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1. The mediating role of reflective functioning in the association between childhood trauma and suicide attempt

Author

Palao-Tarrero, A., Vicente, L., Velasco, M., Orgaz, B., García, D., Vieta, E., Vázquez, M., Bracco, L., Gómez-Vallejo, S., Díaz, C., Palao, D.J., Comendador, L., Punti, J., Muñoz, M.T., García- Ramos, A., Ayad-Ahmed, W., Diaz-Carracedo, P., Ayuso-Mateos, J.L., Jimenez-Treviño, L., Bobes-Bascarán, M.T., Seijo-Zazo, E., Fernandez-Fernandez, J., Garcia-Fernandez, A., Canal-Rivero, M., Rider, J., Reguera, P., Puertas, M., García-Ligero, E., Tur, N., Navas, M., Saiz-Gonzalez, D., Carrasco, J.L., Andreo-Jover, J., Curto Ramos, J., Bobes, J., Bravo-Ortiz, M., Cebria, A.I., Crespo-Facorro, B., De la Torre-Luque, A., Díaz-Marsa, M., Fernández-Rodrigues, V., Garrido-Torres, N., Grande, I., López Peña, M.P., Pemau, A., Roberto, N., Ruiz-Veguilla, M., Saiz, P., Rodríguez-Vega, B., and Pérez-Sola, V.

Published
2024
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4. The mediating role of reflective functioning in the association between childhood trauma and suicide attempt

Author

Andreo-Jover, J., primary, Curto Ramos, J., additional, Bobes, J., additional, Bravo-Ortiz, M., additional, Cebria, A.I., additional, Crespo-Facorro, B., additional, De la Torre-Luque, A., additional, Díaz-Marsa, M., additional, Fernández-Rodrigues, V., additional, Garrido-Torres, N., additional, Grande, I., additional, López Peña, M.P., additional, Pemau, A., additional, Roberto, N., additional, Ruiz-Veguilla, M., additional, Saiz, P., additional, Rodríguez-Vega, B., additional, Pérez-Sola, V., additional, Palao-Tarrero, A., additional, Vicente, L., additional, Velasco, M., additional, Orgaz, B., additional, García, D., additional, Vieta, E., additional, Vázquez, M., additional, Bracco, L., additional, Gómez-Vallejo, S., additional, Díaz, C., additional, Palao, D.J., additional, Comendador, L., additional, Punti, J., additional, Muñoz, M.T., additional, García- Ramos, A., additional, Ayad-Ahmed, W., additional, Diaz-Carracedo, P., additional, Ayuso-Mateos, J.L., additional, Jimenez-Treviño, L., additional, Bobes-Bascarán, M.T., additional, Seijo-Zazo, E., additional, Fernandez-Fernandez, J., additional, Garcia-Fernandez, A., additional, Canal-Rivero, M., additional, Rider, J., additional, Reguera, P., additional, Puertas, M., additional, García-Ligero, E., additional, Tur, N., additional, Navas, M., additional, Saiz-Gonzalez, D., additional, and Carrasco, J.L., additional

Published
2024
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8. Depressive predominant polarity in bipolar disorder – a retrospective study in a sample of patients hospitalized for a manic episode

Author

Bracco, L., primary, Gracia, H. Andreu, additional, De Juan Viladegut, O., additional, Mayorga, L. Olivier, additional, Recio, I. Ochandiano, additional, Salmeròn, S., additional, Sanya, L. Bueno, additional, Plaza, T. Fernàndez, additional, Palomo, A. Gimènez, additional, Pacchiarotti, I., additional, and Vieta, E., additional

Published
2023
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9. Antidepressants as predictors of relapse in bipolar disorders

Author

De Juan Viladegut, O., primary, Gracia, H. Andreu, additional, Olivier Mayorga, L., additional, Fernández Plaza, T., additional, Ochandiano Recio, I., additional, Salmerón, S., additional, Bueno Sanya, L., additional, Bracco, L., additional, Giménez Palomo, A., additional, and Pacchiarotti, I., additional

Published
2023
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19. Metabolic interaction between ApoE genotype and onset age in Alzheimer's disease: implications for brain reserve

Author

Mosconi, L., Herholz, K., Prohovnik, I., Nacmias, B., De Cristofaro, M.T.R., Fayyaz, M., Bracco, L., Sorbi, S., and Pupi, A.

