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Published online before print April 9, 2008, doi:10.1212/01.wnl.0000304038.37421.cc)
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Received July 5, 2007
Accepted October 22, 2007

APOE {epsilon}4 allele predicts faster cognitive decline in mild Alzheimer disease

S. Cosentino PhD, N. Scarmeas MD, E. Helzner PhD, M. M. Glymour PhD, J. Brandt PhD, M. Albert PhD, D. Blacker MD, PhD, and Y. Stern PhD*

From the Cognitive Neuroscience Division of the Gertrude H. Sergievsky Center (S.C., N.S., Y.S.), the Taub Institute for Research in Alzheimer's Disease and the Aging Brain (N.S., Y.S., E.H.), and the Department of Neurology (N.S., Y.S.), Columbia University Medical Center, New York; Department of Epidemiology (M.M.G.), Mailman School of Public Health, Columbia University, New York, NY; the Departments of Neurology (J.B., M.A.), and Psychiatry and Behavioral Sciences (J.B., M.A.), Johns Hopkins University School of Medicine, Baltimore, MD; and the Department of Psychiatry (D.B.), Massachusetts General Hospital, Harvard Medical School, Boston.


* To whom correspondence should be addressed. E-mail: ys11{at}columbia.edu.

Objective: To determine whether APOE {epsilon}4 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 {epsilon}4 status in each sample.

Results: The presence of at least one {epsilon}4 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 {epsilon}4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.




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