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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 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.
Footnotes
-
Study funding: Supported by the National Institute on Aging (P30-AG19610 and R01-AG031581), the National Institute of Mental Health (R01-MH057899), the Alzheimer's Association (IIRG-98-078), the Arizona Alzheimer's Consortium, the State of Arizona, and with resources from Southern Arizona VA Health Care System.
-
- AD
- Alzheimer disease
- AVLT
- Auditory Verbal Learning Test
- CHOL
- hypercholesterolemia
- CI
- confidence interval
- CIG
- cigarette use
- CV
- cerebrovascular
- CVany
- any of 4 cerebrovascular risk factors
- DM
- diabetes mellitus
- DSM-III-R
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised
- FAQ
- Functional Activities Questionnaire
- Ham-D
- Hamilton Depression Rating Scale
- HMZ
- homozygotes
- HTN
- hypertension
- HTZ
- heterozygote
- IADL
- Instrumental Activities of Daily Living
- LTM
- long-term memory
- MCI
- mild cognitive impairment
- MMSE
- Mini-Mental State Examination
-
Supplemental data at www.neurology.org
- Received September 2, 2010.
- Accepted November 18, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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