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Find video protocols related to scientific articles indexed in Pubmed.
Classifying neurocognitive disorders: the DSM-5 approach.
Nat Rev Neurol
PUBLISHED: 09-30-2014
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Neurocognitive disorders-including delirium, mild cognitive impairment and dementia-are characterized by decline from a previously attained level of cognitive functioning. These disorders have diverse clinical characteristics and aetiologies, with Alzheimer disease, cerebrovascular disease, Lewy body disease, frontotemporal degeneration, traumatic brain injury, infections, and alcohol abuse representing common causes. This diversity is reflected by the variety of approaches to classifying these disorders, with separate groups determining criteria for each disorder on the basis of aetiology. As a result, there is now an array of terms to describe cognitive syndromes, various definitions for the same syndrome, and often multiple criteria to determine a specific aetiology. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides a common framework for the diagnosis of neurocognitive disorders, first by describing the main cognitive syndromes, and then defining criteria to delineate specific aetiological subtypes of mild and major neurocognitive disorders. The DSM-5 approach builds on the expectation that clinicians and research groups will welcome a common language to deal with the neurocognitive disorders. As the use of these criteria becomes more widespread, a common international classification for these disorders could emerge for the first time, thus promoting efficient communication among clinicians and researchers.
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The explanatory role of stroke as a mediator of the mortality risk difference between older adults who initiate first- versus second-generation antipsychotic drugs.
Am. J. Epidemiol.
PUBLISHED: 09-18-2014
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Antipsychotic drugs are used to treat dementia-related symptoms in older adults, and observational studies show higher risks of death and stroke associated with the use of first-generation antipsychotic drugs (FGAs) compared with second-generation antipsychotic drugs (SGAs). However, the extent to which stroke explains the differential mortality risk between FGA use and SGA use in older adults is unclear. We followed those who initiated use of antipsychotic drugs (9,777 FGA users and 21,164 SGA users) aged 65 years or older, and who were enrolled in Medicare and either the New Jersey or Pennsylvania pharmacy assistance program during 1994 to 2005, over 180 days for the outcomes of stroke and death. We estimated direct and indirect effects by comparing 180-day mortality risks associated with the use of FGAs versus SGAs as mediated by stroke on the risk ratio scale, as well as the proportion mediated on the risk difference scale. FGA use was associated with marginally higher risks of stroke (risk ratio =1.24, 95% confidence interval (CI): 1.01, 1.53) and death (risk ratio = 1.15, 95% CI: 1.08, 1.22) compared with SGA use, but stroke explained little (2.7%) of the observed difference in mortality risk. The indirect effect was null (risk ratio = 1.004, 95% CI: 1.000, 1.008), and the direct effect was equal to the total effect of antipsychotic drug type (FGA vs. SGA) on mortality risk (risk ratio = 1.15, 95% CI: 1.08, 1.22). These results suggest that the difference in mortality risk between users of FGAs and SGAs may develop mostly through pathways that do not involve stroke.
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Effects of multiple genetic Loci on age at onset in late-onset Alzheimer disease: a genome-wide association study.
Adam C Naj, Gyungah Jun, Christiane Reitz, Brian W Kunkle, William Perry, Yo Son Park, Gary W Beecham, Ruchita A Rajbhandary, Kara L Hamilton-Nelson, Li-San Wang, John S K Kauwe, Matthew J Huentelman, Amanda J Myers, Thomas D Bird, Bradley F Boeve, Clinton T Baldwin, Gail P Jarvik, Paul K Crane, Ekaterina Rogaeva, M Michael Barmada, F Yesim Demirci, Carlos Cruchaga, Patricia L Kramer, Nilüfer Ertekin-Taner, John Hardy, Neill R Graff-Radford, Robert C Green, Eric B Larson, Peter H St George-Hyslop, Joseph D Buxbaum, Denis A Evans, Julie A Schneider, Kathryn L Lunetta, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, Philip L De Jager, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Eden R Martin, Jonathan L Haines, Richard P Mayeux, Lindsay A Farrer, Gerard D Schellenberg, Margaret A Pericak-Vance, , Marilyn S Albert, Roger L Albin, Liana G Apostolova, Steven E Arnold, Robert Barber, Lisa L Barnes, Thomas G Beach, James T Becker, Duane Beekly, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Chris S Carlson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Helena C Chui, David G Clark, Jason Corneveaux, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Steven T DeKosky, Malcolm Dick, Dennis W Dickson, Ranjan Duara, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, Joel H Kramer, Frank M Laferla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Chiao-Feng Lin, Oscar L Lopez, Constantine G Lyketsos, Wendy J Mack, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Jill R Murrell, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Howard J Rosen, Roger N Rosenberg, Mary Sano, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Otto Valladares, Vivianna M Van Deerlin, Linda J Van Eldik, Badri N Vardarajan, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L Woltjer, Clinton B Wright, Steven G Younkin, Chang-En Yu, Lei Yu.
