Background: Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer�s\r\ndisease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are\r\ngenerally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than\r\npatients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would\r\nfacilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and\r\nmortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the\r\ndevelopment of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced\r\nconflicting findings.\r\nMethods: This study investigates the association between APOE and neuropsychiatric symptoms in a large sample\r\nof clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the\r\nConsortium to Establish a Registry for Alzheimer�s Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD).\r\nResults: Our study found that hallucinations were significantly more likely to occur in subjects with no APO?4\r\nalleles than in subjects with two ?4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas\r\nthere was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the\r\nnumber of ?4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H).\r\nConclusion: These findings suggest that in AD the ?4 allele is differentially associated with D+H but not delusions\r\nalone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the\r\nAPOE allele.
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