Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study
Stephanie J.B. Vos,Chengjie Xiong,Pieter Jelle Visser,Pieter Jelle Visser,Mateusz S. Jasielec,Jason Hassenstab,Elizabeth A. Grant,Nigel J. Cairns,John C. Morris,David M. Holtzman,Anne M. Fagan +10 more
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TLDR
Compared with individuals classed as normal, participants with preclinical Alzheimer's disease had an increased risk of death after adjusting for covariates, and could be an important target for therapeutic intervention.Abstract:
Summary Background New research criteria for preclinical Alzheimer's disease have been proposed, which include stages for cognitively normal individuals with abnormal amyloid markers (stage 1), abnormal amyloid and neuronal injury markers (stage 2), or abnormal amyloid and neuronal injury markers and subtle cognitive changes (stage 3). We aimed to investigate the prevalence and long-term outcome of preclinical Alzheimer's disease according to these criteria. Methods Participants were cognitively normal (clinical dementia rating [CDR]=0) community-dwelling volunteers aged at least 65 years who were enrolled between 1998 and 2011 at the Washington University School of Medicine (MO, USA). CSF amyloid-β 1–42 and tau concentrations and a memory composite score were used to classify participants as normal (both markers normal), preclinical Alzheimer's disease stage 1–3, or suspected non-Alzheimer pathophysiology (SNAP, abnormal injury marker without abnormal amyloid marker). The primary outcome was the proportion of participants in each preclinical AD stage. Secondary outcomes included progression to CDR at least 0·5, symptomatic Alzheimer's disease (score of at least 0·5 for memory and at least one other domain and cognitive impairments deemed to be due to Alzheimer's disease), and mortality. We undertook survival analyses using subdistribution and standard Cox hazards models and linear mixed models. Findings Of 311 participants, 129 (41%) were classed as normal, 47 (15%) as stage 1, 36 (12%) as stage 2, 13 (4%) as stage 3, 72 (23%) as SNAP, and 14 (5%) remained unclassified. The 5-year progression rate to CDR at least 0·5, symptomatic Alzheimer's disease was 2% for participants classed as normal, 11% for stage 1, 26% for stage 2, 56% for stage 3, and 5% for SNAP. Compared with individuals classed as normal, participants with preclinical Alzheimer's disease had an increased risk of death after adjusting for covariates (hazard ratio 6·2, 95% CI 1·1–35·0; p=0·040). Interpretation Preclinical Alzheimer's disease is common in cognitively normal elderly people and is associated with future cognitive decline and mortality. Thus, preclinical Alzheimer's disease could be an important target for therapeutic intervention. Funding National Institute of Aging of the National Institutes of Health (P01-AG003991, P50-AG05681, P01-AG02676), Internationale Stichting Alzheimer Onderzoek, the Center for Translational Molecular Medicine project LeARN, the EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and the Charles and Joanne Knight Alzheimer Research Initiative.read more
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NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.
Justin M. Long,David M. Holtzman +1 more
TL;DR: Recent advances in the understanding of AD pathobiology are reviewed and current treatment strategies are discussed, highlighting recent clinical trials and opportunities for developing future disease-modifying therapies.
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Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.
Bruno Dubois,Harald Hampel,Harald Hampel,Howard Feldman,Philip Scheltens,Paul S. Aisen,Sandrine Andrieu,Hovagim Bakardjian,Habib Benali,Lars Bertram,Lars Bertram,Kaj Blennow,Karl Broich,Enrica Cavedo,Sebastian J. Crutch,Jean-François Dartigues,Charles Duyckaerts,Stéphane Epelbaum,Giovanni B. Frisoni,Serge Gauthier,Remy Genthon,Alida A. Gouw,Alida A. Gouw,Marie-Odile Habert,David M. Holtzman,Miia Kivipelto,Miia Kivipelto,Simone Lista,José Luis Molinuevo,Sid E. O'Bryant,Gil D. Rabinovici,Christopher C. Rowe,Stephen Salloway,Lon S. Schneider,Reisa A. Sperling,Reisa A. Sperling,Marc Teichmann,Maria C. Carrillo,Jeffrey L. Cummings,Cliff R. Jack +39 more
TL;DR: An updated review of the literature and evidence on the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage of Alzheimer's disease are provided.
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Defeating Alzheimer's disease and other dementias: a priority for European science and society
Bengt Winblad,Bengt Winblad,Philippe Amouyel,Sandrine Andrieu,Clive Ballard,Carol Brayne,Henry Brodaty,Angel Cedazo-Minguez,Bruno Dubois,David Edvardsson,David Edvardsson,Howard Feldman,Laura Fratiglioni,Giovanni B. Frisoni,Serge Gauthier,Jean Georges,Caroline Graff,Caroline Graff,Khalid Iqbal,Frank Jessen,Frank Jessen,Gunilla Johansson,Linus Jönsson,Miia Kivipelto,Miia Kivipelto,Martin Knapp,Francesca Mangialasche,René J. F. Melis,Agneta Nordberg,Agneta Nordberg,Marcel G. M. Olde Rikkert,Chengxuan Qiu,Thomas P. Sakmar,Thomas P. Sakmar,Philip Scheltens,Lon S. Schneider,Reisa A. Sperling,Lars O. Tjernberg,Gunhild Waldemar,Anders Wimo,Henrik Zetterberg,Henrik Zetterberg +41 more
TL;DR: This poster aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the physical and cognitive properties of Alzheimer's disease and other dementias.
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
Willemijn J. Jansen,Rik Ossenkoppele,Dirk L. Knol,Betty M. Tijms,Philip Scheltens,Frans R.J. Verhey,Pieter Jelle Visser +6 more
TL;DR: Among persons without dementia, the prevalence of cerebral amyloid pathology as determined by positron emission tomography or cerebrospinal fluid findings was associated with age, apolipoprotein E [APOE] genotype, sex, and education, and presence of cognitive impairment.
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