JAMA Neurol
PUBLISHED: 09-10-2014
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Because APOE locus variants contribute to risk of late-onset Alzheimer disease (LOAD) and to differences in age at onset (AAO), it is important to know whether other established LOAD risk loci also affect AAO in affected participants.
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Quantifying the role of adverse events in the mortality difference between first and second-generation antipsychotics in older adults: systematic review and meta-synthesis.
PLoS ONE
PUBLISHED: 08-20-2014
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Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.
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A new algorithm for predicting time to disease endpoints in Alzheimer's disease patients.
J. Alzheimers Dis.
PUBLISHED: 07-18-2014
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The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies.
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SIST-M-IR activities of daily living items that best discriminate clinically normal elderly from those with mild cognitive impairment.
Curr Alzheimer Res
PUBLISHED: 04-04-2014
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Activities of daily living (ADL) impairment is a hallmark of Alzheimer's disease (AD) dementia, but impairment in instrumental ADL (IADL) has been reported in mild cognitive impairment (MCI). The Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center (MADRC)-Informant Report (SIST-MIR) includes 60 graded items that assist in scoring the Clinical Dementia Rating; it assesses the spectrum of cognitive and ADL changes relevant to early AD. Of the 60 SIST-M-IR items, 41 address IADL; we aimed to determine which of these best discriminate individuals with MCI from clinically normal (CN) elderly.
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Social cognition in Alzheimer's disease: A separate construct contributing to dependence.
Alzheimers Dement
PUBLISHED: 03-25-2014
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The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability.
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Health-care use and cost in dementia caregivers: Longitudinal results from the Predictors Caregiver Study.
Alzheimers Dement
PUBLISHED: 03-19-2014
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To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost.
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Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.
Alzheimer Dis Assoc Disord
PUBLISHED: 03-18-2014
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Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination.
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Early and late menarche and risk of depressive symptoms in young adulthood.
Arch Womens Ment Health
PUBLISHED: 02-28-2014
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We investigated whether girls experiencing early menarche have an increased risk of depression during young adulthood. This study used data collected in the Growing Up Today Study (N?=?9,039), an ongoing prospective cohort of the daughters of women enrolled in the Nurses' Health Study II. After excluding girls who were postmenarcheal at baseline in 1996, <20 or ?26 years old in 2007, or missing data on key covariates, the final sample size was 3,711. Self-reported age at menarche was collected annually. Depressive symptomatology was measured in 2007 using the 10-item Center for Epidemiologic Studies Depression (CES-D-10) score. Sixteen percent of girls (N?=?596) reported high levels of depressive symptoms (CES-D-10???14) in 2007. Neither early nor late menarche was associated with high depressive symptoms (for early vs. normative menarche, odds ratio (OR)?=?1.08, 95 % confidence interval (CI)?=?0.85-1.38; for late vs. normative menarche, OR?=?0.91, 95 % CI?=?0.70-1.18) or with differences in continuous CES-D-10 score in young adulthood. Although previous studies suggest that girls with early menarche suffer from an increased risk of adolescent depression, this does not appear to persist into young adulthood.
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Mild to moderate Alzheimer dementia with insufficient neuropathological changes.
Ann. Neurol.
PUBLISHED: 01-22-2014
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Recently, ~16% of participants in an anti-A? passive immunotherapy trial for mild-to-moderate Alzheimer disease (AD) had a negative baseline amyloid positron emission tomography (PET) scan. Whether they have AD or are AD clinical phenocopies remains unknown. We examined the 2005-2013 National Alzheimer's Coordinating Center autopsy database and found that ~14% of autopsied subjects clinically diagnosed with mild-to-moderate probable AD have no or sparse neuritic plaques, which would expectedly yield a negative amyloid PET scan. More than half of these "A?-negative" subjects have low neurofibrillary tangle Braak stages. These findings support the implementation of a positive amyloid biomarker as an inclusion criterion in future anti-A? drug trials.