Subjects
Genotype -- Research, Age factors in disease -- Development and progression, Age factors in disease -- Medical examination, Age factors in disease -- Research, Alzheimer's disease -- Development and progression, Alzheimer's disease -- Medical examination, Alzheimer's disease -- Research, Health, Psychology and mental health
Published
2005

20. Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease

Author

Mosconi, L., Nacmias, B., Sorbi, S., De Cristofaro, M.T.R., Fayazz, M., Tedde, A., Bracco, L., Herholz, K., and Pupi, A.

Subjects
Alzheimer's disease -- Research -- Genetic aspects -- Physiological aspects, Health, Psychology and mental health, Physiological aspects, Research, Genetic aspects
Abstract

J Neurol Neurosurg Psychiatry 2004;75:370-376 Objectives: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes [...]

Published
2004

22. PER2 C111G polymorphism, cognitive reserve and cognition in subjective cognitive decline and mild cognitive impairment: a 10‐year follow‐up study

Author

Bessi, V., primary, Giacomucci, G., additional, Mazzeo, S., additional, Bagnoli, S., additional, Padiglioni, S., additional, Balestrini, J., additional, Tomaiuolo, G., additional, Piaceri, I., additional, Carraro, M., additional, Bracco, L., additional, Sorbi, S., additional, and Nacmias, B., additional

Published
2020
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25. The role of cannabis in bipolar disorder relapse: a prospective study of hospital acute readmissions.

Author

Olivier, L., Giménez, A., Andreu Gracia, H., Bueno, L., De Juan Viladegut, Ó., Fernández, T. M., Ochandiano, I., Salmerón, S., Bracco, L., Tardón Senabre, L., and Pacchiarotti, I.

Subjects
MARIJUANA abuse, SCHIZOAFFECTIVE disorders, PATIENT readmissions, PSYCHIATRIC treatment, ELECTROCONVULSIVE therapy
Abstract

Introduction: With the rapid changes of attitude, investigation and legislation around cannabis and its subproducts in the Western world, there is a need to profoundly examine the consequences of its use in the general population and, specifically, in people affected by mental disorders. There is a clear relationship between cannabis use and psychosis, but there is also growing evidence of its relationship with manic episodes (Sideli et al, 2019). A systematic review published by the CANMAT Task Force in 2022 examined again the relationship between cannabis use and bipolar disorder (BD), establishing association with worsened course and functioning of BD in frequent users (Tourjman et al., 2023). On the other hand, some recent papers have highlighted the role of the endocannabinoid system (ECS) in BD, suggesting even possible beneficial effects, mainly through the CB2 receptor (Arjmand et al, 2019). Objectives: To describe the impact of cannabis in the psychiatric readmission in BD and to approach the differences in course in cannabis users with regards to non-users. Methods: We conducted a prospective cohort study including the patients admitted to our acute psychiatric unit with the diagnosis of manic or mixed episode during the period between 2015 and 2019 (including patients with one of both final diagnosis: BD or schizoaffective disorder). We established a follow-up of 3 years from the date of admission in which hospital readmissions are examined. Results: The study, which included 309 patients, concluded that cannabis users were admitted and had the first episode at a younger age (p=0.005), a higher percentage of them did not have a previous diagnosis (p=0.026) nor a previous history of mental health issues (p=0.019) and it was more likely to be their first admission (p=0.011) and to suffer psychotic symptoms (p=0.002). As of treatment, the results were statistically significant regarding the fact that a lower proportion of patients had received previous psychiatric treatment (p=0.004) and previous electroconvulsive therapy (p=0.003). There was a higher chance of them being non-adherent with medication (p<0.001) and to be administered extended-release antipsychotic treatment during admission (p<0.001). The study did not find a statistically significant relationship with cannabis use and a higher rate of readmission in the 3 years of follow-up. Conclusions: Although a higher relapse rate could not be proven in our study, other previously identified factors related to a worse illness course (Sajatovic et al., 2009) did show a significant association with cannabis use, which could lead to one suggesting that our results are compatible with the actual evidence and that cannabis products are detrimental to people who suffer from BD and schizoaffective disorder. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Published
2024
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26. Interplay of Environmental Factors, Genetic Susceptibility, and Sleep Disturbances predict Bipolar Disorder's Relapses: preliminary results from a pilot study.

