Common dementia risk factors affect the brain through distinct vascular and Alzheimer-related pathways years before cognitive decline. Digest
Vascular and metabolic risk factors are well known to increase dementia risk, but they influence the brain through different pathological routes. To address this, researchers asked whether common risk factors could predict different types of early brain changes linked to dementia.
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The study followed 494 cognitively unimpaired adults for an average of nearly four years. Participants underwent repeated brain scans using magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI was used to measure white matter hyperintensities (WMH), bright spots on brain images that usually reflect damage to small blood vessels. PET scans were used to measure amyloid-beta and tau, proteins that build up abnormally in Alzheimer's disease. Researchers then examined how baseline demographic, genetic, clinical, lifestyle, and psychosocial factors related to longitudinal changes in these brain markers.
- Higher blood pressure, elevated blood lipids, ischemic heart disease, smoking history, and fewer years of education were each associated with a faster increase in WMH, suggesting a link to vascular health.
- Older age predicted faster progression of all three brain markers, highlighting aging as a shared driver of vascular and Alzheimer-related brain changes.
- Carrying the APOE ε4 gene variant, a well-known genetic risk factor for Alzheimer's disease, was linked to faster accumulation of amyloid-beta.
- Diabetes was associated with faster amyloid-beta buildup, pointing to a possible connection between metabolic disease and early Alzheimer's pathology.
- Lower body mass index was associated with faster tau accumulation.
- Self-reported sleep duration, alcohol intake, and living alone showed no clear links to changes in any brain marker.
These findings suggest that different biological pathways drive distinct types of brain damage years before cognitive decline becomes evident. Vascular risks such as high blood pressure and smoking likely harm the brain mainly by damaging small blood vessels, while diabetes may also interfere with how the brain clears amyloid-beta. The link between lower body weight and tau may reflect early disease-related changes in metabolism rather than a protective effect of higher weight.
Because this was an observational study, the results cannot prove cause and effect. Still, the study highlights the importance of targeting vascular and metabolic health as part of dementia prevention. In this clip, Dr. Axel Montagne discusses the potential of these emerging diagnostic tools in assessing an individual's risk of developing dementia.