Title: Vitamin D levels and risk of delirium: A mendelian randomization study in the UK Biobank
Published in: Neurology, 2019
## Objective
– To estimate the effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models
## Methods
– Study design: Longitudinal analysis using the UK Biobank cohort
– Participants: 313,121 community-based volunteers of European descent aged 60+ years
– Follow-up period: Up to 9.9 years (mean 4.6 years)
– Outcome: Incident hospital-diagnosed delirium (ICD-10 F05)
– Genetic variants used:
– 6 single-nucleotide polymorphisms (SNPs) associated with vitamin D levels
– APOE variants
– Analysis: Cox competing models accounting for mortality
## Key Findings
1. Incident delirium cases:
– 544 participants were hospitalized with delirium during follow-up
– Mean age at delirium diagnosis: 71.6 years (SD 4.12 years)
2. Vitamin D genetic associations:
– Vitamin D-increasing alleles were associated with decreased risk of delirium
– Hazard ratio (HR) = 0.74 per 10 nmol/L increase in genetically instrumented vitamin D (95% CI 0.62-0.87, p=0.0004)
– No evidence for pleiotropy (MR-Egger p>0.05)
3. APOE associations:
– Participants with ≥1 APOE ε4 allele were more likely to develop delirium
– APOE ε4ε4 homozygotes: HR = 3.73 (95% CI 2.68-5.21, p=8.0 × 10^-15) compared to ε3ε3
– No interaction between APOE status and vitamin D variants
4. Sensitivity analyses:
– Results remained consistent after adjusting for time spent outdoors, excluding related participants, and adjusting for calcium genetic risk score
– Excluding prevalent dementia cases did not affect the associations
## Conclusions
– Genetic evidence supports a causal role for vitamin D levels in incident delirium
– The study suggests that trials of vitamin D supplementation for delirium prevention may be warranted
## Limitations
– Study limited to participants of European descent
– Delirium diagnoses based on hospital discharge data, potentially missing milder cases
– Unable to account for potential environmental confounders
## Implications
– Findings suggest that maintaining adequate vitamin D levels may help reduce the risk of delirium in older adults
– Further research needed to determine optimal vitamin D levels for delirium prevention
Citations:
[1] https://ppl-ai-file-upload.s3.amazonaws.com/web/direct-files/27176464/d014149f-dad3-43af-aa71-c61a27d034c3/NEUROLOGY2018905778.pdf
