,Aged ,Language ,Depression ,General Neuroscience ,Neuropsychology ,Cognition ,General Medicine ,Alzheimer's disease ,Middle Aged ,Executive functions ,Self Concept ,Psychiatry and Mental health ,Clinical Psychology ,Caregivers ,Female ,Self Report ,Geriatrics and Gerontology ,medicine.symptom ,Cognition Disorders ,Factor Analysis, Statistical ,Psychology ,Clinical psychology - Abstract
Background: Subjective cognitive decline (SCD) is gaining importance as a focus of investigation, but adequate tools are needed for its quantification. Objective: To develop and validate a questionnaire to quantify SCD, termed the Subjective Cognitive Decline Questionnaire (SCD-Q). Methods: 124 controls (CTR), 144 individuals with SCD, 83 mild cognitive impairment subjects, 46 Alzheimer's disease patients, and 397 informants were included. The SCD-Q contains: part I, named MyCog, which is answered by the subject; and part II, TheirCog, which includes the same questions and is answered by the informant or caregiver. The 24 SCD-Q items assess the perceived subjective decline in memory, language, and executive functions in the last two years. Results: The MyCog scores of controls differed significantly from those of the other groups (p < 0.05) and there were significant differences in TheirCog scores between all groups. The optimal TheirCog cut-off score for discriminating between individuals with and without cognitive impairment was 7/24 (sensitivity 85%, specificity 80%). MyCog scores correlated significantly with anxiety and depression (r = 0.29, r = 0.43, p < 0.005), but no correlations were found with neuropsychological tests. TheirCog scores correlated significantly with most of the neuropsychological tests (p < 0.05). Informants' depression and anxiety influenced TheirCog scores in controls and SCD groups. Conclusion: Self-perceived cognitive decline, measured by the SCD-Q part I (MyCog), discriminated SCD from CTR. Part II (TheirCog) was strongly related to subjects' objective cognitive performance, and discriminated between subjects with or without cognitive impairment. The SCD-Q is a useful tool to measure self-perceived cognitive decline incorporating the decliner and the informant perspective.
- Published
- 2014
15. Contents Vol. 26, 2008
- Author
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Hiroshi Tatsumi, Eun A Kim, Reinhard Heun, Wiesje M. van der Flier, Rahul Potluri, Ammar Natalwala, T. Yamada, B. Ibach, Junko Tohyama, Tetsuya Iidaka, Philip Scheltens, Mark Y. Chan, Minna Rusanen, Eini Niskanen, Tsutomu Soma, Rafael Blesa, Yoshie Murata, M. Waragai, Marinus A. Blankenstein, Tuija Kangasmaa, Chang Hyung Hong, Nicolaas A. Verwey, Jyrki T. Kuikka, Sharon F.M. Bouwens, Frans R.J. Verhey, Miia Kivipelto, Shutaro Nakaaki, Toshiya Fukui, Wee Shiong Lim, Kang Soo Lee, Teresa Gomez-Isla, Masaru Mimura, Alberto Lleó, H. Matsuda, Jordi Clarimón, Hilkka Soininen, Sandra D. Mulder, Anne M. Jauhiainen, Junko Sato, Yoshihiro Shinagawa, M.W. Riepe, Alie Schuitemaker, Susanna Tervo, Hardeep Uppal, Ignasi Gich, Caroline M. van Heugten, Toshiaki A. Furukawa, Ritva Vanninen, Isabel Sala, Francisco Blanco-Vaca, Laura Molina-Porcel, Cees Mulder, C. Erik Hack, Robert Veerhuis, S. Mizumura, Suresh Sahadevan, Estela Lázaro, Jin Hongo, Hae-Kwan Cheong, Maria Belén Sánchez-Saudinós, Byoung Hoon Oh, and Dong-Woo Lee
- Subjects
Psychiatry and Mental health ,Cognitive Neuroscience ,Geriatrics and Gerontology - Published
- 2008
16. Homocysteine and Cognitive Impairment
- Author
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Jordi Clarimón, Rafael Blesa, Laura Molina-Porcel, Alberto Lleó, Teresa Gomez-Isla, Ignasi Gich, Isabel Sala, Estela Lázaro, Francisco Blanco-Vaca, and Maria Belén Sánchez-Saudinós
- Subjects
medicine.medical_specialty ,Homocysteine ,Cognitive Neuroscience ,Cognitive disorder ,Neuropsychology ,medicine.disease ,Developmental psychology ,Central nervous system disease ,Psychiatry and Mental health ,chemistry.chemical_compound ,Degenerative disease ,chemistry ,Internal medicine ,Cardiology ,medicine ,Dementia ,Geriatrics and Gerontology ,Risk factor ,Alzheimer's disease ,Psychology - Abstract
Background/Aims: Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular and cerebrovascular disease, and it has also been proposed as an independent risk factor for dementia and Alzheimer’s disease (AD). Its relationship with cognitive impairment, however, remains unclear. We aimed to determine the relationship of tHcy levels with clinical diagnoses and cognitive performance in a sample of outpatients with cognitive impairment. Methods: Plasma tHcy, folate, vitamin B12 and creatinine levels were assessed in individuals evaluated at the Memory Disorder Unit. Diagnoses included subjective memory complaints (SMC, n = 27), mild cognitive impairment (MCI, n = 142), AD (n = 139) and vascular dementia (VD, n = 17). All patients underwent extensive neuropsychological testing to evaluate attention, memory, language, and visuoconstructional and executive functions, as well as depression and impairments of daily living activities. Results: tHcy levels did not differ between patients with SMC, MCI, AD or VD. Increased tHcy was associated with worse performance in geometric figure copy and clock drawing tests. Conclusions: tHcy levels did not discriminate between diagnostic groups of patients with cognitive impairments. Elevated tHcy levels in these patients appear to have a detrimental effect on visuoconstructional performance.
