1. ¹Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, CT, USA
2. ²Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
3. ³Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr CH van Dyck, Alzheimer's Disease Research Unit, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA. Tel: +1 203 764 8100, Fax: +1 203 764 8111, E-mail: christopher.vandyck@yale.edu

Received 27 December 2005; Revised 20 April 2006; Accepted 25 May 2006; Published online 12 July 2006.

Abstract

The apolipoprotein E (ApoE) 4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE 4+ and 4– AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n=266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE 4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on 4 effects and to examine the association between 4 and other behavioral symptoms. ApoE 4 was significantly associated with psychotic symptoms (odds ratio (OR)=1.87, 95% CI=1.07–3.29, P=0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between 4 and delusions. The 4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE 4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.