Prevention & lipidsCohort study
Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes
- Prospective cohort study
- UK Biobank
Authors' conclusion
Individuals who are genetically predisposed to developing CAD also face an increased risk of developing dementia in old age. This risk is reduced in those demonstrating healthy lifestyle profiles earlier in the lifespan, particularly in those who may be at an increased risk of developing dementia caused by an underlying vascular pathology.
Study context
- Population
- UK Biobank participants free from dementia for at least 5 years after baseline8,870 all-cause dementia cases
- Participants
- 365,782 participants
- Exposure
- Higher vs lower genetic and lifestyle risk for coronary artery disease (CAD)
- Outcome
- Incident all-cause, Alzheimer's and vascular dementia
- Follow-up
- median 13.9-year follow-up
Main finding
As reported in the abstract
All-cause dementia · median 13.9 years
- Polygenic risk score (PRS)
- subhazard ratio per SD increase 1.10 (CI 1.08–1.12); P < 0.001
- Lifestyle Risk Score (LRS)
- subhazard ratio per SD increase 1.04 (CI 1.02–1.06); P = 0.006
Observational data: associations, not effects.
Secondary outcomes
| Outcome | subhazard ratio (CI) | P value |
|---|---|---|
| Vascular dementia — PRS | 1.16 (1.11–1.21) | P < 0.001 |
| Vascular dementia — LRS | 1.15 (1.09–1.22) | P < 0.001 |
| Alzheimer's disease · associations with PRS alone | 1.09 (1.06–1.13) | P < 0.001 |
| Vascular dementia, highest vs lowest tertiles of both PRS and LRS · additive rather than interactive effect | 1.71 (1.39–2.11) | P < 0.001 |
- Vascular dementia, highest vs lowest tertiles of both PRS and LRS — Low vs high LRS tertile, regardless of PRS tertile
- 30% reduction; P<0.001 for all
Neuroimaging (MRI subset)
- White matter hyperintensity volume, highest vs lowest risk tertiles
- ≈25% greater
- Little difference in gray matter or hippocampal volumes
- 32 028 participants recalled for MRI
Original publication
Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes. Circulation. Published 4 April 2025. doi:10.1161/circulationaha.124.070632
Summarised from the published abstract; every number is checked against it