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Gender and Pathology-Specific Effect of Apolipoprotein E Genotype on Psychosis in Alzheimer's Disease.

ABSTRACT: Symptoms of psychosis is one of the common clinical manifestations of Alzheimer's disease (AD). However, the pathophysiology behind psychosis is unknown.The aim of the present study was to explore the relationship between Apolipoprotein E (APOE) genotype, Lewy body pathology, and psychosis in AD.The data was obtained from the National Alzheimer's disease Coordinating Centre (NACC), using the Uniform Data Set and the Neuropathology Data Set. Subjects with frequent neuritic plaque on CERAD, and Braak Stage of V or VI, corresponding to high probability of AD based on the NIA-AA Regan criteria were included in the analysis.Subjects with two copies of ?4 alleles were significantly more likely to develop psychosis, both delusions and/or hallucinations, during the course of their illness. This association was gender-specific, only reaching significance in females. Our findings further showed that presence of two copies of ?4 allele was positively associated with the formation of Lewy bodies. Only in females with Lewy bodies was the effect of two copies of ?4 allele significant, reaching an odd ratio of 4.5.The APOE ?4 allele has a female-specific effect in inducing psychosis in AD through the formation of Lewy bodies.

SUBMITTER: Kim J

PROVIDER: S-EPMC5837801 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Gender and Pathology-Specific Effect of Apolipoprotein E Genotype on Psychosis in Alzheimer's Disease.

Kim Julia J Fischer Corinne E CE Schweizer Tom A TA Munoz David G DG

Current Alzheimer research 20170101 8

<h4>Background</h4>Symptoms of psychosis is one of the common clinical manifestations of Alzheimer's disease (AD). However, the pathophysiology behind psychosis is unknown.<h4>Objective</h4>The aim of the present study was to explore the relationship between Apolipoprotein E (APOE) genotype, Lewy body pathology, and psychosis in AD.<h4>Method</h4>The data was obtained from the National Alzheimer's disease Coordinating Centre (NACC), using the Uniform Data Set and the Neuropathology Data Set. Sub ...[more]

PMID: 28219318

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Project description:BACKGROUND:Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ?4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. OBJECTIVE:We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ?4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ?4, Lewy bodies, and psychosis. METHODS:Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ?4, as well as their interaction. RESULTS:Psychosis and the presence of APOE ?4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ?4 on MMSE scores, with APOE ?4 negatively affecting patients with hallucinations-only psychosis. APOE ?4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. CONCLUSION:Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ?4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ?4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

Dataset Information

Gender and Pathology-Specific Effect of Apolipoprotein E Genotype on Psychosis in Alzheimer's Disease.

Publications

Gender and Pathology-Specific Effect of Apolipoprotein E Genotype on Psychosis in Alzheimer's Disease.

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