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.