Dementia is a term used to describe memory loss, impaired reasoning, difficulties communicating and other mental impairments that can be caused by Alzheimer’s disease, other neurodegenerative disease, strokes, severe infections, head injuries or various other conditions. While most past studies investigating the causes and underpinnings of dementia focused on the brain, a growing body of research suggests that these mental impairments could sometimes be linked to diseases that affect other parts of the body, referred to as peripheral diseases.
Researchers at Sun Yat-sen University recently carried out a systematic review and various meta-analyses of data collected over the past decades, to explore the link between dementia and 26 different peripheral diseases, including gum diseases, liver diseases, hearing loss, type 2 diabetes and various other conditions. Their results, published in Nature Human Behavior, suggest that in approximately one-third of cases, the risk of developing dementia is linked to other diseases that do not directly affect the brain.
“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,” wrote Zhenhong Deng, Yuxin Yang and their colleagues in their paper.
“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.”
An in-depth analysis of available dementia-related data
As part of their study, the researchers analyzed data from PubMed, a publicly available medical database, which was collected as part of over 200 earlier research studies. Their analyses focused on 26 peripheral diseases and they found that 16 of these were associated with an increased risk of developing dementia.
The 16 diseases they identified were: periodontal diseases, cirrhosis and other chronic liver diseases, hearing loss, vision loss, type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), osteoarthritis, stroke, ischemic heart diseases, chronic obstructive pulmonary disease (COPD), asthma, atrial fibrillation and flutter, atopic dermatitis, rheumatoid arthritis, multiple sclerosis (MS), and inflammatory bowel disease. Deng, Yang and their colleagues estimated the proportion of overall dementia cases that could be statistically attributed to one or more of these diseases.
“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 analyzed 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,” wrote the authors.
“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 results of the team’s analyses suggest that the 16 peripheral diseases they identified could be linked to approximately one-third of total dementia cases worldwide. Notably, the five diseases that were found to be most strongly correlated with an increased risk of developing dementia included gum disease, chronic liver diseases, hearing loss, vision loss and T2DM.
“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), ischemic heart disease (0.97%, 95% CI 0.69–1.29) and chronic obstructive pulmonary disease (0.92%, 95% CI 0.34–1.54),” wrote Deng, Yang and their colleagues.
“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.”
Implications for the prevention and treatment of dementia
The results of this research team’s systematic review and meta-analyses confirm recent evidence that linked some forms of dementia to diseases that do not directly affect the brain. They also suggest that dementia is not always caused by brain injuries or diseases, which means that it might in some cases be prevented by treating other diseases early.
The researchers’ findings do not yet demonstrate a causality between the diseases they identified and a higher risk of developing dementia. Future studies could thus try to better understand how these diseases and their underlying biological processes are related to dementia.
These efforts could eventually help to shed new light on the root causes of dementia. This could in turn inform the development of new strategies for the prevention, the early detection and potentially even the treatment of some forms of dementia.
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Publication details
Zhenhong Deng et al, Population attributable fractions of a wide range of peripheral diseases for the burden of dementia, Nature Human Behaviour (2026). DOI: 10.1038/s41562-025-02392-2.
Journal information:
Nature Human Behaviour
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