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Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients.

ABSTRACT: OBJECTIVE:To identify medications that may prevent psychosis in patients with Alzheimer disease (AD). METHODS:The authors compared the frequency of medication usage among patients with AD with or without psychosis symptoms (AD?+?P versus AD - P). The authors also conducted survival analysis on time to psychosis for patients with AD to identify drugs with beneficial effects. The authors further explored the potential molecular mechanisms of identified drugs by gene-signature analysis. Specifically, the gene expression profiles induced by the identified drug(s) were collected to derive a list of most perturbed genes. These genes were further analyzed by the associations of their genetic variations with AD or psychosis-related phenotypes. RESULTS:Vitamin D was used more often in AD - P patients than in AD?+?P patients. Vitamin D was also significantly associated with delayed time to psychosis. AD and/or psychosis-related genes were enriched in the list of genes most perturbed by vitamin D, specifically genes involved in the regulation of calcium signaling downstream of the vitamin D receptor. CONCLUSION:Vitamin D was associated with delayed onset of psychotic symptoms in patients with AD. Its mechanisms of action provide a novel direction for development of drugs to prevent or treat psychosis in AD. In addition, genetic variations in vitamin D-regulated genes may provide a biomarker signature to identify a subpopulation of patients who can benefit from vitamin D treatment.

SUBMITTER: Wang L

PROVIDER: S-EPMC6693492 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients.

Wang Lirong L Ying Jian J Fan Peihao P Weamer Elise A EA DeMichele-Sweet Mary Ann A MAA Lopez Oscar L OL Kofler Julia K JK Sweet Robert A RA

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20190327 9

<h4>Objective</h4>To identify medications that may prevent psychosis in patients with Alzheimer disease (AD).<h4>Methods</h4>The authors compared the frequency of medication usage among patients with AD with or without psychosis symptoms (AD + P versus AD - P). The authors also conducted survival analysis on time to psychosis for patients with AD to identify drugs with beneficial effects. The authors further explored the potential molecular mechanisms of identified drugs by gene-signature analys ...[more]

PMID: 31126722

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Project description:ImportanceNeuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.ObjectiveTo evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.Design, setting, and participantsThis cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions.Main outcomes and measuresAll individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET).ResultsOf the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β = 7.37; 95% CI, 1.34-13.41; P = .01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β = 6.86; 95% CI, 1.77-11.95; P = .008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β = 5.72; 95% CI, 0.33-11.10; P = .03).Conclusions and relevanceIn this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.

Dataset Information

Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients.

Publications

Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients.

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