Neurology. 2019 Feb 15. pii: 10.1212/WNL.0000000000007136.
Bowman K1, Jones L1, Pilling LC1, Delgado J1, Kuchel GA1, Ferrucci L1, Fortinsky RH1, Melzer D2.
- Hospital induced delirium 2X more likely if low vitamin D – April 2015
- Delirium in Hospitalized Older Adults (does not mention low vitamin D relationship) NEJM Oct 2017
- Delirium 2.7 X more likely after hip fracture and low vitamin D – May 2015
- Post-surgery delirium in critically ill 1.4X more likely for each 10 ng lower level of vitamin D (below 30 ng) – July 2021
OBJECTIVE: To estimate effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models, which minimize confounding and exclude reverse causation.
Longitudinal analysis using the UK Biobank, community-based, volunteer cohort (2006-2010) with incident hospital-diagnosed delirium (ICD-10 F05) ascertained during ≤9.9 years of follow-up of hospitalization records (to early 2016). We included volunteers of European descent aged 60-plus years by end of follow-up. We used single-nucleotide polymorphisms previously shown to increase circulating vitamin D levels, and APOE variants. Cox competing models accounting for mortality were used.
Of 313,121 participants included, 544 were hospitalized with delirium during follow-up. Vitamin D variants were protective for incident delirium: hazard ratio = 0.74 per 10 nmol/L (95% confidence interval 0.62-0.87, p = 0.0004) increase in genetically instrumented vitamin D, with no evidence for pleiotropy (mendelian randomization-Egger p > 0.05). Participants with ≥1 APOE ε4 allele were more likely to develop delirium (e.g., ε4ε4 hazard ratio = 3.73, 95% confidence interval 2.68-5.21, p = 8.0 × 10-15 compared to ε3ε3), but there was no interaction with vitamin D variants.
CONCLUSIONS AND RELEVANCE:
In a large community-based cohort, there is genetic evidence supporting a causal role for vitamin D levels in incident delirium. Trials of correction of low vitamin D levels in the prevention of delirium are needed.
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