Older adults receiving the GLP-1 agonist semaglutide showed less worsening in a protein-based dementia forecast than those receiving placebo. Digest
The biology associated with dementia extends beyond the brain to inflammation, metabolism, and blood-vessel health. Researchers investigated whether semaglutide could alter a blood-protein pattern linked to future dementia.
Researchers analyzed stored blood samples from 2,970 adults aged 65 or older who had participated in the randomized SELECT trial. All were overweight or obese and had established cardiovascular disease, but not diabetes. Participants received weekly semaglutide injections or matched placebo alongside standard care. Blood collected at the start and after 104 weeks was assessed with a model that uses 25 proteins to estimate the likelihood of a dementia diagnosis from any cause over five and 20 years. However, this secondary analysis did not systematically assess memory, thinking, or dementia diagnoses.
- Relative to their starting values, the predicted odds of dementia within five years were 26% lower with semaglutide than placebo at week 104. Risk estimates still rose in both groups, but less with semaglutide.
- For the 20-year dementia forecast, the predicted odds at week 104 were 8.8% lower with semaglutide than placebo relative to their starting values. The difference between treatments was smaller than for the five-year forecast.
- After accounting for changes in body mass index (BMI), 72% of the treatment-associated difference in the 20-year model remained.
- Semaglutide participants had 36% lower odds of being placed in a higher predicted risk category than placebo participants at week 104.
The protein score reflects processes throughout the body, including inflammation, metabolism, and blood-vessel function, not only changes within the brain. Semaglutide could affect this wider biology and thereby alter the pattern used to predict dementia. The drug mimics GLP-1, a hormone that helps the pancreas release insulin and the brain regulate appetite. But certain cells in the heart, blood vessels, and other tissues also carry GLP-1 receptors, allowing them to respond to the same signal. These additional targets offer possible ways for semaglutide to influence the protein pattern beyond the effects of eating less and losing weight.
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A blood-protein score may help track how a treatment changes biology associated with dementia, not just estimate future risk. However, whether semaglutide's effect on the score actually reflects prevention must be tested in clinical trials designed to assess cognitive decline or dementia.