Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes

R. J. Caselli, A. C. Dueck, D. E C Locke, M. N. Sabbagh, Geoffrey L Ahern, Steven Z Rapcsak, L. C. Baxter, R. Yaari, B. K. Woodruff, C. Hoffman-Snyder, R. Rademakers, S. Findley, E. M. Reiman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1078-1084
Number of pages7
JournalNeurology
Volume76
Issue number12
DOIs
StatePublished - Mar 22 2011

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Long-Term Memory
Homozygote
Verbal Learning
Heterozygote
Tobacco Products
Diabetes Mellitus
Genotype
Hypertension
Statistical Models
Hypercholesterolemia
Alzheimer Disease
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Clinical Neurology

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Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes. / Caselli, R. J.; Dueck, A. C.; Locke, D. E C; Sabbagh, M. N.; Ahern, Geoffrey L; Rapcsak, Steven Z; Baxter, L. C.; Yaari, R.; Woodruff, B. K.; Hoffman-Snyder, C.; Rademakers, R.; Findley, S.; Reiman, E. M.

In: Neurology, Vol. 76, No. 12, 22.03.2011, p. 1078-1084.

Research output: Contribution to journalArticle

Caselli, RJ, Dueck, AC, Locke, DEC, Sabbagh, MN, Ahern, GL, Rapcsak, SZ, Baxter, LC, Yaari, R, Woodruff, BK, Hoffman-Snyder, C, Rademakers, R, Findley, S & Reiman, EM 2011, 'Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes', Neurology, vol. 76, no. 12, pp. 1078-1084. https://doi.org/10.1212/WNL.0b013e318211c3ae
Caselli, R. J. ; Dueck, A. C. ; Locke, D. E C ; Sabbagh, M. N. ; Ahern, Geoffrey L ; Rapcsak, Steven Z ; Baxter, L. C. ; Yaari, R. ; Woodruff, B. K. ; Hoffman-Snyder, C. ; Rademakers, R. ; Findley, S. ; Reiman, E. M. / Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes. In: Neurology. 2011 ; Vol. 76, No. 12. pp. 1078-1084.
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AU - Caselli, R. J.

AU - Dueck, A. C.

AU - Locke, D. E C

AU - Sabbagh, M. N.

AU - Ahern, Geoffrey L

AU - Rapcsak, Steven Z

AU - Baxter, L. C.

AU - Yaari, R.

AU - Woodruff, B. K.

AU - Hoffman-Snyder, C.

AU - Rademakers, R.

AU - Findley, S.

AU - Reiman, E. M.

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N2 - 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.

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