Highlights
- •Vitamin D was used more often in patients of Alzheimer's disease without psychosis symptoms than in patients of Alzheimer's disease with psychosis symptoms.
- •Vitamin D use was significantly associated with delayed time to psychosis in Alzheimer's disease patients.
- •The molecular mechanism of the beneficial effect might be attributed to the facts that Vitamin D can regulate Alzheimer's disease and/or psychosis-related genes.
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.
Key Words
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Article info
Publication history
Published online: March 27, 2019
Accepted:
March 21,
2019
Received in revised form:
March 13,
2019
Received:
May 22,
2018
Identification
Copyright
© 2019 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
