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The apolipoprotein E (ApoE) ɛ4 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 ɛ4+ and ɛ4– 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 ɛ4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on ɛ4 effects and to examine the association between ɛ4 and other behavioral symptoms. ApoE ɛ4 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 ɛ4 and delusions. The ɛ4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE ɛ4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.Neuropsychopharmacology (2007) 32, 171–179. doi:10.1038/sj.npp.1301148; published online 12 July 2006 [ABSTRACT FROM AUTHOR]

The apolipoprotein E (ApoE) epsilon4 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 epsilon4+ and epsilon4- 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 epsilon4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on epsilon4 effects and to examine the association between epsilon4 and other behavioral symptoms. ApoE epsilon4 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 epsilon4 and delusions. The epsilon4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE epsilon4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

Objective: The apolipoprotein E (ApoE) epsilon4 allele is a well-documented genetic risk factor for Alzheimer's disease (AD). Its role, if any, in the progression of cognitive and functional impairment in AD has been the subject of discrepant reports in the literature. This study aimed to determine whether ApoE epsilon4 dose is related to the progression of cognitive and functional decline in AD patients by combined retrospective and prospective analyses., Methods: A sample of 366 AD patients was genotyped for ApoE. Subjects received tests of cognition (Mini-Mental State Examination, MMSE; Alzheimer's Disease Assessment Scale-Cognitive subscale, ADAS-Cog) and daily function (Instrumental Activities of Daily Living, IADL; Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL) at baseline and at multiple subsequent time points during their participation in a variety of research protocols. In retrospective analyses, scores on baseline cognitive and functional measures were compared cross-sectionally among genotype groups, controlling for duration of symptoms. In prospective analyses, longitudinal rates of change for each measure were computed by linear regression and compared across genotype groups., Results: No association was observed between ApoE epsilon4 dose and any of the retrospective or prospective measures of cognitive or functional decline in this AD patient sample., Conclusions: Although ApoE epsilon4 increases the risk for AD and decreases the age of disease onset in population studies, it did not significantly influence the rate of disease progression in cognitive or functional domains in our sample.