title: Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology.
abstract: To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD.
authors.affiliation: From the Knight Alzheimer's Disease Research Center, Department of Neurology (JH, CMR, NJC, JCM), Washington University School of Medicine, St. Louis, Missouri; and National Alzheimer's Coordinating Center (SEM, CM, WK), University of Washington, Seattle, Washington.
authors.forename: Jason
authors.initials: J
authors.lastname: Hassenstab
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Monsell
authors.forename: Charles
authors.initials: C
authors.lastname: Mock
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Roe
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Walter
authors.initials: W
authors.lastname: Kukull
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications*; D001288:Attention; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D006801:Humans; D007802:Language; D008297:Male; D008568:Memory; D008875:Middle Aged; D009422:Nervous System Diseases / Q000150:complications*; D009483:Neuropsychological Tests; D012189:Retrospective Studies