Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer's disease Patients

Objective To identify medications which may prevent psychosis in Alzheimer's disease (AD) patients. Methods We compared the frequency of medication usage among AD patients with or without psychosis symptoms (AD+P vs. AD-P). We also conducted survival analysis on time to psychosis for AD patients to identify drugs with beneficial effects. We 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 AD patients. 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.