Author

Bort, M., Fico, G., Oliva, V., de Prisco, M., Bracco, L., Possidente, C., Rivas, M. Y., Ruiz, V., Montejo, L., Vieta, E., and Murru, A.

Subjects
SLEEP interruptions, AIR pollutants, METEOROLOGICAL stations, CIRCADIAN rhythms, AIR pollution
Abstract

Introduction: Predicting acute affective episodes in individuals with Bipolar Disorder (BD) remains a clinical challenge. Specific environmental stressors, including air pollution, noise, and temperature variations might worsen affective symptoms or sleep in the general population, but their role in BD relapses is often overlooked. Indeed, they might exacerbate BD by perturbing circadian rhythms – fundamental aspects of BD. Objectives: We thereby present the protocol of this pilot study and future preliminary data. We aim to longitudinally assess sleep alterations, mood fluctuations, and environmental exposure to several factors (air pollutants, climate, noise, artificial light-at-night, green space access) in patients with BD and to check the association of these variables with BD relapses. Methods: In this pilot study, we will recruit 40 patients with BD in a 6-month prospective study. Patients were assessed during baseline, at 3 and 6 months. Data recollected will consist of a subjective (questionnaires) and objective (through meteorological stations) evaluation of physical environmental factors around the home residence; clinical assessment of mood and circadian rhythms, and continuous tracking of sleep-wake patterns, energy, and movement using actigraphy. Results: Expected results will show that exposure to a worse environment (higher pollution, noise, light exposure, climate) will be associated with worse BD outcomes (i.e., relapse, mood symptoms, sleep alterations). Conclusions: We will be sharing preliminary data from our ongoing study, offering insights into early patterns and findings that shed light on our objectives. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Published
2024
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27. The relationship between sleep problems and suicidality in Bipolar Disorder: a Systematic Review and a Meta-analysis.

Author

Possidente, C., Bort, M., De Prisco, M., Oliva, V., Fico, G., Bracco, L., Sommerhoff, C., Montejo, L., Murru, A., and Vieta, E.

Subjects
SLEEP interruptions, SLEEP, SLEEP quality, ATTEMPTED suicide, SUICIDAL ideation
Abstract

Introduction: Bipolar disorder (BD) is a multifaceted illness encompassing mood, energy, cognitive and biorhythms alterations. Sleep disturbances are common in prodromic, acute and inter-episodic phases of BD. Suicidality presents a known association with sleep disturbances. However, their interplay in BD remains intricate and not fully elucidated. Objectives: The aim of the present systematic review (SR) and meta-analysis (MA) is to summarise the available evidence and to provide an estimate of the association between sleep disturbances and suicidality, defined as presence of suicide ideation, behaviour and suicide attempts, in patients with BD. Methods: We conducted a comprehensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, PsycINFO, and SCOPUS databases. We included all studies reporting an association between sleep problems and suicidal behaviour in BD patients. No language restriction was imposed. Effect sizes were calculated as odds ratio (OR) for dichotomic variables, standard mean difference (SMD) for continuous outcomes, and Spearman's coefficient (r) for correlations. Heterogeneity was assessed using the I2 statistic. Global inconsistency was evaluated using the Q statistics with the corresponding p-value. Results: The initial search yielded 911 unique abstracts, of which 62 underwent full-text screening. Fourteen publications were included, comprising twelve cross-sectional and two longitudinal studies. The total sample consisted of 19,601 subjects diagnosed with BD, of which 51.76% were females and 69.52% had a diagnosis of BD type 1. We found that people with BD and sleep disturbances tend to have higher suicidality, both current (SMD=0.79, 95%CI=0.53, 1.05) and lifetime (OR=1.8; 95%CI=1.41, 2.55), when compared with people with BD and no sleep disturbances. Additionally, patients with BD and a history of suicide attempts tend to have more sleep problems (OR=1.37, 95%CI=1.21, 1.55). Moreover, a positive correlation exists between suicidality and poor sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) (r= 0.24, 95%CI=0.10, 0.36). No heterogeneity was found, except in the subanalysis of correlation (I2=66.67%, Q p-value=0.01). Conclusions: Our SRMA outlines a positive relation between sleep disturbances and suicidality in patients with BD. The small number of included studies and the scarcity of longitudinal studies, preventing the inference of a causal relationship, represent the major limitations of this study. Also, studies with objective measures of sleep alterations are currently lacking. The prompt recognition, objective measurement, and treatment of sleep alterations could be crucial in averting or reducing suicidal attempts in BD. Disclosure of Interest: C. Possidente: None Declared, M. Bort: None Declared, M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: Fellowship from "La Caixa" Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), L. Bracco: None Declared, C. Sommerhoff: None Declared, L. Montejo: None Declared, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672, PI22/00840) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER), E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdireccio ́n General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). [ABSTRACT FROM AUTHOR]