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Subjective Cognitive Concerns and Neuropsychiatric Predictors of Progression to the Early Clinical Stages of Alzheimer Disease.
Am J Geriatr Psychiatry
PUBLISHED: 01-06-2014
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To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD).
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Valentina Escott-Price, Celine Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L Destefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, , Andrew D Johnson, Agustin Ruíz, Marie-Therese Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimón, Alberto Lleó, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renée F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-Francois Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramírez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams.
PLoS ONE
PUBLISHED: 01-01-2014
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Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
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Postmenopausal hormone therapy is not associated with risk of all-cause dementia and Alzheimers disease.
Epidemiol Rev
PUBLISHED: 09-15-2013
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The relationship of postmenopausal hormone therapy with all-cause dementia and Alzheimers disease dementia has been controversial. Given continued interest in the role of hormone therapy in chronic disease prevention and the emergence of more prospective studies, we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on postmenopausal hormone therapy use and risk of Alzheimers disease or dementia. A systematic search of Medline and Embase through December 31, 2012, returned 15 articles meeting our criteria. Our meta-analysis of any versus never use did not support the hypothesis that hormone therapy reduces risk of Alzheimers disease (summary estimate = 0.88, 95% confidence interval: 0.66, 1.16). Exclusion of trial findings did not change this estimate. There were not enough all-cause dementia results for a separate meta-analysis, but when we combined all-cause dementia results (n = 3) with Alzheimers disease results (n = 7), the summary estimate remained null (summary estimate = 0.94, 95% confidence interval: 0.71, 1.26). The limited explorations of timing of use-both duration and early initiation-did not yield consistent findings. Our findings support current recommendations that hormone therapy should not be used for dementia prevention. We discuss trends in hormone therapy research that could explain our novel findings and highlight areas where additional data are needed.
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Challenges in assessing depressive symptoms in Fiji: A psychometric evaluation of the CES-D.
Int J Soc Psychiatry
PUBLISHED: 07-22-2013
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and AIM: The CES-D is a commonly used self-report assessment for depressive symptomatology. However, its psychometric properties have not been evaluated in Fiji. This study aims to evaluate the reliability and validity of English language and Fijian vernacular versions in ethnic Fijian adolescent schoolgirls.
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Properties of permutation-based gene tests and controlling type 1 error using a summary statistic based gene test.
BMC Genet.
PUBLISHED: 06-11-2013
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The advent of genome-wide association studies has led to many novel disease-SNP associations, opening the door to focused study on their biological underpinnings. Because of the importance of analyzing these associations, numerous statistical methods have been devoted to them. However, fewer methods have attempted to associate entire genes or genomic regions with outcomes, which is potentially more useful knowledge from a biological perspective and those methods currently implemented are often permutation-based.
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Principal components methods for narrow-sense heritability in the analysis of multidimensional longitudinal cognitive phenotypes.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 02-06-2013
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Genetic association studies of longitudinal cognitive phenotypes are an alternate approach to discovering genetic risk factors for Alzheimers disease (AD). However, the standard linear mixed model approach is limited in the face of multidimensional longitudinal data and multiple genotypes. In this setting, the principal components of heritability (PCH) approach may increase efficiency by deriving a linear combination of phenotypes to maximize the heritability attributable to a particular genetic locus. The current study investigated the performance of two PCH methods, the Principal Components of Heritability Association Test (PCHAT) and C2BAT, in detecting association of the known AD susceptibility allele APOE-?4 with cognitive function at baseline and decline in cognition over time.
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Utilization of antihypertensives, antidepressants, antipsychotics, and hormones in Alzheimer disease.
Alzheimer Dis Assoc Disord
PUBLISHED: 10-20-2011
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This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.
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The association between blood pressure and incident Alzheimer disease: a systematic review and meta-analysis.
Epidemiology
PUBLISHED: 06-28-2011
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Many epidemiologic studies have considered the association between blood pressure (BP) and Alzheimer disease, yet the relationship remains poorly understood.
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Failure of repetition suppression and memory encoding in aging and Alzheimers disease.
