Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 7;25(1):2397.
doi: 10.1186/s12889-025-23352-5.

Associations of cardiometabolic multimorbidity with all-cause dementia, alzheimer's disease, and vascular dementia: a cohort study in the UK biobank

Junrun Zhang #  1 , Xiaxuan Huang #  2 , Yitong Ling  1 , Xiaomei Xie  1 , Xiuli Zeng  1 , Jun Lyu  3   4 , Li'an Huang  5
Affiliations

Associations of cardiometabolic multimorbidity with all-cause dementia, alzheimer's disease, and vascular dementia: a cohort study in the UK biobank

Junrun Zhang et al. BMC Public Health. .

Abstract

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 (hazard ratio [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 cardiometabolic multimorbidity 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.

Keywords: Cardiometabolic disease; Dementia; Inflammation; Metabolism.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Flowchart of study participants
Fig. 2
Fig. 2
The Kaplan–Meier (K-M) curves were used to assess the cumulative risk between CMDs groups and different outcomes (ACD, VD and AD)
Fig. 3
Fig. 3
Risk of Alzheimer’s disease based on cardiometabolic disease status and genetic risk
Fig. 4
Fig. 4
Subgroup analysis of associations between CMD and different outcomes (ACD, VD and AD)
Fig. 5
Fig. 5
Mediation effects of inflammation-related indicators and metabolism-related indicators on the association of CMD multimorbidity and ACD, AD, and VD. Models were adjusted for age, sex, ethnicity, education level, duration of moderate activity, BMI, hypertension, smoking, and drinking status. The gray tables represent indicators of inflammation, and the green tables represent indicators of metabolism
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Livingston G, Huntley J, Liu KY, Costafreda SG, Selbæk G, Alladi S, et al. Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet. 2024;404(10452):572–628. - PubMed
    1. Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ. Epidemiology of dementias and alzheimer’s disease. Arch Med Res. 2012;43(8):600–8. - PubMed
    1. Dove A, Shang Y, Xu W, Grande G, Laukka EJ, Fratiglioni L, et al. The impact of diabetes on cognitive impairment and its progression to dementia. Alzheimers Dement. 2021;17(11):1769–78. - PubMed
    1. Wolters FJ, Segufa RA, Darweesh SKL, Bos D, Ikram MA, Sabayan B, et al. Coronary heart disease, heart failure, and the risk of dementia: A systematic review and meta-analysis. Alzheimers Dement. 2018;14(11):1493–504. - PubMed
    1. Kuźma E, Lourida I, Moore SF, Levine DA, Ukoumunne OC, Llewellyn DJ. Stroke and dementia risk: A systematic review and meta-analysis. Alzheimers Dement. 2018;14(11):1416–26. - PMC - PubMed

LinkOut - more resources