- Published
- 2008
17. IC‐P‐217: CSF β‐AMYLOID AND PHOSHO‐TAU INTERACTIONS ON BRAIN STRUCTURE IN PRECLINICAL AD
- Author
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Juan Fortea, Eduard Vilaplana, Daniel Alcolea, Maria Carmona‐Iragui, Maria Belén Sánchez‐Saudinós, Isabel Sala, Sofía Antón‐Aguirre, Sofía González‐Ortiz, Santiago Medrano, Jordi Pegueroles, Estrella Morenas, Jordi Clarimón, Rafael Blesa, and Alberto Lleó
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
18. P2‐088: RELATIONSHIP BETWEEN CSF YKL‐40 AND CORTICAL THICKNESS
- Author
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Sofía González-Ortiz, Estrella Morenas, Juan Fortea, Alberto Lleó, Maria Belén Sánchez-Saudinós, Daniel Alcolea, Rafael Blesa, Isabel Sala, Santiago Medrano, Jordi Clarimón, Maria Carmona-Iragui, Sofía Antón-Aguirre, and Eduard Vilaplana
- Subjects
Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2014
19. P2‐132: BIOMARKERS IN CEREBRAL AMYLOID ANGIOPATHY‐RELATED INFLAMMATION
- Author
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Isabel Sala, Sofía Antón-Aguirre, Ana Fernández-Arcos, Daniel Alcolea, Rafael Blesa, Alberto Lleó, Maria Carmona-Iragui, Fabrizio Piazza, Beatriz Gómez-Ansón, Juan Fortea, Jordi Clarimón, Oriol Dols-Icardo, Estrella Morenas-Rodríguez, Valle Camacho, and Josep Munuera
- Subjects
Pathology ,medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Inflammation ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Neurology (clinical) ,Cerebral amyloid angiopathy ,Geriatrics and Gerontology ,medicine.symptom ,business - Published
- 2014
20. P3‐230: CSF β‐AMYLOID AND PHOSHO‐TAU INTERACTIONS ON BRAIN STRUCTURE IN PRECLINICAL AD
- Author
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Maria Carmona-Iragui, Estrella Morenas, Eduard Vilaplana, Juan Fortea, Daniel Alcolea, Rafael Blesa, Isabel Sala, Sofía Antón-Aguirre, Sofía González-Ortiz, Alberto Lleó, Maria Belén Sánchez-Saudinós, Santiago Medrano, Jordi Clarimón, and Jordi Pegueroles
- Subjects
medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Fluid-attenuated inversion recovery ,medicine.disease ,Hyperintensity ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Clinical research ,Developmental Neuroscience ,Rating scale ,Interquartile range ,Medicine ,Dementia ,Neurology (clinical) ,Radiology ,Geriatrics and Gerontology ,Cognitive decline ,Occipital lobe ,business - Abstract
clinical characteristics of probable CAA based on Boston’s criteria and also investigated predictive factors associated with certain features of CAA. Methods: We retrospectively reviewed patients diagnosed as probable CAA based on the Boston’s criteria who underwent MRI, including gradient echo (GRE) andfluid attenuated inversion recovery (FLAIR) images and clinical assessment fromAugust 2006 toMay 2013.AllGRE images of each subject were reviewed by 1 rater to describe the location and numbers of intracranial hemorrhages. The white matter hyperintensity was rated based on rating scales proposed by Clinical Research Center for Dementia of South Korea (CREDOS). Statistical analyses were performed using SPSS version 21.0 and SAS 6.0.Results: A total of 92 patients were included in this study. Themean age of onsetwas 68.669.9years (M:F1⁄461:31). Sixty-three patients (68%) had hypertension. The initial diagnoses included cognitive impairment (48 patients, 52%), lobar ICH (14 patients, 15.2%), and lacunar infarction (10 patients, 10.9%). Thirty-nine patients had deep microbleeds. Fifty-three patients (57%) showed posterior dominant distribution (parietal and occipital lobe) of hemorrhages. Themedian number of microbleeds was 15 [interquartile range (IQR): 7-41.33]. Patients with posterior dominant location were older (p 1⁄40.028) and complained of cognitive decline