Brain Imaging Behav
PUBLISHED: 04-26-2011
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The suppression of neural activity in the medial temporal lobe (MTL) has been suggested as a marker of successful recognition of familiarity in healthy subjects, but to be impaired in patients with Alzheimers disease (AD). In this study, we investigated whether the ability to suppress MTL activity during repeated exposure to face-name pairs was related to the ability to successfully encode novel associations in 90 individuals ranging from healthy young and older subjects to mildly impaired elderly and AD patients. Activity in the anterior MTL during Repeated stimuli was inversely related to performance in post-scan associative recognition for the Novel face-name pairs. In a subset (n=60) of subjects undergoing more detailed neuropsychological testing, greater MTL Repeated activity was correlated with worse word-list delayed recall performance. Failure of response suppression to familiar information may be a sensitive marker of MTL dysfunction and memory impairment in aging and prodromal AD.
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The Structured Interview & Scoring Tool-Massachusetts Alzheimers Disease Research Center (SIST-M): development, reliability, and cross-sectional validation of a brief structured clinical dementia rating interview.
Arch. Neurol.
PUBLISHED: 03-16-2011
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The Clinical Dementia Rating (CDR) and CDR Sum-of-Boxes can be used to grade mild but clinically important cognitive symptoms of Alzheimer disease. However, sensitive clinical interview formats are lengthy.
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Genome scan of age-at-onset in the NIMH Alzheimer disease sample uncovers multiple loci, along with evidence of both genetic and sample heterogeneity.
Am. J. Med. Genet. B Neuropsychiatr. Genet.
PUBLISHED: 03-14-2011
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Alzheimers disease (AD) is a common neurodegenerative disorder of late life with a complex genetic basis. Although several genes are known to play a role in rare early onset AD, only the APOE gene is known to have a high contribution to risk of the common late-onset form of the disease (LOAD, onset >60 years). APOE genotypes vary in their AD risk as well as age-at-onset distributions, and it is likely that other loci will similarly affect AD age-at-onset. Here we present the first analysis of age-at-onset in the NIMH LOAD sample that allows for both a multilocus trait model and genetic heterogeneity among the contributing sites, while at the same time accommodating age censoring, effects of known genetic covariates, and full pedigree and marker information. The results provide evidence for genomic regions not previously implicated in this data set, including regions on chromosomes 7q, 15, and 19p. They also affirm evidence for loci on chromosomes 1q, 6p, 9q, 11, and, of course, the APOE locus on 19q, all of which have been reported previously in the same sample. The analyses failed to find evidence for linkage to chromosome 10 with inclusion of unaffected subjects and extended pedigrees. Several regions implicated in these analyses in the NIMH sample have been previously reported in genome scans of other AD samples. These results, therefore, provide independent confirmation of AD loci in family-based samples on chromosomes 1q, 7q, 19p, and suggest that further efforts towards identifying the underlying causal loci are warranted.
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Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimers disease.
Adam C Naj, Gyungah Jun, Gary W Beecham, Li-San Wang, Badri Narayan Vardarajan, Jacqueline Buros, Paul J Gallins, Joseph D Buxbaum, Gail P Jarvik, Paul K Crane, Eric B Larson, Thomas D Bird, Bradley F Boeve, Neill R Graff-Radford, Philip L De Jager, Denis Evans, Julie A Schneider, Minerva M Carrasquillo, Nilüfer Ertekin-Taner, Steven G Younkin, Carlos Cruchaga, John S K Kauwe, Petra Nowotny, Patricia Kramer, John Hardy, Matthew J Huentelman, Amanda J Myers, Michael M Barmada, F Yesim Demirci, Clinton T Baldwin, Robert C Green, Ekaterina Rogaeva, Peter St George-Hyslop, Steven E Arnold, Robert Barber, Thomas Beach, Eileen H Bigio, James D Bowen, Adam Boxer, James R Burke, Nigel J Cairns, Chris S Carlson, Regina M Carney, Steven L Carroll, Helena C Chui, David G Clark, Jason Corneveaux, Carl W Cotman, Jeffrey L Cummings, Charles DeCarli, Steven T DeKosky, Ramon Diaz-Arrastia, Malcolm Dick, Dennis W Dickson, William G Ellis, Kelley M Faber, Kenneth B Fallon, Martin R Farlow, Steven Ferris, Matthew P Frosch, Douglas R Galasko, Mary Ganguli, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Sid Gilman, Bruno Giordani, Jonathan D Glass, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Elizabeth Head, Lawrence S Honig, Christine M Hulette, Bradley T Hyman, Gregory A Jicha, Lee-Way Jin, Nancy Johnson, Jason Karlawish, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Edward H Koo, Neil W Kowall, James J Lah, Allan I Levey, Andrew P Lieberman, Oscar L Lopez, Wendy J Mack, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Joseph E Parisi, Daniel P Perl, Elaine Peskind, Ronald C Petersen, Wayne W Poon, Joseph F Quinn, Ruchita A Rajbhandary, Murray Raskind, Barry Reisberg, John M Ringman, Erik D Roberson, Roger N Rosenberg, Mary Sano, Lon S Schneider, William Seeley, Michael L Shelanski, Michael A Slifer, Charles D Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Rudolph E Tanzi, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Jennifer Williamson, Randall L Woltjer, Laura B Cantwell, Beth A Dombroski, Duane Beekly, Kathryn L Lunetta, Eden R Martin, M Ilyas Kamboh, Andrew J Saykin, Eric M Reiman, David A Bennett, John C Morris, Thomas J Montine, Alison M Goate, Deborah Blacker, Debby W Tsuang, Hakon Hakonarson, Walter A Kukull, Tatiana M Foroud, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Lindsay A Farrer, Gerard D Schellenberg.
