Genetic study establishes causal link between obesity and cognitive decline

People with obesity and high blood pressure may face a higher risk of dementia, according to a new study published in The Journal of Clinical Endocrinology & Metabolism.

Dementia is a growing global public health challenge, with no cure currently available. People with dementia experience a severe decline in mental abilities, like memory, thinking and reasoning.

The most common forms of dementia are Alzheimer's disease, vascular dementia and mixed dementia. Dementia is a progressive brain disease that causes nerve cell damage that worsens over time, affecting memory, language, problem-solving and behavior.

"In this study, we found high body mass index (BMI) and high blood pressure are direct causes of dementia," said study author Ruth Frikke-Schmidt, M.D., Ph.D., Professor and Chief Physician at Copenhagen University Hospital - Rigshospitalet and the University of Copenhagen in Copenhagen, Denmark. "The treatment and prevention of elevated BMI and high blood pressure represent an unexploited opportunity for dementia prevention."

The researchers analyzed data from participants in Copenhagen and the U.K. and identified a causal link between higher body weight and dementia.

The researchers were able to establish a direct causal link between high BMI and dementia because they used a so-called Mendelian randomization design that mimics a randomized controlled trial. In the Mendelian randomization study design, common genetic variants causing high BMI are used as proxies for BMI altering medications. As active drug versus placebo is randomly assigned due to the randomization process in drug trials, and as BMI-increasing genetic variants versus neutral variants are randomly assorted from parents to offspring, the effects on the disease endpoint will be clear and not affected by confounding factors.

Therefore, this strategy enabled the researchers to establish a direct causal link between high BMI and risk of dementia.

Much of this increased dementia risk appeared to be driven by high blood pressure, suggesting that preventing or treating obesity and high blood pressure could help reduce dementia risk.

This study shows that high body weight and high blood pressure are not just warning signs, but direct causes of dementia. That makes them highly actionable targets for prevention."

Ruth Frikke-Schmidt, Copenhagen University Hospital

"Weight-loss medication has recently been tested for halting cognitive decline in early phases of Alzheimer's disease, but with no beneficial effect. An open question that remains to be tested is if weight-loss medication initiated before the appearance of cognitive symptoms may be protective against dementia. Our present data would suggest that early weight-loss interventions would prevent dementia, and especially vascular-related dementia," she continued.

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