Age and apolipoprotein E genotype influence rate of cognitive decline in nondemented elderly

David P. Salmon, Steven H. Ferris, Ronald G. Thomas, Mary Sano, Jeffery L. Cummings, Reisa A. Sperling, Ronald C. Petersen, Paul S. Aisen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objective: This study examined the impact of age and apolipoprotein E (APOE) genotype on the rate of cognitive decline in nondemented elderly participants in a simulated Alzheimer's disease (AD) primary prevention treatment trial carried out by the Alzheimer's Disease Cooperative Study. Method: Cognitive tests were administered at baseline and at four subsequent annual evaluations to 417 nondemented participants (172 men, 245 women) between the ages of 74 and 93 (M = 79.13 ± 3.34). APOE genotyping was available for 286 of the participants. Results: Four-year decline was evident on measures of orientation, memory, executive function, and language. Faster decline was evident in APOE ε4+ (a genetic risk factor for AD; n = 73) than in ε4- participants (n = 213), even after controlling for education, gender, ethnicity, and baseline functional and cognitive abilities. This discrepancy increased with age, indicating an Age × Genotype interaction. Conclusion: These results are consistent with population-based studies, and extend the findings to a carefully screened sample that meets inclusion and exclusion criteria for an AD primary prevention trial. The interaction between age and APOE genotype on rate of decline suggests that preclinical disease may be overrepresented in older ε4+ individuals. Thus, APOE genotype and age should be considered in the design of AD primary prevention treatment trials.

Original languageEnglish (US)
Pages (from-to)391-401
Number of pages11
Issue number4
StatePublished - Jul 2013


  • Aging
  • Apolipoprotein E
  • Cognitive decline

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology


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