Nat. Genet.
PUBLISHED: 03-10-2011
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The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimers disease susceptibility.
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Clinical impact of updated diagnostic and research criteria for Alzheimers disease.
J Clin Psychiatry
PUBLISHED: 01-11-2011
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Almost 30 years ago, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimers Disease and Related Disorders Association (more commonly known as the Alzheimers Association) developed the original clinical diagnostic criteria for Alzheimers disease (AD). Recently, the National Institute on Aging and the Alzheimers Association released updated research and diagnostic criteria for AD. The new criteria establish that AD exists on a continuum and is comprised of not only dementia but also a preclinical phase and a phase of mild cognitive impairment due to AD. The new criteria also describe advancements in biomarker evidence, which is still being researched and is not yet ready for clinical settings. Additionally, the American Psychiatric Association is currently revising the Diagnostic and Statistical Manual of Mental Disorders, which will include updated diagnostic criteria for AD and other neurocognitive disorders.
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Longitudinal medication usage in Alzheimer disease patients.
Alzheimer Dis Assoc Disord
PUBLISHED: 07-14-2010
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This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n=201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patients living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients.
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The cortical signature of Alzheimers disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals.
Cereb. Cortex
PUBLISHED: 12-18-2009
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Alzheimers disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This "disease signature" approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases.
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Comparison of patient and caregiver reports of patient activity participation and its relationship to mental health in patients with Alzheimers disease.
J Gerontol B Psychol Sci Soc Sci
PUBLISHED: 10-05-2009
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The relationship between engagement in pleasant activities as rated by the patient and as rated by the caregiver from the patients perspective was examined using structural equation modeling in a sample of patients (N = 277) diagnosed with mild to moderate Alzheimers disease. The two activity participation ratings were only moderately related to one another. Furthermore, depression was the only significant predictor of the patient-rated activity participation, whereas severity of depression, degree of personality change, level of dependence, and cognition were all significant predictors of caregiver-rated activity participation. These findings suggest that caregivers consider a wider range of variables when evaluating the patients engagement in activities than does the patient. Predictors of patient-rated activity participation did not differ as a function of age or cognition.
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Seizures in Alzheimer disease: who, when, and how common?
Arch. Neurol.
PUBLISHED: 08-12-2009
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Transient symptoms in Alzheimer disease (AD) are frequent and include seizures, syncope, and episodes of inattention or confusion. The incidence of seizures in AD and predictors of which patients with AD might be more predisposed to them is based primarily on retrospective studies and is not well established.
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Assessment of Alzheimers disease case-control associations using family-based methods.
Neurogenetics
PUBLISHED: 07-14-2009
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The genetics of Alzheimers disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org ) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case-control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes.
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GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results.
Arch. Neurol.
PUBLISHED: 02-11-2009
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Genomewide association (GWA) studies have recently implicated 4 novel Alzheimer disease (AD) susceptibility loci (GAB2, GOLM1, and 2 uncharacterized loci to date on chromosomes 9p and 15q). To our knowledge, these findings have not been independently replicated.
