Low Vitamin D Levels And Risk Of Incident Delirium In 351,000 Olderukbiobank Participants

BACKGROUND/OBJECTIVES Delirium is common in older adults, especially following hospitalization. Because low vitamin D levels may be associated with increased delirium risk, we aimed to determine the prognostic value of blood vitamin D levels, extending our previous genetic analyses of this relationship. DESIGN Prospective cohort analysis. SETTING Community-based cohort study of adults from 22 cities across the United Kingdom (the UK Biobank). PARTICIPANTS Adults aged 60 and older by the end of follow-up in the linked hospital inpatient admissions data, up to 14 years after baseline (n = 351,320). MEASUREMENTS At baseline, serum vitamin D (25-OH-D) levels were measured. We used time-to-event models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D deficiency and incident hospital-diagnosed delirium, adjusted for age, sex, assessment month, assessment center, and ethnicity. We performed Mendelian randomization genetic analysis in European participants to further investigate vitamin D and delirium risk. RESULTS A total of 3,634 (1.03%) participants had at least one incident hospital-diagnosed delirium episode. Vitamin D deficiency (<25 nmol/L) predicted a large incidence in delirium (HR = 2.49; 95% CI = 2.24-2.76;P= 3*10(-68), compared with >50 nmol/L). Increased risk was not limited to the deficient group: insufficient levels (25-50 nmol/L) were also at increased risk (HR = 1.38; 95% CI = 1.28-1.49;P= 4*10(-18)). The association was independent of calcium levels, hospital-diagnosed fractures, dementia, and other relevant cofactors. In genetic analysis, participants carrying more vitamin D-increasing variants had a reduced likelihood of incident delirium diagnosis (HR = .80 per standard deviation increase in genetically instrumented vitamin D: .73-.87;P= 2*10(-7)). CONCLUSION Progressively lower vitamin D levels predicted increased risks of incident hospital-diagnosed delirium, and genetic evidence supports a shared causal pathway. Because low vitamin D levels are simple to detect and inexpensive and safe to correct, an intervention trial to confirm these results is urgently needed.