more often (p 1⁄40.034). This group had more microbleeds (p1⁄40.006) and showed more severewhitematter hyperintensities (p1⁄40.008). They also tended to have lower recall score of MMSE than the other group. Patients with deep microbleeds showed more severe white matter hyperintensities (p 1⁄40.002). Twenty-four patients performed follow-up MR imaging. The mean interval time was 28.6624.2 months. Large number of microbleeds at baseline was associated with increasing rate of newmicrobleeds at follow-up scan.Conclusions:We found the impact of location of intracranial hemorrhages on cognitive impairment andwhitematter hyperintensities in patientswithCAA.Thedistribution and the number of microbleeds at baseline were factors associated with disease progression. These data indicate that early evaluation of the location and number of microbleeds can be helpful to assess clinical characteristics and prognosis in patients with probable CAA.
- Published
- 2014
21. Rapidly Progressive Dementia Experience in a Tertiary Care Medical Center
- Author
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Alberto Lleó, Beatriz Gómez-Ansón, Marta Marquié, Isabel Sala, Maria Belén Sánchez-Saudinós, Daniel Alcolea, Rafael Blesa, Teresa Gomez-Isla, and Raquel Sánchez-Valle
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Referral ,prion disease ,Disease ,Tertiary care ,Creutzfeldt-Jakob Syndrome ,rapidly progressive dementia ,Tertiary Care Centers ,mental disorders ,medicine ,Humans ,Dementia ,Medical diagnosis ,Vascular dementia ,Aged ,cognitive impairment ,Rapidly progressive dementia ,business.industry ,Dementia, Vascular ,Neurodegenerative Diseases ,14-3-3 protein ,neurodegenerative dementia ,medicine.disease ,Creutzfeldt-Jakob disease ,Surgery ,Psychiatry and Mental health ,Clinical Psychology ,Disease Progression ,Female ,Geriatrics and Gerontology ,business ,Gerontology - Abstract
Diagnosis of rapidly progressive dementia (RPD) poses a complex medical challenge that requires an exhaustive evaluation. Although prion diseases, in particular Creutzfeldt-Jakob disease (CJD), are often suspected, many other nonprion diseases may present as RPD. Our aim was to review the causes of RPD in our center to better understand the underlying conditions. We reviewed clinical, neuroimaging, and cerebrospinal fluid data from patients with RPD admitted to our hospital from 1994 to 2009. Forty-nine patients (mean age at onset 72.4 y) with RPD were admitted to our center during the study period. The mean interval between the onset of symptoms and admission was 4.6 months. The final clinical diagnoses were as follows: nonprion neurodegenerative diseases (36.8%), CJD (30.6%), vascular dementia (8.2%), toxic-metabolic conditions (8.2%), and other disorders (16.2%). Among cases with informed death (n = 19), the average survival time was 8.6 +/- 9.5 months. Survival was shorter among patients with prion disease (n = 10) than in those with other diagnoses (n = 9, P = 0.004). In conclusion, nonprion neurodegenerative diseases are the most common cause of RPD in our center. Our results suggest that although CJD is often suspected as a cause of RPD, its frequency depends on the referral differences across specialized centers
- Published
- 2012
22. Subject Index Vol. 26, 2008
- Author
