APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease

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Abstract
Objective: To determine whether APOE ε4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). Methods: Individuals were recruited from two longitudinal cohort studies—the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)—and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of ε4 status in each sample. Results: The presence of at least one ε4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. Conclusion: APOE ε4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.

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