Abstract
Approximately 50% of late-onset Alzheimer's disease (AD) patients develop psychosis (AD+P), a heritable phenotype associated with more rapid cognitive decline. Prior studies conflict regarding whether apolipoprotein E (APOE) ϵ4 alleles are associated with AD+P, possibly due to small sample sizes, inconsistent diagnostic criteria, and different methodologies to assess psychosis. We used the National Alzheimer's Coordinating Center Uniform Data Set to evaluate the largest uniformly characterized sample of AD+P subjects studied to date for the association of APOE ϵ4 genotype, along with other demographic and clinical variables. Greater cognitive impairment and depressive symptoms were associated with AD+P, while the Caucasian race was protective. Neither APOE ϵ4 carrier status nor allele number was associated with psychosis. The AD+P phenotype is not associated with the APOE ϵ4 genotype. AD+P may represent a useful phenotype for the discovery of non-APOE ϵ4 genetic variation contributing to the risk of AD.
Highlights
Psychotic symptoms, delusions, and hallucinations are common in Alzheimer’s disease (AD; Alzheimer’s disease plus psychosis (AD+P)), occurring in approximately 40% of individuals over the course of the illness [1]
We have identified 22 studies that examined the association of the apolipoprotein E (APOE) 4 allele with AD+P, with nine reporting that 4 increased the risk for AD+P, whereas 13 studies found no effect of 4 [12]
The Uniform Data Set (UDS) was developed by National Alzheimer’s Coordinating Center (NACC) to provide the Alzheimer’s Disease Centers (ADC) with standardized assessments thereby allowing uniformity amongst centers when diagnosing these subjects with mild cognitive impairment or Alzheimer’s disease [13]
Summary
Delusions, and hallucinations are common in Alzheimer’s disease (AD; AD+P), occurring in approximately 40% of individuals over the course of the illness [1]. Ropacki and Jeste [1] comprehensively reviewed the literature on psychosis in AD. They reviewed 55 studies comprised of 9,749 subjects. The most consistent correlate of AD+P was greater cognitive impairment than is found in AD without psychosis (AD−P). Studies conducted more recently have continued to support the relationship between greater cognitive impairment and AD+P [9, 10]. AD+P may be associated with race, though it has only been examined in a limited number of studies to date [1]. Few variables are examined in all studies; sample sizes of individual studies were not always sufficient to detect small-to-moderate effects, and approaches to characterization of subjects, including identification of psychosis, varied considerably
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