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Yoshihiro Shinagawa, Jyrki T. Kuikka, Robert Veerhuis, Teresa Gomez-Isla, Hae-Kwan Cheong, Maria Belén Sánchez-Saudinós, Toshiya Fukui, Anne M. Jauhiainen, Minna Rusanen, Shutaro Nakaaki, Jordi Clarimón, Yoshie Murata, Byoung Hoon Oh, Chang Hyung Hong, Dong-Woo Lee, Wee Shiong Lim, Frans R.J. Verhey, Estela Lázaro, Alberto Lleó, Masaru Mimura, Isabel Sala, C. Erik Hack, Philip Scheltens, M.W. Riepe, Reinhard Heun, Junko Sato, Eini Niskanen, Jin Hongo, Francisco Blanco-Vaca, S. Mizumura, Suresh Sahadevan, Tsutomu Soma, Kang Soo Lee, Hiroshi Tatsumi, Nicolaas A. Verwey, Laura Molina-Porcel, Susanna Tervo, Hardeep Uppal, Ritva Vanninen, Sandra D. Mulder, Hilkka Soininen, Caroline M. van Heugten, Junko Tohyama, Alie Schuitemaker, T. Yamada, Ignasi Gich, Sharon F.M. Bouwens, Miia Kivipelto, Tetsuya Iidaka, Rafael Blesa, Mark Y. Chan, M. Waragai, Marinus A. Blankenstein, Tuija Kangasmaa, Toshiaki A. Furukawa, Cees Mulder, Eun A Kim, Wiesje M. van der Flier, Rahul Potluri, Ammar Natalwala, H. Matsuda, and B. Ibach
- Subjects
Gerontology ,Psychiatry and Mental health ,Psychoanalysis ,Index (economics) ,Cognitive Neuroscience ,Subject (documents) ,Geriatrics and Gerontology ,Psychology - Published
- 2008
23. Reelin Signaling Pathway Genotypes and Alzheimer Disease in a Spanish Population
- Author
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Rafael Blesa, Santiago Bernades, Lluís Tomàs-Abadal, Isabel Sala-Matavera, Teresa Puig, Josep Abós, Sofia Antón, Enric Bufill, Jordi Clarimón, Pere Roura-Poch, Alberto Lleó, and Belén Sánchez-Saudinós
- Subjects
Oncology ,Male ,medicine.medical_specialty ,Genotype ,Cell Adhesion Molecules, Neuronal ,Nerve Tissue Proteins ,Protein Serine-Threonine Kinases ,Polymorphism, Single Nucleotide ,single nucleotide polymorphisms ,mild cognitive impairment ,Polymorphism (computer science) ,Alzheimer Disease ,Internal medicine ,reelin ,medicine ,Humans ,Cognitive Dysfunction ,Genetic variability ,Reelin ,Allele frequency ,Aged ,Genetics ,Extracellular Matrix Proteins ,synaptic plasticity ,biology ,business.industry ,Serine Endopeptidases ,epigenetic changes ,Case-control study ,Odds ratio ,medicine.disease ,CAMK2A ,Psychiatry and Mental health ,Clinical Psychology ,Reelin Protein ,Spain ,Case-Control Studies ,biology.protein ,Female ,Geriatrics and Gerontology ,Alzheimer's disease ,Alzheimer disease ,PLK2 ,business ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,Gerontology ,Signal Transduction - Abstract
Background: Several reports suggest that the reelin protein could play a role in Alzheimer pathophysiology. This led us to ask whether genetic variability in the reelin pathway may increase the risk of developing Alzheimer disease (AD) or mild cognitive impairment (MCI). Methods: This was a case-control study in which neuropsychological tests were administered and peripheral blood samples taken. The study included 121 patients with AD, 94 with MCI, and 198 controls. Forty biallelic variants single nucleotide polimorphisms were genotyped in 8 genes related to reelin signaling pathway using a SNPlex genotyping system, and allele frequencies were compared between patients and controls using chi(2) tests and obtaining odds ratios (OR). Results: A total of 413 subjects with complete neuropsychological data were analyzed. A significant association between the genotypes RELN (rs528528 and rs2299356), PLK2 (rs15009 and rs702723), and CAMK2A (rs3756577 and rs3822606) and AD or MCI was found. A significant association also was found between the GG genotype at the RELN-rs2299356 and the risk of AD (OR = 2.68, P = 0.003) and between the AG genotype at the CAMK2A-rs3822606 (OR = 2.13, P = 0.004). We found a protective effect of the RELN-rs528528 CT genotype and MCI (OR = 0.36, P = 0.002), and the PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 with OR ranging from 0.40 to 0.57 on AD. These data suggest that TT or CT genotypes at CAMK2A-rs3756577 is associated with risk reduction for AD and MCI ranging from 2 to nearly 8 times. Conclusions: Our data suggest a possible relation between certain reelin signaling pathway genotypes and cognitive impairment related to AD.
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