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Genetic susceptibility to cardiovascular disease and risk of dementia

I K Karlsson1, A Ploner1, C Song1

  • 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Translational Psychiatry
|May 31, 2017
PubMed

Insights

Genetic predisposition to coronary artery disease (CAD) influences dementia risk following cardiovascular disease (CVD). This genetic susceptibility, not CVD itself, appears to mediate the link between CVD and dementia, likely via shared risk factors.

Area of Science:

  • Genetics
  • Neurology
  • Cardiology

Background:

  • Cardiovascular disease (CVD) is linked to dementia, but the causal relationship and role of shared risk factors remain unclear.
  • Investigating genetic predisposition may elucidate the association between CVD and dementia risk.

Purpose of the Study:

  • To determine if a genetic risk score (GRS) for coronary artery disease (CAD) directly impacts dementia risk.
  • To examine how CAD genetic susceptibility modifies the association between CVD and dementia.
  • To explore genetic overlap between CAD, Alzheimer's disease (AD), and shared risk factors.

Main Methods:

  • Utilized a Swedish twin cohort (n=13,231) to assess the effect of a CAD GRS on dementia risk post-CVD.
  • Employed summarized genome-wide association data to analyze genetic overlap between CAD and AD, and shared risk factors.
  • Calculated hazard ratios to quantify risk modifications.

Main Results:

  • A CAD GRS showed no direct effect on dementia risk (HR 0.99).
  • However, the CAD GRS significantly modified the association between CVD and dementia within 3 years of CVD diagnosis (HRs ranging from 1.59 to 1.91 across GRS quartiles).
  • No genetic overlap was found between CAD and AD, but both shared distinct genetic links with lipids.

Conclusions:

  • Genetic susceptibility to CAD modifies the association between CVD and dementia.
  • The observed link between CVD and dementia is likely mediated by shared risk factors influenced by genetic predisposition.
  • Findings suggest a complex interplay between genetic factors, cardiovascular health, and cognitive decline.

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