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From the Cognitive Neuroscience Division (Drs. Scarmeas and Stern), Taub Institute for Research in Alzheimer’s Disease and the Aging Brain, and Departments of Neurology (Drs. Scarmeas, Marder, Bell, and Stern), Psychiatry (Drs. Devanand and Stern), and Pathology (Drs. Ciappa and Tycko), and Gertrude H. Sergievsky Center (Drs. Scarmeas, Devanand, Marder, Bell, and Stern), Columbia University College of Physicians and Surgeons, New York, NY; Department of Psychiatry and Behavioral Sciences (Dr. Brandt), Johns Hopkins University, Baltimore, MD; and Departments of Psychiatry and Neurology (Dr. Albert), Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Dr. Yaakov Stern, Gertrude H. Sergievsky Center, 630 W. 168 St., New York, NY 10032; e-mail: ys11{at}columbia.edu
Background: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results.
Objective: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD.
Methods: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor).
Results: The presence of one 
4 allele carried a 2.5-fold risk, whereas the presence of two 4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two 4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression.
Conclusion: The presence of one or more 4 alleles is a significant predictor for the incidence of delusions in the course of AD.
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