Title
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Cerebrovascular risk factors and preclinical memory decline in healthy APOE epsilon 4 homozygotes
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Author
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Abstract
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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 epsilon 4 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 epsilon 4 homozygotes (HMZ), 239 epsilon 4 heterozygotes (HTZ), and 494 epsilon 4 noncarriers were included. APOE epsilon 4 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 epsilon 4 carriers (p = 0.02), but had no effect in noncarriers. When epsilon 4 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 epsilon 4 carriers only that remained significant only for CIG after correction for multiple comparisons. Conclusion: CV risk factors influence age-related memory decline in APOE epsilon 4 HMZ. Neurology (R) 2011;76:1078-1084 |
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Language
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English
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Source (journal)
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Neurology / American Academy of Neurology. - Minneapolis, Minn
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Publication
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Minneapolis, Minn
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2011
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ISSN
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0028-3878
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DOI
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10.1212/WNL.0B013E318211C3AE
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Volume/pages
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76
:12
(2011)
, p. 1078-1084
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ISI
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000288853200013
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Full text (Publisher's DOI)
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