Cardiovascular diseases and risk of dementia in the general population

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 and results 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-analysed 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. Observationally, CVDs were associated with risk of all incident outcomes in meta-analyses, with hazard ratios up to 7.00 (95% confidence interval: 6.20, 7.92). Genetically, in the UK Biobank, susceptibility for ischaemic 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 ischaemic stroke; genetic susceptibility for ischaemic 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 ischaemic stroke and stroke.Conclusion Associations between stroke and all-cause dementia and its major subtypes are likely to be causal. Moreover, genetic susceptibility for ischaemic 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.This study used observational and genetic studies using Mendelian randomization (MR) design to triangulate the causal impact of cardiovascular disease (CVDs) on dementia.We confirmed the concordant observational association between eight CVDs and dementia using three large cohorts with similar to 0.5 million participants.Through unbiased comprehensive one- and two-sample MR analyses, we substantiate causal associations between stroke and dementia and between ischaemic heart disease and vascular dementia.