Researchers in Canada looked at records from 38,414 adults aged 55 and over who were seen at US Alzheimer’s research centers. For each person they counted how many of ten well-known dementia risk factors were present, including high blood pressure, diabetes, high cholesterol, depression, smoking and hearing loss. The higher the count, the more likely a brain scan showed white matter damage, small infarcts or a shrunken hippocampus, and the worse people did on tests of memory, verbal fluency and everyday function. Blood pressure, cholesterol, diabetes and alcohol misuse were tied mainly to blood-vessel damage. Depression and low education were tied most strongly to test scores.
Dementia rarely has a single cause. Most brains that fail in late life carry a mix of damage: scarring in the white matter wiring, small silent strokes, and the shrinkage of memory structures typical of Alzheimer’s disease. Yet risk factors are usually studied one at a time. A new study in GeroScience asks a question closer to how people actually age. What happens when the risks pile up?
Tamara Khudair at Carleton University in Ottawa and colleagues in Montreal analyzed records from 38,414 people aged 55 or older in the US National Alzheimer’s Coordinating Center database. The team counted how many of ten modifiable risk factors named by the 2024 Lancet Commission on dementia each person had: high blood pressure, diabetes, high cholesterol, alcohol misuse, smoking, depression, obesity, uncorrected hearing loss, uncorrected vision loss and fewer than 12 years of schooling.
The typical participant had two or three. With each additional factor, the odds of moderate or extensive white matter damage on MRI rose by 19 percent. The odds of brain infarcts rose by 18 percent and the odds of hippocampal shrinkage by 5 percent. Scores for memory, verbal fluency and daily function got worse in step. The pattern held when the factors were weighted by how much each one is estimated to contribute to dementia.
The individual factors told different stories. High blood pressure had the clearest link to blood-vessel damage, raising the odds of white matter lesions and infarcts by about two-thirds. Alcohol misuse, diabetes and high cholesterol showed a similar pattern. Depression stood apart: it went with hippocampal shrinkage and with poorer results on every thinking test. Low education showed the largest gaps in test scores. A statistical path model in 4,175 people with complete data suggested that part of the link between risk and thinking runs through visible brain injury, mostly in the hippocampus.
Some results ran backwards. People with obesity and former smokers looked slightly better on a few measures. The authors point to the sample. People with Alzheimer’s often lose weight as the disease progresses, and most of these protective-looking effects vanished when the analysis was limited to people with normal cognition.
The size of the effects matters. Each extra risk factor moved test scores by only a few hundredths of a standard deviation, a difference no individual would notice. The data come from a single point in time at research centers where more than half of participants already had cognitive impairment. So the study cannot show whether the risks came before the damage. Clinicians also rated brain changes as simply present or absent rather than measuring them. When the team used precise volume measurements in a smaller group, the link between risk count and hippocampal size was not statistically significant.
Still, the central idea fits the trial evidence. Programs that tackle several risks at once, such as Finland’s FINGER study and the US POINTER trial, have produced real but modest benefits for thinking skills. This analysis offers one reason why: the brain seems to keep a running total of risk. For doctors, simply counting a patient’s risk factors could be a quick way to spot who has the most to gain from broad prevention.
Actionable Insights
Blood pressure is the clearest target for protecting the brain’s wiring. People with high blood pressure had 68 percent higher odds of white matter damage. From the paper’s figures, that is roughly 19 in 100 people with high blood pressure versus 12 in 100 without, a gap of about 7 percentage points. A separate randomized trial (SPRINT MIND) found that tight blood pressure control lowered new cases of mild cognitive impairment by about 19 percent.
The count matters more than any single factor. Going from zero to four risk factors roughly doubles the odds of white matter damage (about 11 percent vs 20 percent) and of infarcts (about 7 percent vs 12 percent).
Keep expectations for memory realistic. Four extra risk factors matched naming about one fewer animal in a minute (about 5 percent of a typical score of 21). They also matched roughly 0.4 points on an 18-point dementia rating scale, which is below the roughly 1 point doctors consider meaningful. Statisticians call effects this size “small” (Cohen’s d of 0.1 to 0.2).
Treat depression. It was linked to hippocampal shrinkage (about 46 vs 38 in 100) and worse scores on every test, although depression can also be an early sign of dementia.
Cut back on problem drinking, control diabetes and LDL cholesterol, and correct hearing and vision problems.
Context and Source
- Paywalled Paper: Linking modifiable risk factors to vascular and neurodegenerative brain changes
- Institutions: Carleton University, Department of Psychology (Ottawa); McGill University, Department of Psychiatry, and Douglas Mental Health University Institute (Montreal)
- Country: Canada (data from the US National Alzheimer’s Coordinating Center)
- Journal: GeroScience (Springer; official journal of the American Aging Association).
- Impact evaluation: The impact score of this journal is 6.0 (2025 Journal Impact Factor; 5-year JIF 6.2), evaluated against a typical high-end range of 0 to 60+ for top general science and medicine journals, therefore this is a Medium impact journal.