Neuropsychological markers of cognitive decline in persons with Alzheimer disease neuropathology

Jason Hassenstab, Sarah E. Monsell, Charles Mock, Catherine M. Roe, Nigel J. Cairns, John C. Morris, Walter Kukull

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropa-thology 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.

Original languageEnglish
Pages (from-to)1086-1092
Number of pages7
JournalJournal of neuropathology and experimental neurology
Volume74
Issue number11
DOIs
StatePublished - Jan 1 2015

Keywords

  • Alzheimer disease
  • Braak staging
  • Clinical diagnosis
  • Consortium to Establish a Registry for Alzheimer's Disease (CERAD) plaque
  • Memory
  • Mild cognitive impairment
  • Neuropathology

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