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From the Departments of Neurology (Dr. Farlow), Psychiatry (Dr. Lahiri), and Medicine (Dr. Hui), Indiana University School of Medicine, Indianapolis, IN; the McGill Center for Studies in Aging (Dr. Poirier), Douglas Hospital Research Center, McGill University, Quebec, Canada; the Clinical Research Institute (Dr. Davignon), Montreal, Canada; and the Department of Psychiatry and the Behavioral Sciences (Dr. Schneider), University of Southern California, Los Angeles, CA.
Address correspondence and reprint requests to Dr. Martin R. Farlow, Indiana University School of Medicine, Department of Neurology, 541 North Clinical Drive, Suite 583, Indianapolis, IN 46202-5111.
We studied the effects of apolipoprotein E (APOE) genotype and gender on clinical response to tacrine in patients with mild to moderate Alzheimer's disease (AD). We analyzed data from a previously reported 30-week, double-blind, placebo-controlled trial of tacrine, in which APOE genotypes were determined from previously collected plasma samples. Patients were assigned to placebo or tacrine with daily dosages of 80, 120, or 160 mg/day. The outcome measures were Alzheimer's Disease Assessment Scale-Cognitive Component, Clinician Interview Based Impression, Mini-Mental State Examination, and the Caregiver-rated Clinical Global Impression of Change. An intent-to-treat (ITT) analysis of patients with available genotypes (n = 528) did not reveal response differences by genotype, although the effect size was twice as large in the 
2-3 as the4 group (-2.62 versus -1.25). The association of treatment effect with APOE genotype varied significantly according to gender (p< 0.002 for ITT; p < 0.05 for evaluables). The treatment effect was larger in the 2-3 compared with 4 women (ITT, 4.24 points, p = 0.03; evaluable, 7.20 points, p = 0.01). In contrast, treatment effect size was not different between 2-3 and4 of men with AD. APOE genotype and gender may predict response to tacrine in patients with AD.
Supported in part by NIA Grant No. 10133 (Indiana University School of Medicine Alzheimer Disease Center), NIA Grant No. 05142 (Southern California Alzheimer's Disease Research Center Consortium), and Warner-Lambert/Parke Davis Pharmaceuticals, Inc., Ann Arbor, MI.
Presented in part at the 48th annual meeting of the American Academy of Neurology, San Francisco, CA, March 1996.
Received February 15, 1997. Accepted in final form October 2, 1997.
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