25-hydroxyvitamin D concentrations and risk of incident dementia, mild cognitive impairment, and delirium in 443,427 UK Biobank participants

This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and dementia, mild cognitive impairment (MCI), and delirium. Participants from the United Kingdom (UK) Biobank with complete information on serum 25(OH)D concentrations were enrolled. Dementia, MCI and delirium were defined using the UK Biobank algorithm. 443,427 participants with a mean (standard deviation) age of 56.8 (8.0) years were included in this study. Based on Cox regression models, serum 25(OH)D concentrations were inversely associated with the risk of dementia, MCI, and delirium in a dose-dependent manner after adjusting for demographics (P-trend <0.001). In comparison with 25(OH)D levels less than 32.4 nmol/L, participants with the highest 25(OH)D levels (i.e., >64.4 nmol/L) had the lowest risk of dementia (hazards ratio [HR]: 0.58, 95% confidence interval [CI] 0.49-0.69, P<0.001), MCI (HR: 0.55, 95% CI 0.37-0.84, P=0.005), and delirium (HR: 0.63, 95% CI 0.51-0.79, P<0.001). These results were consistent with the sensitivity analysis, in which participants with events occurring within the first two years of follow-up were excluded. This study found that a lower serum 25(OH)D concentration was significantly associated with a higher risk of dementia (including Alzheimer's disease and vascular dementia), MCI, and delirium.