Review and trials point to broader dementia prevention beyond the brain
A review of more than 200 studies linked up to a third of dementia cases to diseases outside the brain. Trials and broader evidence also support multi-domain prevention strategies.
A systematic review of more than 200 studies found that as many as a third of all dementia cases are tied to diseases outside the brain, or nearly 19 million dementia cases globally. The findings join growing evidence that suggests there are many distinct subtypes of dementia and not all of them necessarily originate in the brain. The 2024 Lancet Commission on Dementia Prevention, Intervention and Care uses an “integrative” model of evidence that looks at RCTs, long-term observational studies, meta-analyses, natural experiments, implementation research and grey literature.
The recent global review identified as many as 16 culprits using data from all over the world. The top five peripheral diseases that most strongly correlated with increased dementia risk were gum disease, chronic liver diseases, hearing loss, vision loss, and type 2 diabetes. Slightly weaker correlations were observed for osteoarthritis, kidney disease, cardiovascular disease, chronic obstructive pulmonary disease, and immune-mediated inflammatory diseases.
The review does not prove causality; however, the authors said their findings “indicate the potential to mitigate dementia incidence by proactive prevention of peripheral diseases.” According to meta-analyses, 10 of 26 common peripheral diseases lacked a significant link to dementia risk in the current systematic review, including hypertension, obesity, high cholesterol, depression, and thyroid disease. The study was published in Nature Human Behavior.
Randomized controlled trials are still essential when testing a very specific medical question. RCTs of the Alzheimer’s drugs Lecanemab and Donanemab showed modest but meaningful slowing of decline over about 18 months, although they also showed risks like brain imaging changes linked to amyloid treatments that must be monitored.
There is randomized evidence for prevention. In the U.S. POINTER RCT, more than 2,000 older adults at higher risk for cognitive decline took part in a structured lifestyle program, and over two years the group receiving more intensive support showed greater improvement in thinking skills than the group with a lighter program. The ACHIEVE RCT found that hearing treatment slowed cognitive decline in people at higher risk for dementia, but not when all participants, including low-risk individuals, were analyzed together. The SPRINT MIND RCT demonstrated that intensive blood pressure control reduced mild cognitive impairment and suggested a possible reduction in dementia.
Environmental factors also highlight the need for a wide evidence lens. Long-term exposure to fine particulate air pollution (PM2.5) is linked to higher dementia risk and greener environments are linked with lower risk. Higher educational attainment and lifelong learning seem to build “cognitive reserve,” helping the brain cope better with disease.
The GRADE Working Group now supports combining randomized and non-randomized evidence in a structured way. GRADE Guidance 44 offers four steps: define the goal and thresholds; check whether RCTs and non-RCTs show similar effects; identify which evidence-quality factors matter most; and decide whether to combine or separate the evidence.