High Body Mass Index as a Causal Risk Factor for Vascular-Related Dementia: A Mendelian Randomization Study
Authors' conclusion
Observationally (U-shaped) and genetically (linearly), high BMI is associated with a higher risk of vascular-related dementia, an association partly mediated through high blood pressure. This suggests that high BMI and high blood pressure are important modifiable risk factors for dementia prevention.
Study context
- Population
- General-population prospective cohorts from the Copenhagen area and across the UK, plus consortia data
- Comparison
- Genetically predicted 1-SD higher body mass index (BMI)
- Outcome
- Risk of vascular-related dementia
Methodological detailsone-sample mendelian randomization (MR), two-sample MR, MR mediation analyses, individual-level and summary-level data
- One-sample MR
- Two-sample MR
- MR mediation analyses
- Individual-level and summary-level data
Main finding
As reported in the abstract
OR, meta-analysis of 2 one-sample MR studies
1.63
95% CI 1.13–2.35
OR, two-sample MR, inverse-variance weighted
1.54
1.10–2.16
OR, two-sample MR, weighted median
1.87
1.22–2.85
OR, two-sample MR, weighted mode
1.98
1.21–3.22
Further findings
MR analyses with extended numbers of genetic variants
- Results directionally consistent
Mediation of genetic effect of BMI on vascular-related dementia
- Mediated by systolic blood pressure
- 18% (95% CI, 10%-61%)
- Mediated by diastolic blood pressure
- 25% (13%-75%)
Original publication
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