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Context-specific memory and apolipoprotein E (ApoE) ε4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease


The aim of the study was to determine whether the ε4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the ε4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale–Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of ε4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an ε4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative ε4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. (JINS, 2004, 10, 362–370.)

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Address correspondence and reprint requests to: James A. Levy, National Institute of Mental Health, Geriatric Psychiatry Branch, 9000 Rockville Pike, Building 10-3N228, MSC 1275, Bethesda, MD 20892. E-mail:
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