Unexpected danger of excess weight for the brain identified

Excess body weight can be a direct cause of vascular dementia development, with high blood pressure playing a key role in this process. This conclusion was reached by researchers who analyzed genetic and medical data of hundreds of thousands of people. The work is published in The Journal of Clinical Endocrinology & Metabolism (JCEM).

The connection between obesity and cognitive decline has long been controversial. Observational studies often produced contradictory results: some indicated an increased risk of dementia in overweight middle-aged people, while others suggested a possible "protective effect" of high body mass in the elderly. The authors of the new work explain that this paradox is related to reverse causality: in the early stages of dementia, people often lose weight, which can distort the statistical picture.

To separate cause from effect, a team of scientists applied the Mendelian randomization method. It uses inherited genetic variants that predispose a person to higher or lower body mass index, allowing researchers to evaluate the causal role of the factor rather than just correlation.

The study relied on data from more than 120 thousand participants in Danish population projects, as well as almost 380 thousand people from the UK Biobank. In conventional analysis, a U-shaped relationship appeared again: an increased risk of dementia was observed both in people with weight deficiency and in people with obesity.

However, the genetic approach revealed a fundamentally different picture. The higher the genetically determined body mass index, the higher the risk of vascular dementia - without any "protective" effect of excess weight.

According to the authors' calculations, an increase in genetically predicted BMI by one standard unit increased the probability of vascular dementia by approximately 60%. Additional analysis showed that the main mechanism of this influence is related to blood pressure. Systolic and diastolic pressure explained a significant portion of the effect of excess weight on dementia risk, whereas cholesterol levels, blood sugar, and inflammation markers played a much smaller role.

Vascular dementia develops due to chronic disruption of blood supply to the brain, often against the background of micro-strokes. Elevated pressure damages blood vessels, depriving neurons of oxygen and nutrients. The new study proves that obesity, through increased pressure, triggers this cascade of changes.

The authors emphasized that their findings have important practical implications. Control of body weight and blood pressure are not just factors of general health, but real and currently underestimated tools for dementia prevention. Since there are practically no effective methods for treating the already developed disease, early prevention may play a key role.