To determine if high body mass index (BMI) is a causal risk factor for vascular-related dementia and if this effect is mediated by hypertension, hyperlipidemia, hyperglycemia, and low-grade inflammation.
Key Findings:
In a meta-analysis, the OR for 1-SD higher BMI predicting vascular-related dementia was 1.63 (95% CI, 1.13-2.35).
In a two-sample MR study, the OR for vascular-related dementia per 1-SD higher BMI was 1.54 (1.10-2.16) using inverse-variance weighted methods.
Systolic blood pressure mediated 18% and diastolic blood pressure mediated 25% of the genetic effect of BMI on vascular-related dementia.
Interpretation:
High BMI is associated with an increased risk of vascular-related dementia, with part of this risk being mediated through high blood pressure, indicating that both high BMI and hypertension are modifiable risk factors for dementia prevention.
Limitations:
Causality cannot be definitively established due to potential residual confounding.
The study primarily included individuals of Danish descent, which may limit generalizability and applicability to other populations.
Conclusion:
The findings support the hypothesis that elevated BMI is a causal contributor to vascular dementia, emphasizing the importance of managing both BMI and blood pressure for effective dementia prevention.
