Abstract
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.