Semaglutide attenuates a proteomics-based dementia risk signature in older adults with overweight or obesity and cardiovascular disease without diabetes: A post hoc analysis of the SELECT phase 3 trial.

内容摘要

Plasma proteomics detect multi-pathway biological changes preceding dementia onset. The Dementia SomaSignal Test (dSST) is a validated 25-protein score predicting 5- and 20-year all-cause dementia risk. Preclinical and clinical data suggest glucagon-like peptide-1 receptor agonists may have neuroprotective effects. In a post hoc analysis of the Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial, adults &#x2265; 65 years with overweight/obesity and cardiovascular disease without diabetes (n&#xa0;=&#xa0;2970) were randomized to semaglutide 2.4&#xa0;mg or placebo. Non-fasted serum samples at baseline and week 104 were analyzed using the dSST. Semaglutide reduced increases in predicted dementia risk versus placebo: 2.5-fold less increase in 5-year risk (26.0% lower predicted event rate; odds ratio [OR] 0.74, 95% confidence interval [CI] 0.65-0.85) and 1.67-fold less increase in 20-year risk (8.8% lower; OR 0.91, 95% CI 0.88-0.94). It also reduced odds of higher dementia risk classification by 36% (&#x3b2; -0.44; P&#xa0;<&#xa0;0.001). Semaglutide slowed progression of a validated proteomics-based dementia risk signature.