A Systematic Review and Meta-Analysis of The Effect of Low Vitamin D on Cognition

BACKGROUND/OBJECTIVE: With an aging population and no cure for dementia on the horizon, risk factor modification prior to disease onset is an urgent health priority. Therefore, this review examined the effect of low vitamin D status or vitamin D supplementation on cognition in midlife and older adults without a diagnosis of dementia. DESIGN: Systematic review and random effect meta-analysis. SETTING: Observational (cross-sectional and longitudinal cohort) studies comparing low and high vitamin D status and interventions comparing vitamin D supplementation with a control group were included in the review and meta-analysis. PARTICIPANTS: Studies including adults and older adults without a dementia diagnosis were included. MEASUREMENTS: Medline (PubMed), AMED, Psych INFO, and Cochrane Central databases were searched for articles until August 2016. The Newcastle-Ottawa Scale and Physiotherapy Evidence Database assessed methodological quality of all studies. RESULTS: Twenty-six observational and three intervention studies (n = 19-9,556) were included in the meta-analysis. Low vitamin D was associated with worse cognitive performance (OR = 1.24, CI = 1.14-1.35) and cognitive decline (OR = 1.26, CI = 1.09-1.23); with cross-sectional yielding a stronger effect compared to longitudinal studies. Vitamin D supplementation showed no significant benefit on cognition compared with control (SMD = 0.21, CI = -0.05 to 0.46). CONCLUSION: Observational evidence demonstrates low vitamin D is related to poorer cognition; however, interventional studies are yet to show a clear benefit from vitamin D supplementation. From the evidence to date, there is likely a therapeutic age window relevant to the development of disease and therefore vitamin D therapy. Longitudinal lifespan studies are necessary to depict the optimal timing and duration in which repletion of vitamin D may protect against cognitive decline and dementia in aging, to better inform trials and practice towards a successful therapy.