Published
2024
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28. PER2 C111G polymorphism, cognitive reserve and cognition in subjective cognitive decline and mild cognitive impairment: a 10‐year follow‐up study.

Author

Bessi, V., Giacomucci, G., Mazzeo, S., Bagnoli, S., Padiglioni, S., Balestrini, J., Tomaiuolo, G., Piaceri, I., Carraro, M., Bracco, L., Sorbi, S., and Nacmias, B.

Subjects
MILD cognitive impairment, EXECUTIVE function, CLOCK genes, SLEEP-wake cycle, NEUROPSYCHOLOGICAL tests, ALZHEIMER'S disease
Abstract

Background and purpose: CLOCK and PER2 genes have been implicated in sleep–wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. Methods: Sixty‐eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow‐up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD‐c and MCI‐c) and non‐converters (SCD‐nc, MCI‐nc) were considered. Results: CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non‐carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow‐up, two SCD and 15 MCI subjects progressed to AD: both of the SCD‐c subjects presented the PER2 G allele, while none of the SCD PER2 G non‐carriers converted to AD (P = 0.003). Conclusion: PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD. [ABSTRACT FROM AUTHOR]

Published
2021
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30. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Author

Lambert, J. C., Ibrahim-Verbaas, C. A., Russo, G., Mayhaus, M., Lannefelt, L., Hakonarson, H., Pichler, S., Carrasquillo, M. M., Ingelsson, M., Beekly, D., Alvarez, V., Zou, F., Valladares, O., Thorton-Wells, T. A., Younkin, S. G., Coto, E., Hamilton-Nelson, K. L., Gu, W., Razquin, C., Pastor, P., Mateo, I., Owen, M. J., Faber, K. M., Jonsson, P. V., Jones, N., Combarros, O., O'Donovan, M. C., Cantwell, L. B., Soininen, H., Blacker, D., Mead, S., Mosley, T. H., Bennett, D. A., Harris, T. B., Fratiglioni, L., Smith, A. V., Holmes, C., de Bruijn, R. F., Passmore, P., Montine, T. J., Bettens, K., Rotter, J. I., Brice, A., Morgan, K., Foroud, T. M., Kukull, W. A., Chouraki, V., Hannequin, D., Powell, J. F., Nalls, M. A., Ritchie, K., Lunetta, K. L., Kauwe, J. S., Boerwinkle, E., Riemenschneider, M., Boada, M., Hiltuenen, M., Thomas, C., Martin, E. R., Schmidt, R., Rujescu, D., Wang, L. S., Dartigues, J. F., Mayeux, R., Tzourio, C., Hofman, A., Nöthen, M. M., Graff, C., Ikram, M. A., Psaty, B. M., Jones, L., Haines, J. L., Holmans, P. A., Lathrop, M., Pericak-Vance, M. A., Launer, L. J., Farrer, L. A., van Duijn, C. M., Van Broeckhoven, C., Zelenika, D., Moskvina, V., Seshadri, S., Williams, J., Schellenberg, G. D., Amouyel, P., Alpérovitch, A., Boland, A., Delépoine, M., Dubois, B., Duron, E., Vardarajan, B. N., Epelbaum, J., Van Cauwenberghe, C., Engelborghs, S., Vandenberghe, R., De Deyn, P. P., Ferri, R., Romano, C., Caltagirone, C., Orfei, M. D., Ciaramella, A., Kamatani, Y., Scarpini, E., Fenoglio, C., Siciliano, G., Bonuccelli, U., Bagnoli, S., Bracco, L., Bessi, V., Cecchetti, R., Bastgiani, P., Squassina, A., Harold, D., Lin, C. F., Seripa, D., Frank-García, A., Sastre, I., Blesa, R., Alcolea, D., Suárez-Clavet, M., Sánchez-Juan, P., Muñoz Fernandez, C., Aladro Benito, Y., Thonberg, H., Gerrish, A., Forshell, C., Lilus, L., Kinhult-Ståhlbom, A., Giedraitis, V., Kilander, L., Brundin, R. M., Concari, L., Helisalmi, S., Koivisto, A. M., Haapasalo, A., Schmidt, H., Solfrizzi, V., Frisardi, V., Ott, J., Carney, R. M., Mash, D. C., Albert, M. S., Albin, R. L., Apostolova, L. G., Arnold, S. E., Barmada, M. M., Kunkle, B., Barnes, L. L., Beach, T. G., Bigio, E. H., Bird, T. D., Boeve, B. F., Bowen, J. D., Boxer, A., Burk, J. R., Cairns, N. J., Cao, C., Dunstan, M. L., Carlson, C. S., Carroll, S. L., Chibnik, L. B., Chui, H. C., Clark, D. G., Corneveaux, J., Cribbs, D. G., DeCarli, C., DeKosky, S. T., Demirci, F. Y., Ruiz, A., Dick, M., Dickson, D. W., Duara, R., Ertekin-Taner, N., Fallon, K. B., Farlow, M. R., Ferris, S., Frosch, M. P., Galasko, G. R., Ganguli, M., Bihoreau, M. T., Gearing, M., Geschwind, D. H., Ghetti, B., Gilman, S., Glass, J. D., Growdon, J. H., Hamilton, R. L., Harrell, L. E., Head, E., Honig, L. S., Choi, S. H., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Jicha, G. A., Jin, L. W., Karydas, A., Kaye, J. A., Kim, R., Koo, E. H., Reitz, C., Kowall, N. W., Kramer, J. H., Kramer, P., LaFerla, F. M., Lah, J. J., Levernez, J. B., Levey, A. I., Li, G., Lieberman, A. P., Lyketsos, C. G., Pasquier, F., Mack, W. J., Marson, D. C., Martiniuk, F., Masliah, E., McCormick, W. C., McCurry, S. M., McDavid, A. N., McKee, A. C., Mesulam, M., Miller, B. L., Naj, A. C., Cruchaga, C., Miller, C. A., Miller, J. W., Morris, J. C., Murrell, J. R., Olichney, J. M., Pankratz, V. S., Parasi, J. E., Peskind, E., Peterson, R. C., Pierce, A., Craig, D., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Raiman, E. M., Reisberg, B., Ringman, J. M., Roberson, E. D., Rosen, H. J., Amin, N., Rosenberg, R. N., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seely, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Berr, C., Tanzi, R. E., Trojanowski, J. Q., Troncoso, J. C., Van Deerlin, V. M., Van Eldik, L. J., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh-Bohmer, K. A., Williamson, J., Lopez, O. L., Woltjer, R. L., Yu, C. E., Barber, R., Au, R., Wolf, P. A., Beiser, A., Debette, S., Yang, Q., Weinstein, G., Johnson, A. D., De Jager, P. L., Wang, J., Uitterlinden, A. G., Rivadeneira, F., Koudstgaal, P. J., Longstreth, W. T., Becker, J. T., Kuller, L. H., Lumley, T., Rice, K., Garcia, M., Deramecourt, V., Aspelund, T., Marksteiner, J. J., Dal-Bianco, P., Töglhofer, A. M., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A. M., Bressler, J., Breteler, M. M., Johnston, J. A., Fornage, M., Hernández, I., Rosende Roca, M., Ana Mauleón, M., Alegrat, M., RamÍrez-Lorca, R., González-Perez, A., Chapman, J., Stretton, A., Morgan, A., Evans, D., Kehoe, P. G., Medway, C., Lord, J., Turton, J., Hooper, N. M., Vardy, E., Warren, J. D., Schott, J. M., Uphill, J., Ryan, N., Lovestone, S., Rossor, M., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Sims, R., Letenneur, L., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffman, P., Kornhuber, J., Morón, F. J., Feulner, T., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A. D., Warden, D., Wilcock, G., Heuser, I., Wiltgang, J., Rubinsztein, D. C., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N. J., Gurling, H., McQuillen, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Eiriksdottir, G., Shaw, C. E., Singleton, A. B., Guerreiro, R., Jöckel, K. H., Klopp, N., Wichmann, H. E., Graff-Radford, N. R., Ma, L., Bisceglio, G., Sleegers, K., Fisher, E., Warner, N., Pickering-Brown, S., Becker, Tim, Goate, A. M., Fiévet, N., Huentelman, M. W., Gill, M., Brown, K., Bellenguez, C., Kamboh, M. I., Keller, L., Barberger-Gateau, P., McGuiness, B., Larson, E. B., Green, R., Myers, A. J., Dufouil, C., Todd, S., Wallon, D., DeStafano, A. L., Love, S., Rogaeva, E., Gallacher, J., St George-Hyslop, P., Clarimon, J., Lleo, A., Bayer, A., Tsuang, D. W., Yu, L., Tsolaki, M., Bis, J. C., Bossù, P., Spalletta, G., Proitsi, P., Collinge, J., Sorbi, S., Sanchez-Garcia, F., Fox, N. C., Hardy, J., Deniz Naranjo, M. C., Bosco, P., Beecham, G. W., Clarke, R., Brayne, C., Galimberti, D., Mancuso, M., Matthews, F., Initiative, European Alzheimer's Disease, Disease, Genetic and Environmental Risk in Alzheimer's, Consortium, Alzheimer's Disease Genetic, Epidemiology, Cohorts for Heart and Aging Research in Genomic, Moebus, S., Grenier-Boley, B., Mecocci, P., Del Zompo, M., Maier, W., Hampel, H., Pilotto, A., Bullido, M., Panza, F., Caffarra, P., Nacmias, B., Gilbert, J. R., Neurology, Radiology & Nuclear Medicine, and Epidemiology

