Low Vitamin D Levels and Risk of Incident Delirium in 351,000 Older UK Biobank Participants

J Am Geriatr Soc. 2021 Feb;69(2):365-372. doi: 10.1111/jgs.16853. Epub 2020 Oct 5.


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.

Keywords: biomarker; delirium; genetic; risk factor; vitamin D.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biological Specimen Banks
  • Causality
  • Cohort Studies
  • Delirium* / blood
  • Delirium* / epidemiology
  • Delirium* / physiopathology
  • Female
  • Geriatric Assessment / methods
  • Hospitalization / statistics & numerical data*
  • Humans
  • Incidence
  • Male
  • Mendelian Randomization Analysis
  • Predictive Value of Tests
  • Risk Assessment / methods
  • Risk Factors
  • United Kingdom / epidemiology
  • Vitamin D / blood*
  • Vitamin D Deficiency* / blood
  • Vitamin D Deficiency* / epidemiology
  • Vitamin D Deficiency* / psychology


  • Vitamin D