Dementia Risk Factors Don't All Hit the Brain the Same Way

Dementia risk factors that a person can act on don’t damage the brain in the same way. A team from Lund University presented results on August 6 from tracking 494 people in the Swedish BioFINDER-2 cohort, and sorted out which risk goes with which type of brain change. High blood pressure, disordered blood fats, ischemic heart disease and smoking turned out to be linked to blood vessel damage, while diabetes and a lower body mass index were linked to the proteins associated with Alzheimer’s disease.

The estimate that around 45 percent of dementia cases are tied to modifiable factors has been circulating for years and is typically used as a single number for a single condition. Dementia, though, isn’t one disease but a group of symptoms that can arise from several different processes in the brain, and Alzheimer’s disease and vascular damage often exist together in the same person. The question the Lund researchers asked was therefore a practical one: if smoking and blood pressure carry risk, through which mechanism does that risk actually travel.

Sebastian Palmqvist, associate professor of neurology at Lund University and a physician at the Memory Clinic of Skåne University Hospital, explained in the university’s statement where the idea for the study came from.

A large share of the available research on modifiable risk factors doesn’t take into account the different causes of dementia.

The result was that individual risks were known to raise the odds of dementia, but not what exactly they were doing to brain tissue while that happened.

What was measured, and in whom

Every participant had at least two MRI scans, two PET scans for amyloid beta and two PET scans for tau protein. Average age at the start was 64.8 years, with a standard deviation of 13.3 years, and follow-up lasted 3.9 years on average. Of the total, 365 participants had no amyloid deposits in their cerebrospinal fluid, while 129 did.

The MRI scans measured changes in white matter, the nerve fibers damaged by small vessel disease, while the PET scans measured buildup of amyloid beta and tau protein. All participants were free of cognitive impairment at the start, a choice made deliberately to reduce the chance that early, still unnoticed signs of disease would themselves produce part of the measured risks. The study was published in The Journal of Prevention of Alzheimer’s Disease, 2026, volume 13, issue 2, paper number 100448.

Why blood vessels stood out, and not plaques

Because that’s where most of the measured factors clustered. Isabelle Glans, a PhD student at Lund University and a resident physician specializing in neurology, summed up the finding.

We saw that most of the modifiable risk factors were linked to blood vessel damage in the brain and to rapid accumulation of white matter changes.

The breakdown by type of change looks like this:

• high blood pressure, disordered blood fats, ischemic heart disease and smoking: faster accumulation of white matter changes
• lower education: also faster accumulation of white matter changes
• diabetes and a higher depression score: faster accumulation of amyloid beta
• lower body mass index: faster accumulation of tau protein
• carrying the APOE epsilon 4 gene: faster accumulation of both amyloid beta and tau protein

Glans also added a note on the metabolic side.

Diabetes was linked to increased accumulation of amyloid beta, while people with a lower body mass index had faster accumulation of tau protein.

She said in the same statement that both findings still need to be tested and confirmed in future research.

Body weight remains a puzzle

The link between lower body weight and tau protein sounds backward from what’s expected, and so does the earlier literature the authors cite in their introduction. Obesity in midlife raises the risk of vascular dementia, while a lower body mass index later in life is linked to a higher chance that Alzheimer’s-related test results come back positive. Whether weight loss is a cause, a consequence of early disease, or both, isn’t something a study like this one can show.

Something similar applies to depression. When the authors, in an additional analysis, accounted for whether a participant reported subjective memory decline, the link between depression score and amyloid buildup stopped being statistically significant. That’s a detail that tends to get lost in press statements, and it changes the interpretation: mild depressive symptoms in people who already notice their own memory slipping may be an early sign of the process rather than its trigger.

What this study doesn’t prove

This is an observational study, not an experiment. It shows that certain factors are linked to faster changes in the brain, but it doesn’t prove that they cause them. Data on smoking, alcohol, sleep and prior illnesses came from questionnaires at the start of follow-up, meaning from what people reported about themselves, and all the predicted effects are small once expressed on a standardized scale.

The cohort is a single one, Swedish, drawn from two hospitals, so the numbers don’t automatically carry over to other populations. An average follow-up of just under four years is short next to a process that unfolds over decades, and participants weren’t tracked through to a dementia diagnosis, only through changes on their scans. In an additional analysis limited to people who already had amyloid deposits, only lower body mass index stayed linked to tau accumulation, while age and APOE epsilon 4 carrier status were no longer significant there.

What the study does support is that managing blood pressure, blood fats, blood sugar and smoking addresses the vascular side of the problem, and that side overlaps, in most people with dementia, with Alzheimer’s changes. Palmqvist said this is why vascular health shouldn’t be written off even in people carrying a genetic risk for Alzheimer’s disease.

Focusing on vascular and metabolic risk factors can still help reduce the combined effect of multiple changes in the brain.

For now, that’s the only part of the list a patient and a doctor can act on right away, without waiting for a drug.