Cardiovascular disease, associated risk factors, and risk of dementia: An umbrella review of meta-analyses

Abstract

Introduction: Cardiovascular diseases (CVDs) have been associated with an increased risk of dementia; yet the evidence is mixed. This review critically appraises and synthesises current evidence exploring associations between dementia risk and CVD and their risk factors, including coronary heart disease, heart failure, atrial fibrillation, hypertension, hyperlipidaemia, and arterial stiffness.

Methods: MEDLINE, Embase, PsycINFO, and the Cochrane Database of Systematic Reviews were searched to identify systematic reviews with meta-analyses investigating the association between at least one of the CVDs of interest and dementia risk. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Systematic Reviews was used to assess methodological quality.

Results: Twenty-five meta-analyses published between 2007 and 2021 were included. Studies largely consisted of cohorts from North America and Europe. Findings were variable, with coronary heart disease, heart failure, and atrial fibrillation consistently associated with increased risk for all-cause dementia, but results were inconsistent for Alzheimer's disease. Hypertension was more frequently associated with dementia during mid-life compared to late life. Findings concerning cholesterol were complex, and while results were inconsistent for low-density lipoprotein cholesterol and total cholesterol, there appeared to be no associations between triglycerides and high-density lipoprotein cholesterol. All meta-analyses investigating hypercholesterolaemia showed significant increases in dementia risk. There was a paucity of research on the association between arterial stiffness and dementia risk.

Conclusion: Targeted CVD dementia prevention strategies could reduce dementia prevalence. Future research should determine the underpinning mechanisms linking heart and brain health to determine the most effective strategies for dementia risk reduction in CVD populations.

Keywords: cardiovascular disease; dementia; dementia risk; epidemiology; protective factor; risk factors; umbrella review.

Figure 1

Study selection flowchart.

Figure 2

Effect estimates and 95% confidence intervals of meta-analyses reporting an association between CHD and dementia, with the vertical line representing no effect. AD, Alzheimer's disease; CHD, coronary heart disease; OR, odds ratio; RR, risk ratio; VaD, vascular dementia.

Figure 3

Effect estimates of meta-analyses reporting an association between heart failure and dementia, with the vertical line representing no effect. To note, Xu et al. treated ORs as approximates to RRs, as such, violations of this assumption may have implications for the comparability of ORs and RRs, meaning that interpretation of these pooled estimates should be done cautiously. AD, Alzheimer's disease; OR, odds ratio; RR, risk ratio.

Figure 4

Effect estimates of meta-analyses reporting an association between atrial fibrillation and dementia, with the vertical line representing no effect. To note, Xu et al. treated ORs as approximates to RRs, as such, violations of this assumption may have implications for the comparability of ORs and RRs, meaning that interpretation of these pooled estimates should be done cautiously. AD, Alzheimer's disease; HR, hazard ratio; OR, odds ratio; RR, risk ratio.

Figure 5

Effect estimates of meta-analyses reporting an association between hypertension (various definitions) and dementia. The vertical line represents no effect, with distinct colours conveying age stratification. To note, Xu et al. treated ORs as approximates to RRs, as such, violations of this assumption may have implications for the comparability of ORs and RRs, meaning that interpretation of these pooled estimates should be done cautiously. AD, Alzheimer's disease; HR, hazard ratio; NR, not reported; OR, odds ratio; RR, risk ratio; VaD, vascular dementia.

Figure 6

Effect estimates of meta-analyses reporting an association between TC and dementia. The vertical line represents no effect, with different colours conveying age stratification. To note, Xu et al. treated ORs as approximates to RRs, as such, violations of this assumption may have implications for the comparability of ORs and RRs, meaning that interpretation of these pooled estimates should be done cautiously. Moreover, SMDs have been converted to approximate ORs using $OR=exp\left(\frac{\pi }{3}\times SMD\right)$. AD, Alzheimer's disease; NR, not reported; OR, odds ratio; RR, risk ratio; SMD, standard mean difference; VaD, vascular dementia.

Figure 7

Effect estimates of meta-analyses reporting an association between hypercholesterolaemia and dementia, with the vertical line representing no effect. AD, Alzheimer's disease; OR, odds ratio; RR, risk ratio.

Figure 8

Effect estimates of meta-analyses reporting an association between LDL-C and AD. The vertical line represents no effect, with different colours conveying age stratification. Note, SMDs have been converted to approximate ORs using $OR=exp\left(\frac{\pi }{3}\times SMD\right)$. AD, Alzheimer's disease; OR, odds ratio; SMD, standard mean difference.

Figure 9

Effect estimates of meta-analyses reporting an association between HDL-C and dementia. The vertical line represents no effect, with different colours conveying age stratification. To note, Xu et al. treated ORs as approximates to RRs, as such, violations of this assumption may have implications for the comparability of ORs and RRs, meaning that interpretation of these pooled estimates should be done cautiously. Moreover, SMDs have been converted to approximate ORs using $OR=exp\left(\frac{\pi }{3}\times SMD\right)$. AD, Alzheimer's disease; OR, odds ratio; RR, risk ratio; SMD, standard mean difference; VaD, vascular dementia.

Figure 10

Effect estimates of meta-analyses reporting an association between TG and dementia. The vertical line represents no effect, with different colours conveying age. Note, SMDs have been converted to approximate ORs using $OR=exp\left(\frac{\pi }{3}\times SMD\right)$. AD, Alzheimer's disease; OR, odds ratio; RR, risk ratio; SMD, standard mean difference; VaD, vascular dementia.