Subjects
Male, Apolipoprotein E, epidemiology [Alzheimer Disease], SORL1, Medizin, genetics [Alzheimer Disease], Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, PICALM, Cohort Studies, Alzheimer Disease, ddc:570, PSEN2, Genetics, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, Aged, Genetic association, Aged, 80 and over, Middle Aged, medicine.disease, Genetic Loci, Case-Control Studies, Female, Human medicine, Alzheimer's disease, statistics & numerical data [Genome-Wide Association Study], Genome-Wide Association Study
Abstract

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Published
2013
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35. The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study

Author

Mascalchi, M, Ginestroni, A, Toschi, N, Poggesi, A, Cecchi, P, Salvadori, E, Tessa, C, Cosottini, M, De Stefano, N, Pracucci, G, Pantoni, L, Inzitari, D, Diciotti, S, VMCI Tuscany Investigators: Inzitari, D, Abbate, R, Bandinelli, M, Boddi, M, Cesari, F, Ciolli, L, Coppo, M, Del Bene, A, Giusti, B, Gori, Am, Nannucci, S, Pasi, M, Pescini, F, Valenti, R, Bonucelli, U, Chiti, A, Orlandi, G, Pagni, C, Siciliano, G, Tognoni, G, Federico, A, Dotti, Mt, Formichi, P, Gambetti, C, Giorgio, A, Rossi, F, Stromillo, L, Zicari, E, Zolo, P, Tiezzi, A, Bertini, E, Brotini, S, Guidi, L, Lombardi, M, Mugnai, S, Notarelli, A, Bracco, L, Cadelo, M, Cisbani, R, Gabbani, L, Gori, G, Lambertucci, L, Massacesi, L, Mossello, E, Paganini, M, Piccininni, M, Pinto, F, Pozzi, C, Sorbi, S, Zaccara, G, Borgogni, T, Mancuso, M, Marconi, R, Mazzoni, M, Vista, M, Meucci, G, Bellini, G, Gabrielli, L, Frittelli, C, Galli, R, Gambaccini, G, Bartolini, S, Biagini, C, Caleri, V, Vanni, P, Calvani, D, Giorgi, C, Magnolfi, S, Palumbo, P, Valente, C, Rossi, A, Tassi, R, Boschi, S, and Baldacci, Filippo

Published
2014

36. MCI conversion to dementia and the Apoe genotype: a prediction study with FDG-PET

Author

Mosconi, L., Perani, D., Sorbi, S., Herholz, K., Nacmias, B., Holthoff, V., Salmon, E., jean-claude baron, Cristofaro, M. T. R., Padovani, A., Borroni, B., Franceschi, M., Bracco, L., Pupi, A., Mosconi, L, Perani, DANIELA FELICITA L., Sorbi, S, Herholz, K, Nacmias, B, Holthoff, V, Salmon, E, Baron, Jc, De Cristofaro, Mtr, Padovani, A, Borroni, B, Franceschi, M, Bracco, L, and Pupi, A.

