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Genetic influences on memory performance in familial Alzheimer disease

From the Gertrude H. Sergievsky Center (Drs. Lee, Stern, and Mayeux), Taub Institute for Research on Alzheimer’s Disease and Aging Brain (Drs. Lee, Stern, Tycko, and Mayeux, A. Flaquer), and Departments of Neurology (Drs. Stern and Mayeux), Pathology (Dr. Tycko), and Psychiatry (Dr. Mayeux), College of Physicians and Surgeons, and Department of Epidemiology (Drs. Lee and Mayeux), School of Public Health, Columbia University, New York, NY.

Address correspondence and reprint requests to Dr. R. Mayeux, G.H. Sergievsky Center, Columbia University, 630 W. 168 St., New York, NY 10032; e-mail: rpm2{at}columbia.edu

Objective: To investigate the heritability of memory and other cognitive measures in families with multiple individuals with Alzheimer disease (AD) to determine if neuropsychological measures can be used to better understand genetic contributions to AD.

Methods: The genetic contributions to the variation in declarative memory, attention, abstract reasoning, language, and visuospatial function using a variance component method were estimated. For memory scores, the proportion of genetic contribution was estimated, controlling for APOE.

Results: The unadjusted heritability estimates for the declarative memory tasks ranged from 0.47 for delayed recall to 0.25 for delayed recognition, where a heritability estimate of 1 indicates that genetic factors explain all of the phenotypic variance and a heritability score of 0 indicates that genetic factors explain none. When adjusted for sex, age, education, and general intelligence, the heritability estimates increased to 0.60 for delayed recall and 0.41 for delayed recognition. None of the other cognitive tests showed heritability estimates as high as that observed for memory. When the influence of APOE was taken into account, the heritability estimates changed modestly for delayed recall and consistent long-term retrieval, whereas the estimates for other memory scores did not change, suggesting that APOE contributes little to these memory scores.

Conclusions: Declarative memory in familial AD is under strong genetic influence, only part of which is attributable to APOE. Memory performance should prove to be a useful phenotypic component in the investigation of the genetic basis of AD.

Received March 31, 2003. Accepted in final form October 6, 2003.

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