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Population attributable fractions of a wide range of peripheral diseases for the burden of dementia

Nature Human Behaviour (2026)Cite this article

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Abstract

Growing evidence suggests that peripheral diseases serve as risk factors for dementia, but the population-level burden of dementia associated with various peripheral diseases has remained unknown. Here, by conducting a systematic review and Bayesian meta-analyses to estimate the relative risks of 26 peripheral diseases across 9 systems with dementia, including 202 articles searched from the PubMed until 6 September 2024, we identified 16 peripheral diseases as associated with increased risk of dementia. With the relative risks estimated from meta-analyses, prevalences extracted from the Global Burden of Disease Study, and communalities among these 16 peripheral diseases derived from the UK Biobank, we analysed the population attributable fractions (PAFs) of these 16 peripheral diseases for dementia, stratified by sex, age, sociodemographic index level, world region and country, and trends from 1990 to 2021. Globally, these peripheral diseases collectively were related to a combined PAF of 33.18% (95% confidence interval (CI) 16.80–48.43) of dementia burden, corresponding to 18.8 million prevalent cases. The leading ten PAF contributors were periodontal diseases (6.10%, 95% CI 0.95–10.28), cirrhosis and other chronic liver diseases (5.51%, 95% CI 1.77–8.86), age-related and other hearing loss (4.70%, 95% CI 3.51–6.06), blindness and vision loss (4.30%, 95% CI 3.43–5.05), type 2 diabetes mellitus (3.80%, 95% CI 3.06–4.53), chronic kidney disease (2.74%, 95% CI 1.53–4.02), osteoarthritis (2.26%, 95% CI 0.41–4.12), stroke (1.01%, 95% CI 0.86–1.17), ischaemic heart disease (0.97%, 95% CI 0.69–1.29) and chronic obstructive pulmonary disease (0.92%, 95% CI 0.34–1.54). This study revealed that a series of peripheral diseases were associated with increased risk of dementia and collectively were related to about one-third of the global dementia burden, highlighting the need for targeted public health strategies.

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Fig. 1: Global prevalence and cases of dementia stratified by sex.
Fig. 2: Flowchart of study selection for the meta-analysis.
Fig. 3: RR, prevalence and PAF of 16 peripheral diseases across 9 systems.
Fig. 4: PAF, prevalence and cases of dementia related to overall peripheral diseases stratified by sex.
Fig. 5: PAF, prevalence and cases of dementia related to nine classes of peripheral diseases.
Fig. 6: Temporal trends of PAF ranking of dementia related to 16 peripheral diseases, 1990–2021.

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Data availability

The GBD 2021 is publicly available via Global Health Data Exchange at https://vizhub.healthdata.org/gbd-results/. The UK Biobank resources can be accessed through applications on their website (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). All included literature in the meta-analysis is available via PubMed at https://pubmed.ncbi.nlm.nih.gov/. The data extracted from studies included in the meta-analysis and the GBD dataset used in the study are available via Figshare at https://doi.org/10.6084/m9.figshare.30634574 (ref. 293). The UK Biobank data were used under licence and are thus not publicly available.

Code availability

The analytical methods in the study do not involve developing new computer code or algorithm that have not been previously reported. The analytical methods in the study had been described in detail in the article, with citations to the sources containing the relevant methodology and code. Accordingly, the original code required to reanalyse the data in this article is available from the corresponding author upon request.

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Acknowledgements

The data acquired from the UK Biobank in this study were under application number 70109. The UK Biobank received ethical approval from the North West Multi-Centre Research Ethics Committee (REC reference 11/NW/0382), and all participants provided written informed consent. The GBD is funded by the Bill & Melinda Gates Foundation. This work was supported by the STI 2030 Major Projects (2022ZD0211603), the National Natural Science Foundation of China (82330099, 82530100), the Key-Area Research and Development Program of Guangdong Province (2023B0303040003) and Science and Technology Program of Guangzhou (2023A03J0708) to Y.T.; the National Natural Science Foundation of China (82473563) and Guangzhou Science and Technology Programme (2024A03J0911) to Y.X.; Guangzhou Science and Technology Plan Project (2025A04J4443) and Sun Yat-sen Clinical Research Cultivating Program (SYS-Q-202208) to H.L.; and the National Natural Science Foundation of China (81872261) to S.X. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the paper.

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Author notes

  1. These authors contributed equally: Zhenhong Deng, Yuxin Yang, Queran Lin, Songhua Xiao.

Authors and Affiliations

  1. Department of Neurology, Brain Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Zhenhong Deng, Yuxin Yang, Songhua Xiao, You Zuo, Jinyuan Wang, Yongteng Xu, Honghong Li, Dongshu Xie, Qingyuan Dai, Junfeng Luo & Yamei Tang

  2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Clinical Research Design Division, Clinical Research Center, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Queran Lin & Yamei Tang

  3. WHO Collaborating Centre for Public Health Education and Training, Department of Primary Care and Public Health, School of Public Health, Faculty of Medicine, Imperial College London, London, UK

    Queran Lin

  4. Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK

    Dame Louise Robinson

  5. Division of Psychiatry, University College London, North London NHS Foundation Trust, London, UK

    Naaheed Mukadam

  6. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Yamei Tang

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Contributions

Z.D., Y.Y., Q.L. and S.X. are co-first authors. Z.D., Y.Y., Q.L. and Y.T. designed the study. Z.D., Y.Y., Q.L., S.X., Y.Z. and Y.T. accessed the data, performed the statistical analysis and verified the underlying data reported in the paper. Z.D., Y.Y., Q.L. and Y.T. drafted the initial paper. All authors critically revised the paper for important intellectual content. Y.T. supervised the study. All authors have full access to all of the data in the study and take responsibility to submit for publication. All authors have read and approved the final paper. Y.T. has the final responsibility for the decision to submit for publication.

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Correspondence to Yamei Tang.

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Nature Human Behaviour thanks Nooshin Abbasi, Christian Razo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Tables 1–25 and Figs. 1–71.

Reporting Summary

Supplementary Data 1

The detailed spatial distribution of dementia prevalence and DALYs, as well as the PAF, prevalence rates and case numbers of dementia related to overall and nine classes of peripheral diseases, across GBD regions and countries.

Supplementary Data 2

Details of the characteristics and quality assessment of all the included articles.

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Deng, Z., Yang, Y., Lin, Q. et al. Population attributable fractions of a wide range of peripheral diseases for the burden of dementia. Nat Hum Behav (2026). https://doi.org/10.1038/s41562-025-02392-2

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