AROUND ONE IN THREE dementia cases worldwide may be linked to diseases affecting organs outside the brain, according to a large global analysis. The findings challenge the long-standing focus on neurological causes alone and highlight the importance of managing chronic peripheral diseases as part of dementia prevention strategies.
Dementia Risk Goes Beyond the Brain
Dementia is commonly associated with Alzheimer’s disease and other neurodegenerative conditions, but it can also arise from strokes, infections, head injuries, and systemic illnesses. Increasing evidence suggests that diseases affecting the liver, kidneys, heart, senses, and immune system may indirectly drive cognitive decline.
To quantify this burden, researchers conducted a systematic review and Bayesian meta-analysis examining the association between dementia and peripheral diseases across multiple organ systems.
Global Analysis of Peripheral Disease Burden
The study reviewed 202 articles published up to September 2024 and assessed 26 peripheral diseases across nine physiological systems. Sixteen conditions were found to be significantly associated with an increased risk of dementia. Using relative risk estimates, disease prevalence data from the Global Burden of Disease Study, and disease overlap patterns from the UK Biobank, researchers calculated population attributable fractions (PAFs) to estimate how much of the global dementia burden could be linked to these conditions.
One-Third of Dementia Burden Attributable to Peripheral Diseases
Globally, the 16 identified peripheral diseases were collectively associated with 33.18% of dementia cases, corresponding to approximately 18.8 million people living with dementia worldwide. This substantial contribution was consistent across sexes, age groups, sociodemographic regions, and global locations, with trends remaining relatively stable between 1990 and 2021.
Leading Peripheral Contributors to Dementia Risk
The largest contributors to dementia burden were not traditionally viewed as neurological risk factors. Periodontal disease emerged as the single largest contributor, followed by chronic liver disease, hearing loss, and vision impairment. Other significant contributors included type 2 diabetes, chronic kidney disease, osteoarthritis, stroke, ischaemic heart disease, and chronic obstructive pulmonary disease. Many of these conditions are common, treatable, and closely linked to inflammation, vascular dysfunction, and metabolic stress.
Implications for Prevention and Public Health
The findings suggest that dementia prevention may require a broader, life-course approach that includes oral health, sensory health, metabolic disease control, and cardiovascular risk reduction.
By addressing peripheral diseases earlier and more effectively, health systems may be able to reduce a substantial proportion of future dementia cases. The study underscores the need to integrate dementia prevention into chronic disease management and public health planning.
Reference
Deng Z et al. Population attributable fractions of a wide range of peripheral diseases for the burden of dementia. Nat Hum Behav. 2026;DOI:10.1038/s41562-025-02392-2.
