Journal ArticleDOI
Pathologic correlates of nondemented aging, mild cognitive impairment, and early-stage Alzheimer's disease.
John C. Morris,Joseph L. Price +1 more
TLDR
It is concluded that widespread amyloid plaques in the neocortex best distinguishes very early stage AD, including “MCI” stage, and preclinical stages, from healthy brain aging and it is now critical to develop methods to detect preclinical AD during life.Abstract:
The results of studies from the Washington University Alzheimer Disease (AD) Research Center and those from other centers and investigators regarding the neuropathologic correlates of normal aging and early-stage AD are reviewed. We conclude that widespread amyloid plaques in the neocortex best distinguishes very early stage AD, including “MCI” stage, and preclinical stages, from healthy brain aging. Other AD lesions, including increased formation of neurofibrillary tangles and neuronal degeneration appear to result from the amyloid-initiated pathologic process, although they may have a more immediate effect on expression and severity of dementia. These data provide strong support for anti-amyloid intervention as a preventive therapy for AD. It is now critical to develop methods to detect preclinical AD during life.read more
Citations
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Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.
William E. Klunk,Henry Engler,Agneta Nordberg,Yanming Wang,G. Blomqvist,Daniel P. Holt,Mats Bergström,Irina Savitcheva,Guo Feng Huang,Sergio Estrada,Birgitta Ausén,Manik L. Debnath,Julien Barletta,Julie C. Price,Johan Sandell,Brian J. Lopresti,Anders Wall,Pernilla Koivisto,Gunnar Antoni,Chester A. Mathis,Bengt Långström +20 more
TL;DR: The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.
Journal ArticleDOI
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.
Journal ArticleDOI
Alzheimer’s Disease: The Challenge of the Second Century
TL;DR: Current information suggests that if the disease is detected before the onset of overt symptoms, it is possible that treatments based on knowledge of underlying pathogenesis can and will be effective.
Journal ArticleDOI
Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans.
Anne M. Fagan,Mark A. Mintun,Robert H. Mach,Sang-Yoon Lee,Carmen S. Dence,Aarti R. Shah,Gina N. LaRossa,Michael L. Spinner,William E. Klunk,Chester A. Mathis,Steven T. DeKosky,John C. Morris,David M. Holtzman +12 more
TL;DR: Amyloid‐β42 (Aβ42) appears central to Alzheimer's disease pathogenesis and is a major component of amyloid plaques, and its decrease may reflect plaques acting as an Aβ42 “sink,” hindering transport of soluble A β42 between brain and CSF.
Book
Vascular Cognitive Impairment
John T. O'Brien,Timo Erkinjuntti,Barry Reisberg,Gustavo C. Román,Tohru Sawada,Leonardo Pantoni,John V. Bowler,Clive Ballard,Charles DeCarli,Philip B. Gorelick,Kenneth Rockwood,Alistair Burns,Serge Gauthier,Steven T. DeKosky +13 more
TL;DR: Findings from 5 large, randomized studies of the symptomatic treatment of probable and possible vascular dementia indicate that the presence of a cholinergic deficit is not required for the anticholinesterases to produce cognitive improvement, and so the cholin allergic hypothesis is neither necessary nor sufficient to explain the effects of these drugs.
References
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Journal ArticleDOI
“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
A practical method for grading the cognitive state of patients for the clinician
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Journal ArticleDOI
Neuropathological stageing of Alzheimer-related changes.
Heiko Braak,Eva Braak +1 more
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Journal ArticleDOI
Mild Cognitive Impairment: Clinical Characterization and Outcome
Ronald C. Petersen,Glenn E. Smith,Stephen C. Waring,Robert J. Ivnik,Eric G. Tangalos,Emre Kokmen +5 more
TL;DR: Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD, and appear to constitute a clinical entity that can be characterized for treatment interventions.