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MRI-derived measurements of human subcortical, ventricular and intracranial brain volumes: Reliability effects of scan sessions, acquisition sequences, data analyses, scanner upgrade, scanner vendors and field strengths.
Neuroimage
PUBLISHED: 01-22-2009
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Automated MRI-derived measurements of in-vivo human brain volumes provide novel insights into normal and abnormal neuroanatomy, but little is known about measurement reliability. Here we assess the impact of image acquisition variables (scan session, MRI sequence, scanner upgrade, vendor and field strengths), FreeSurfer segmentation pre-processing variables (image averaging, B1 field inhomogeneity correction) and segmentation analysis variables (probabilistic atlas) on resultant image segmentation volumes from older (n=15, mean age 69.5) and younger (both n=5, mean ages 34 and 36.5) healthy subjects. The variability between hippocampal, thalamic, caudate, putamen, lateral ventricular and total intracranial volume measures across sessions on the same scanner on different days is less than 4.3% for the older group and less than 2.3% for the younger group. Within-scanner measurements are remarkably reliable across scan sessions, being minimally affected by averaging of multiple acquisitions, B1 correction, acquisition sequence (MPRAGE vs. multi-echo-FLASH), major scanner upgrades (Sonata-Avanto, Trio-TrioTIM), and segmentation atlas (MPRAGE or multi-echo-FLASH). Volume measurements across platforms (Siemens Sonata vs. GE Signa) and field strengths (1.5 T vs. 3 T) result in a volume difference bias but with a comparable variance as that measured within-scanner, implying that multi-site studies may not necessarily require a much larger sample to detect a specific effect. These results suggest that volumes derived from automated segmentation of T1-weighted structural images are reliable measures within the same scanner platform, even after upgrades; however, combining data across platform and across field-strength introduces a bias that should be considered in the design of multi-site studies, such as clinical drug trials. The results derived from the young groups (scanner upgrade effects and B1 inhomogeneity correction effects) should be considered as preliminary and in need for further validation with a larger dataset.
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The role of peripheral inflammatory markers in dementia and Alzheimers disease: a meta-analysis.
J. Gerontol. A Biol. Sci. Med. Sci.
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Studies that have investigated the association between markers of inflammation and risk of dementia are conflicting. Therefore, the researchers conducted a systematic review and meta-analysis of observational studies with the hypothesis that an increased level of peripheral proinflammatory markers would be associated with risk of all-cause dementia or Alzheimers disease (AD).
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Plasma amyloid-? as a predictor of dementia and cognitive decline: a systematic review and meta-analysis.
Arch. Neurol.
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Preclinical prediction of Alzheimer disease (AD) is important and critical to effective intervention. Plasma levels of amyloid-? (A?) peptides have been a principal focus of the growing literature on blood-based biomarkers, but studies to date have varied in design, assay methods, and sample size, making it difficult to readily interpret the overall data.
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Change in Body Mass Index Before and After Alzheimers Disease Onset.
Curr Alzheimer Res
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Objectives: A high body mass index (BMI) in middle-age or a decrease in BMI at late-age has been considered a predictor for the development of Alzheimers disease (AD). However, little is known about the BMI change close to or after AD onset. Methods: BMI of participants from three cohorts, the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based), and National Alzheimer's Coordinating Center (NACC; clinic-based) were analyzed longitudinally. We used generalized estimating equations to test whether there were significant changes of BMI over time, adjusting for age, sex, education, race, and research center. Stratification analyses were run to determine whether BMI changes depended on baseline BMI status. Results: BMI declined over time up to AD clinical onset, with an annual decrease of 0.21 (p=0.02) in WHICAP and 0.18 (p=0.04) kg/m2 in NACC. After clinical onset of AD, there was no significant decrease of BMI. BMI even increased (b=0.11, p=0.004) among prevalent AD participants in NACC. During the prodromal period, BMI decreased over time in overweight(BMI ?25 and <30) WHICAP participants or obese (BMI?30)NACC participants. After AD onset, BMI tended to increase in underweight/normal weight (BMI<25) patients and decrease in obese patients in all three cohorts, although the results were significant in NACC study only. Conclusions: Our study suggests that while BMI declines before the clinical AD onset, it levels off after clinical AD onset, and might even increase in prevalent AD. The pattern of BMI change may also depend on the initial BMI.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.