Subjects
APOE genotype, FDG-PET, MCI
Published
2004

38. How legislation on decisional capacity can negatively affect the feasibility of clinical trials in patients with dementia

Author

Galeotti, F, Vanacore, N, Gainotti, S, Izzicupo, F, Menniti Ippolito, F, Petrini, C, Chiarotti, F, Chattat, R, Raschetti, R, AdCare Study Group: Popoli, P, Potenza, R, Tebano, Mt, Giubilei, F, Locuratolo, N, Bruno, G, Piacentini, E, Talarico, G, Gasparini, M, Del Re ML, Bruni, A, Colao, R, Puccio, G, Curcio, S, Clodimiro, A, Caffarra, P, Messa, G, Concari, L, Pagliara, B, Fabbo, A, Zucchi, P, Bonora, A, Veschi, M, Carbone, G, Ursino, R, Fatica, L, De Bonis, C, Gainotti, G, Marra, C, Quaranta, D, Zinno, M, Rodriguez, Guido, Nobili, FLAVIO MARIANO, Barbieri, Mp, Dessi, B, Mazzei, D, Arnaldi, Dario, Brugnolo, Andrea, Clerici, F, Mariani, C, Maggiore, L, Pomati, S, Padovani, A, Rozzini, L, Zanetti, M, Conti, M, Chinaglia, C, Engaddi, I, De Domenico, D, Savorgnan, G, Scarpino, O, Civerchia, P, Raccichini, A, Specchio, Lm, Goffredo, R, Biancardi, Me, Putzu, V, Araujo, Y, Ballisai, A, Piras, Mr, Cherchi, R, Bagella, Cf, Deiana, E, Giordano, M, Pineo, A, Catania, Tm, Bracco, L, Piccini, C, Mecocci, P, Feliziani, Ft, Cornacchiola, V, Gambina, G, Broggio, E, Sala, F., Galeotti F, Vanacore N, Gainotti S, Izzicupo F, Menniti-Ippolito F, Petrini C, Chiarotti F, Chattat R, Raschetti R, and AdCare Study Group

Subjects
Olanzapine, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Decision Making, Atypical antipsychotic, law.invention, Randomized controlled trial, Informed consent, law, Humans, Medicine, Mental Competency, Pharmacology (medical), Antipsychotic, Psychiatry, legal, Clinical Trials as Topic, Risperidone, business.industry, Patient Selection, CAPACITY, BPSD, antipsychotic, Clinical trial, Settore MED/26 - NEUROLOGIA, Feasibility Studies, Quetiapine, Dementia, Geriatrics and Gerontology, business, medicine.drug
Abstract

Antipsychotic drugs are widely used to treat behavioural and psychological disturbances associated with Alzheimer's disease (AD), although only modest evidence from randomized controlled trials supports their efficacy, and increasing evidence from post-marketing surveillance shows serious adverse events associated with their use, including increased mortality. The AdCare study, a non-profit, randomized, placebo-controlled, double-blind, multicentre, pragmatic trial coordinated by the Italian National Institute of Health, aimed to evaluate the long-term safety and efficacy profiles of three atypical antipsychotic drugs (risperidone, olanzapine and quetiapine) and one conventional antipsychotic drug (haloperidol) in treating psychosis, aggression and agitation in outpatients with AD. The study was planned to be carried out in 19 clinical centres and to enrol 1000 outpatients. According to Italian law, in the case where a patient is considered unable to give informed consent, a legal representative designated by the court has to provide it. Because of difficulties in the informed consent procedure, the study had to be prematurely interrupted. From February 2009 to April 2010, 83 patients gave informed consent to participate in the trial. Fifty-six patients (68%) were included with consent given by a legal representative, while 27 patients (32%) were considered to provide personal informed consent on the basis of the results from a specifically built procedure. Patients and caregivers were offered the opportunity to participate in the trial before the occurrence of behavioural disturbances, in order to provide them with enough time to consider their participation in the study. Twenty-three patients experienced behavioural, clinically relevant symptoms and were randomized to the study drug; all randomized patients except one had consent for inclusion in the study given by legal representatives. After trial interruption, all patients taking an active drug continued treatment with the same molecule in clinical practice. Randomized controlled trials are acknowledged as the gold standard source of evidence on drug safety and efficacy. The AdCare study showed that an excessively rigid regulation can become a major obstacle while carrying out therapeutic research with incapacitated persons.

