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