Individuals with cardiometabolic disease (CMD) multimorbidity have a 2.27-fold increased risk of all-cause dementia compared to those without CMD.
The risk of Alzheimer's disease is elevated by 49% in individuals with CMD multimorbidity.
Vascular dementia risk is more than 3.5 times higher in those with CMD multimorbidity.
Younger individuals (under 60) and females show stronger positive correlations between CMDs and dementia outcomes.
Neutrophils, glucose, and hemoglobin A1c are associated with mediating the relationship between CMDs and all-cause dementia.
Neutrophils account for 2.43%, while glucose and hemoglobin A1c account for 9.22% and 11.85% of the association, respectively.
Simplified
BACKGROUND: Cardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke, increase the risk of dementia. However, the correlation between CMDs and dementia in different subgroups and the underlying pathophysiological mechanisms linking CMDs with dementia warrant further investigation.
METHODS: This prospective cohort study included a total of 287,748 individuals from the UK Biobank. The outcome measures included all-cause dementia (ACD), Alzheimer's disease (AD) and vascular dementia (VD). Cox regression models and subgroup analyses were used to assess the association between CMD status and dementia, while mediation analysis was evaluated potential roles of inflammatory/metabolic markers in the observed associations.
RESULTS: Compared with those without CMD, those with CMD multimorbidity had an elevated risk of ACD ( [HR]: 2.27, 95% confidence interval [95% CI]: 1.95-2.63), AD (HR: 1.49, 95% CI: 1.13-1.97), and VD (HR: 3.70, 95% CI: 2.93-4.69). According to the subgroup analyses, the positive correlations between CMDs and ACD, as well as AD, were stronger in individuals who were under the age of 60 or female. Mediation analysis indicated that neutrophils mediated 2.43% of the association of CMDs with ACD, while glucose and hemoglobin A1c mediated 9.22% and 11.85% of the association of CMDs with ACD, respectively.
CONCLUSION: This study further expands the research on and dementia, highlighting the need for focused attention on specific populations, such as younger individuals and women. Additionally, inflammatory and metabolic biomarkers, as potential mediators, provide critical insights into the complex pathophysiological mechanisms.
Key numbers
2.27
Increase in all-cause dementia risk
for CMD multimorbidity vs. CMD-free individuals
3.70
Increase in vascular dementia risk
for CMD multimorbidity vs. CMD-free individuals
9.22%
Mediation by glucose
Percentage of mediation effect on ACD risk
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Declarations. Ethics approval and consent to participate: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). The UK biobank was approved by the Northwest Multicenter Research Ethics Committee (11/NW/0382), and all participants agreed to their inclusion, and signed written informed consent forms. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