Published
2012

40. AD: role of clinical examinations in predicting neurpathological features

Author

Campani D, Marcon G, Bracco L, Simonati A, Rizzuto N, Piccininni M, Piccini D, Manfredi G, Falcini M, Notarelli A, Amaducci L, Campani, D, Marcon, G, Bracco, L, Simonati, A, Rizzuto, N, Piccininni, M, Piccini, D, Manfredi, G, Falcini, M, Notarelli, A, and Amaducci, L

Published
1995

42. FACTORS AFFECTING COURSE AND SURVIVAL IN ALZHEIMERS-DISEASE - A 9-YEAR LONGITUDINAL-STUDY

Author

Bracco, L, Gallato, R, Grigoletto, F, Lippi, A, Lepore, V, Bino, G, Lazzaro, Mp, Carella, F, Piccolo, T, Pozzilli, C, Giometto, B, Amaducci, L, Bracco, L, Gallato, R, Grigoletto, F, Lippi, A, Lepore, V, Bino, G, Lazzaro, Mp, Carella, F, Piccolo, T, Pozzilli, C, Giometto, B, and Amaducci, L

Abstract

Objective: To evaluate mean survival and to identify prognostic factors in a cohort of patients with Alzheimer's disease (AD). Design: Multicentric 9-year cohort analytic study. Setting: Seven neurology departments throughout Italy between April 1982 and January 1984. Patients: We recruited a consecutive sample of 145 patients affected by probable AD (Multicenter Italian Study on Dementia protocol, National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria). Five were misdiagnosed, and 21 could not participate in the longitudinal study. The clinicodemographic characteristics of the 119 enrolled patients (49 men, 70 women; mean age, 64.7 years; SD, 4.1 years; mean duration of disease, 3.1 years; SD, 1.8 years) did not differ from those of the 26 excluded patients. All underwent extensive cliniconeuropsychological testing every 6 months for at least 2 years until the patient died or our survey ended (April 30, 1991). Mean follow-up was 5.1 years (SD, 2.5 years). Main Outcome Measures: Death, severe functional impairment (a score greater than or equal to 7 on the Blessed Dementia Scale),and severe cognitive impairment (a score of less than or equal to 7 on the Information-Memory-Concentration Test). Results: Survival curves obtained by the Kaplan-Meier method indicated that (1) patients with early- and late-onset disease tie, before or after age 65 years) showed no difference either in relative survival or in time to reach predetermined functional and cognitive end points; (2) severely aphasic patients became profoundly demented significantly sooner than those with mild to moderate aphasia (P

Published
1994

43. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET

Author

Mosconi L. 1, 7, Perani D. 3, 4, Sorbi S. 2, Herholz K., 8, Nacmias B. 2, Holthoff V. 10, Salmon E. 11, Baron J.C. 9, De Cristofaro M.T. 1, Padovani A. 5, Borroni B. 6, 9, Franceschi M. 5, Bracco L. 2, and Pupi A. 1

Subjects
PET, AD, MCI, APOE
Abstract

OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.

Published
2004

48. SURVIVAL IN SENILE AND PRESENILE ALZHEIMERS-DISEASE

Author

BRACCO L, LIPPI A, AMADUCCI L, GALLATO R, GRIGOLETTO F, TERME A, PEDONE D, LIVREA P, BINO G, TABATON M, MORETTI C, LOEB C, BONATTI ML, CAMPANOZZI F, PRENCIPE M, PICCOLO T, CARACENI T, GIOMETTO B, TAVOLATO B, BATTISTIN L, DANTONA R, FIESCHI C, Bracco, L, Lippi, A, Amaducci, L, Gallato, R, Grigoletto, F, Terme, A, Pedone, D, Livrea, P, Bino, G, Tabaton, M, Moretti, C, Loeb, C, Bonatti, Ml, Campanozzi, F, Prencipe, M, Piccolo, T, Caraceni, T, Giometto, B, Tavolato, B, Battistin, L, Dantona, R, and Fieschi, C

Published
1990

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