Dementia risk is shaped by a mix of factors we cannot change, such as age and genetics, and factors we potentially can, including metabolic and cardiovascular health. New research from Sweden suggests those modifiable factors may influence the biological changes in the brain that underlie different forms of dementia years before symptoms appear.
In a prospective study published in The Journal of Prevention of Alzheimer’s Disease, researchers from Lund University examined how lifestyle and metabolic risk factors relate to changes in the brain associated with Alzheimer’s disease and vascular dementia. The study followed nearly 500 adults with an average age of 65 who had normal cognitive function at the start of the study and tracked biological markers in the brain over four years.
Using brain imaging and biomarker measurements, researchers assessed changes in white matter, which is commonly affected in vascular dementia, as well as levels of amyloid beta and tau, the proteins linked to Alzheimer’s disease. The goal was to understand whether different risk factors are associated with distinct disease pathways rather than dementia as a single condition.
“Much of the research available on the risk factors that we ourselves can influence does not take into account the different causes of dementia,” said Sebastian Palmqvist, PhD, senior lecturer in neurology at Lund University and senior physician at Skåne University Hospital. “This means that we have had limited knowledge of how individual risk factors affect the underlying disease mechanisms in the brain.”
The study found that several modifiable risk factors, including smoking, cardiovascular disease, high blood lipids and high blood pressure, were associated with greater damage to the brain’s blood vessels and faster accumulation of white matter changes over time. These vascular changes are a hallmark of vascular dementia and can impair blood flow and nutrient delivery within the brain.
“We saw that most modifiable risk factors — smoking, cardiovascular disease, high blood lipids and high blood pressure, among others — were linked to damage to the brain's blood vessels and a faster accumulation of so-called white matter changes,” said Isabelle Glans, doctoral student at Lund University and resident in neurology at Skåne University Hospital.
The researchers also identified metabolic factors linked to Alzheimer’s-related pathology. Diabetes was associated with greater accumulation of amyloid beta, while lower body mass index was linked to faster accumulation of tau, another protein involved in Alzheimer’s disease. The authors cautioned that these findings require further investigation and should not be interpreted as causal.
“Diabetes was associated with increased accumulation of amyloid beta, while people with lower BMI had faster accumulation of tau,” Glans said, adding that the results need to be validated in future studies.
The findings highlight the complex relationship between metabolic health, vascular function and neurodegeneration. Many people who develop dementia show evidence of both vascular and Alzheimer’s-related brain changes, rather than a single disease process. That overlap may help explain why managing metabolic and cardiovascular risk factors could matter even when Alzheimer’s pathology is present.
“Focusing on vascular and metabolic risk factors can still help reduce the combined effects of several brain changes that occur simultaneously,” Palmqvist said.
Because the study was observational, it cannot show that changing these risk factors will prevent dementia. However, the results suggest that long-term metabolic health, including blood sugar control, lipid levels and blood pressure, may influence how dementia-related changes develop in the brain over time.
For nutrition science, the study reinforces the idea that eating patterns that support metabolic and vascular health may have implications beyond heart disease or diabetes alone. Brain health appears to be closely tied to how well the body regulates blood sugar, lipids and blood flow across decades of life.
Work at the authors’ research group was supported by multiple public and nonprofit funding sources, including the National Institute on Aging, the Alzheimer’s Association, the European Research Council, the Swedish Research Council and several Swedish and international foundations. Imaging tracers and precursors were provided or sponsored by GE Healthcare, AVID Radiopharmaceuticals and Roche.