| Title: | Causal insights of modifiable cardiovascular risk factors for dementia risk - potential for efficient prevention and improved brain health |
| Journal: | Atherosclerosis |
| Published: | 25 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42385644/ |
| DOI: | https://doi.org/10.1016/j.atherosclerosis.2026.120824 |
Publication 20534
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Abstract
BACKGROUND: The 2024 Lancet Commission report identifies 14 modifiable risk factors that may prevent half of dementia. The causal nature of these associations remains however unclear. We aimed to establish robust causal estimates for modifiable cardiovascular risk factors and dementia, offering tangible targets for effective dementia prevention.</p>
METHODS: We selected independent variants from the largest genomic consortia to date (N = 439,214 to 3,037,499) for each modifiable risk factor and generated polygenic risk scores for participants of European ancestry in the UK Biobank (N = 408,788). We conducted univariable and multivariable linear Mendelian randomization, assessed genetic shapes by nonlinear approaches, and performed several sensitivity analyses, including sex stratification.</p>
RESULTS: Genetic predisposition to high low-density-lipoprotein cholesterol (LDL-C) (1.12, 1.01-1.23), non-high-density-lipoprotein cholesterol (1.30, 1.26-1.35), triglycerides (1.19, 1.01-1.41), body mass index (1.04, 1.02-1.07), systolic (1.14, 1.09-1.20) and diastolic (1.10, 1.02-1.19) blood pressure, type 2 diabetes (1.04, 1.00-1.09) and smoking (1.18, 1.06-1.32), were associated with increased risk of all-cause dementia, while longer education was associated with a reduced risk (0.58, 0.33-0.99). Results for Alzheimer's disease and vascular dementia were directionally similar. Moreover, genetically predicted high physical activity level was associated with low risk of Alzheimer's disease (0.58, 0.33-0.99) only. Sensitivity analyses supported the main results, and no nonlinear shapes were detected.</p>
CONCLUSION: These findings provide causal insights into modifiable cardiovascular risk factors for dementia and unfold a substantial potential for dementia prevention by timely treatment of high LDL-C, triglycerides, hypertension, and diabetes, alongside smoking cessation and maintenance of normal weight.</p>
4 Authors
- Jiao Luo
- Ida Juul Rasmussen
- Jesper Qvist Thomassen
- Ruth Frikke-Schmidt
1 Application
| Application ID | Title |
|---|---|
| 66214 | Personalized prevention of dementia - integrating lifestyle, biomarkers and genomics. |
Enabling scientific discoveries that improve human health