Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes
OBJECTIVE: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype. METHODS: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two. RESULTS: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p=0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons. CONCLUSION: CV risk factors influence age-related memory decline in APOE ε4 HMZ.
Medical Subject Headings
Adult; Aging (genetics, psychology); Alzheimer Disease (complications, genetics, psychology); Apolipoprotein E4 (genetics); Cerebrovascular Circulation (genetics); Cognition; Female; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Longitudinal Studies; Male; Memory Disorders (complications, genetics); Memory, Long-Term; Middle Aged; Neuropsychological Tests; Risk Factors
Digital Object Identifier (DOI)
Caselli, R J.; Dueck, A C.; Locke, D E.; Sabbagh, M N.; Ahern, G L.; Rapcsak, S Z.; Baxter, L C.; Yaari, R; Woodruff, B K.; Hoffman-Snyder, C; Rademakers, R; Findley, S; and Reiman, E M., "Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes" (2011). Neurology. 794.