Apolipoprotein E epsilon 4 allele increases risk for psychotic symptoms in Alzheimer's disease

The apolipoprotein E (ApoE) epsilon 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 epsilon 4+ and epsilon 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 epsilon 4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on epsilon 4 effects and to examine the association between epsilon 4 and other behavioral symptoms. ApoE epsilon 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 MMSF 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 epsilon 4 and delusions. The epsilon 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 epsilon 4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.