The neuropsychology of normal aging and preclinical Alzheimer's disease

Richard J. Caselli, Dona E.C. Locke, Amylou C. Dueck, David S. Knopman, Bryan K. Woodruff, Charlene Hoffman-Snyder, Rosa Rademakers, Adam S. Fleisher, Eric M. Reiman

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Objective: A National Institute on Aging-sponsored work group on preclinical Alzheimer's disease (AD) articulated the need to characterize cognitive differences between normal aging and preclinical AD. Methods: Seventy-one apolipoprotein E (APOE) ε4 homozygotes, 194 ε3/ε4 heterozygotes, and 356 ε4 noncarriers age 21 to 87 years who were cognitively healthy underwent neuropsychological testing every 2 years. Longitudinal trajectories of test scores were compared between APOE subgroups. Results: There was a significant effect of age on all cognitive domains in both APOE ε4 carriers and noncarriers. A significant effect of APOE ε4 gene dose was confined to the memory domain and the Dementia Rating Scale. Cross-sectional comparisons did not discriminate the groups. Conclusions: Although cognitive aging patterns are similar in APOE ε4 carriers and noncarriers, preclinical AD is characterized by a significant ε4 gene dose effect that impacts memory and is detectable longitudinally. Preclinical neuropsychological testing strategies should emphasize memory-sensitive measures and longitudinal design.

Original languageEnglish (US)
Pages (from-to)84-92
Number of pages9
JournalAlzheimer's and Dementia
Issue number1
StatePublished - Jan 2014


  • Age-related memory loss
  • Apolipoprotein E
  • Cognitive aging
  • Longitudinal testing
  • Mild cognitive impairment
  • Preclinical Alzheimer's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Health Policy
  • Developmental Neuroscience
  • Epidemiology


Dive into the research topics of 'The neuropsychology of normal aging and preclinical Alzheimer's disease'. Together they form a unique fingerprint.

Cite this