A systematic review and meta-analysis of the effect of low vitamin D on cognition

BACKGROUND/OBJECTIVE:With an aging populationand no cure for dementia on the horizon, risk factor modi-fication prior to disease onset is an urgent health priority.Therefore, this review examined the effect of low vitaminD status or vitamin D supplementation on cognition inmidlife and older adults without a diagnosis of dementia.DESIGN:Systematic review and random effect meta-ana-lysis.SETTING:Observational (cross-sectional and longitudinalcohort) studies comparing low and high vitamin D statusand interventions comparing vitamin D supplementationwith a control group were included in the review andmeta-analysis.PARTICIPANTS:Studies including adults and olderadults without a dementia diagnosis were included.MEASUREMENTS:Medline (PubMed), AMED, PsychINFO, and Cochrane Central databases were searched forarticles until August 2016. The Newcastle-Ottawa Scaleand Physiotherapy Evidence Database assessed method-ological quality of all studies.RESULTS:Twenty-six observational and three interven-tion studies (n=19–9,556) were included in the meta-ana-lysis. Low vitamin D was associated with worse cognitiveperformance (OR=1.24, CI=1.14–1.35) and cognitivedecline (OR=1.26, CI=1.09–1.23); with cross-sectionalyielding a stronger effect compared to longitudinal studies.Vitamin D supplementation showed no significant benefiton cognition compared with control (SMD=0.21,CI= 0.05 to 0.46).CONCLUSION:Observational evidence demonstrateslow vitamin D is related to poorer cognition; however,interventional studies are yet to show a clear benefit fromvitamin D supplementation. From the evidence to date,there is likely a therapeutic age window relevant to thedevelopment of disease and therefore vitamin D therapy.Longitudinal lifespan studies are necessary to depict theoptimal timing and duration in which repletion of vitaminD may protect against cognitive decline and dementia inaging, to better inform trials and practice towards a suc-cessful therapy.