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Apolipoprotein E genotype and lifetime cognitive decline

Published online by Cambridge University Press:  01 February 2008

Nicholas A. Kozauer*
Division of Geriatric and Neuropsychiatry, Johns Hopkins School of Medicine, Baltimore, U.S.A.
Michelle M. Mielke
Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatr, Johns Hopkins School of Medicine, Baltimore, U.S.A.
Gary Kwun Chuen Chan
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, U.S.A.
George W. Rebok
Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, U.S.A.
Constantine G. Lyketsos
The Johns Hopkins Bayview Medical Center Department of Psychiatry and Division of Geriatric and Neuropsychiatry, The Johns Hopkins Hospital, Baltimore, U.S.A.
Correspondence should be addressed to: Dr. Nicholas A. Kozauer, Division of Geriatric and Neuropsychiatry, Johns Hopkins School of Medicine, 550 N. Broadway, Suite 308, Baltimore, MD 21205. Phone +1 410 502 3748; Fax +1 410 614 8042. Email:


Objective: The relationship of apolipoprotein E (APOE) genotype to lifetime cognitive decline was examined over 22 years in a large community-based population study.

Method: The sample for the present study was derived from follow-up of a probability sample of the adult household residents of East Baltimore. From the Baltimore cohort of the Epidemiologic Catchment Area Study, genotype data were collected on 818 participants at the study's fourth wave between 2003 and 2004. Participants were administered the Mini-mental State Examination (MMSE) at all four study waves. Three tests of verbal learning – immediate recall, delayed recall, and word recognition – were completed at waves 3 and 4. The 659 participants for whom genetic data were available had also completed cognitive testing at all time points. Test scores and changes in these scores were examined by APOE genotype group (x/x or 4/x) in younger and older subcohorts defined by age at wave 4 (< or ≥ age 65).

Results: Cross-sectional wave 4 scores on all four cognitive tasks were lower in APOEε4 carriers when compared to non-carriers. In longitudinal univariate models ε4 carriers in the younger cohort demonstrated a greater annual rate of decline on a delayed recall task and MMSE. After adjusting for covariates only the decline in the delayed recall task was significant.

Conclusion: We report an association between APOE genotype and decline in delayed recall and possibly MMSE over this extended time period limited to younger individuals. The lack of an association between APOE and decline in older individuals is likely to be the result of survival bias. Although a clear association exists between APOE genotype and cognitive decline or dementia in late life, these findings suggest that over the lifespan the relationship between APOE and cognitive decline is more complicated.

Research Article
Copyright © International Psychogeriatric Association 2007

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