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Area of Science:

  • Neuroscience
  • Genetics
  • Public Health

Background:

  • Obesity is linked to vascular-related dementia, with metabolic factors as potential mediators.
  • Causality between obesity and dementia remains unclear.

Purpose of the Study:

  • To determine if high body mass index (BMI) causally increases vascular-related dementia risk.
  • To investigate if hypertension, hyperlipidemia, hyperglycemia, or inflammation mediate this effect.

Main Methods:

  • Utilized prospective cohort studies from Copenhagen and the UK, including consortia data.
  • Employed one-sample and two-sample Mendelian randomization (MR) with individual and summary-level data.
  • Assessed risk for vascular-related dementia, Alzheimer's disease, and ischemic heart disease.

Main Results:

  • One-sample MR showed a 1.63 odds ratio (OR) for vascular-related dementia per 1-SD higher BMI.
  • Two-sample MR yielded ORs ranging from 1.54 to 1.98 per 1-SD higher BMI across methods.
  • Systolic and diastolic blood pressure mediated 18% and 25% of the genetic effect of BMI on vascular-related dementia, respectively.

Conclusions:

  • High BMI is associated with increased vascular-related dementia risk, both observationally and genetically.
  • High blood pressure is a significant mediator in the relationship between BMI and vascular-related dementia.
  • Managing high BMI and blood pressure may be crucial for dementia prevention strategies.