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Published on: October 22, 2014
Cardiovascular diseases and risk of dementia in the general population
Jiao Luo1, Ida Juul Rasmussen1, Børge G Nordestgaard2,3,4,5
1Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
Insights
Cardiovascular diseases, particularly stroke, are likely causally linked to dementia risk. Genetic susceptibility for stroke and ischemic heart disease also increases dementia risk, highlighting the need for integrated prevention strategies.
Area of Science:
- Cardiovascular Epidemiology
- Neurodegenerative Diseases
- Genetic Epidemiology
Background:
- Observational studies suggest a link between cardiovascular diseases (CVDs) and dementia risk.
- Genetic studies have produced conflicting results regarding this association.
- Investigating causal links is crucial for effective dementia prevention.
Purpose of the Study:
- To determine if nine specific CVDs are causally associated with the risk of all-cause dementia, Alzheimer's disease, and vascular dementia.
- To leverage both observational and genetic data for robust causal inference.
Main Methods:
- Time-dependent Cox regression analyses were conducted in three large prospective cohorts (Copenhagen City Heart Study, Copenhagen General Population Study, UK Biobank).
- Individual participant data were meta-analyzed.
- Genetic susceptibility for CVDs and dementia risk were assessed using UK Biobank data and FinnGen study summary statistics.
Main Results:
- Observationally, CVDs showed significant associations with all dementia outcomes.
- Genetically, susceptibility to ischemic stroke was linked to increased risk of all-cause dementia, Alzheimer's disease, and vascular dementia.
- Genetic susceptibility for ischemic heart disease was associated with vascular dementia risk.
Conclusions:
- The association between stroke and dementia (all-cause, Alzheimer's, vascular) is likely causal.
- Genetic predisposition to ischemic heart disease is a risk factor for vascular dementia.
- Integrating cardiovascular disease prevention into dementia prevention strategies is essential.
Aims:
Cardiovascular diseases (CVDs) have been linked to increased risk of dementia in observational studies, whereas genetic studies have yielded inconsistent findings. We aimed to determine whether nine CVDs are causally associated with the risk of all-cause dementia, Alzheimer's disease, and vascular dementia.
Methods:
We performed time-dependent Cox regression analyses in three prospective cohorts, the Copenhagen City Heart Study (N=10,373), the Copenhagen General Population Study (N=101,582), and the UK Biobank (N=377,706), and meta-analyzed individual estimates. Furthermore, we assessed genetic susceptibility for CVDs and the risk of dementia using individual-level data from the UK Biobank and summary statistics from the FinnGen study.
Results:
Observationally, CVDs were associated with risk of all incident outcomes in meta-analyses, with hazard ratios up to 7.00 (95% confidence interval [CI]: 6.20, 7.92). Genetically, in the UK Biobank, susceptibility for ischemic stroke was associated with risk of all-cause dementia, Alzheimer's disease, and vascular dementia, and odds ratios (ORs) were 1.64 (1.35, 1.98), 1.44 (1.10, 1.89), and 2.06 (1.41, 3.01), respectively, with similar estimates for ischemic stroke; genetic susceptibility for ischemic heart disease was associated with risk of vascular dementia (OR: 1.24 [1.03, 1.50]). Genetic summary statistics from the FinnGen study confirmed the associations between ischemic stroke and stroke.
Conclusion:
Associations between stroke and all-cause dementia and its major subtypes are likely to be causal. Moreover, genetic susceptibility for ischemic heart disease is associated with incident vascular dementia. These findings underscore the importance of integrating CVD prevention into interventions to enable early prevention and reduce the risk of dementia.
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