Excess body weight may be a direct cause of vascular dementia, with elevated blood pressure playing a key role in this process, according to researchers who analyzed genetic and medical data from hundreds of thousands of people. The study was published in The Journal of Clinical Endocrinology & Metabolism (JCEM).

The link between obesity and cognitive decline has long been debated. Observational studies often produced conflicting results: some indicated an increased risk of dementia in people with excess weight during midlife, while others suggested a possible “protective effect” of higher body mass in older age. The authors of the new study explain that this paradox is related to reverse causation: in the early stages of dementia, people often lose weight, which can distort statistical analyses.

To separate cause from effect, the research team used Mendelian randomization. This method leverages inherited genetic variants that predispose individuals to higher or lower body mass index (BMI) and allows for assessment of the causal role of a factor rather than mere correlation.

The study drew on data from more than 120,000 participants in Danish population projects, as well as nearly 380,000 people from the UK Biobank. Conventional analyses again showed a U-shaped relationship: increased dementia risk appeared both in underweight and obese individuals. However, the genetic approach revealed a fundamentally different picture. The higher the genetically predicted BMI, the greater the risk of vascular dementia—without any “protective” effect of excess weight.

According to the researchers’ calculations, an increase of one standard deviation in genetically predicted BMI raised the likelihood of vascular dementia by approximately 60%. Further analysis showed that the main mechanism driving this effect is blood pressure. Systolic and diastolic pressure accounted for a substantial portion of obesity’s impact on dementia risk, while cholesterol, blood sugar, and inflammatory markers played much smaller roles.

Vascular dementia develops due to chronic impairment of blood flow to the brain, often following microstrokes. Elevated blood pressure damages vessels, depriving neurons of oxygen and nutrients. This study demonstrates that obesity, through its effect on blood pressure, initiates this cascade of changes.

The authors emphasize that these findings have important practical implications. Managing body weight and blood pressure is not only critical for overall health but also represents a real—and currently underappreciated—strategy for dementia prevention. Given the lack of effective treatments for established disease, early prevention may be key.