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
In brief
Semaglutide cuts 5-year dementia risk score by 26% in older adults
In a post-hoc analysis of 2,970 participants aged 65 and older with overweight or obesity and cardiovascular disease, semaglutide 2.4 mg reduced the rise in a validated proteomics dementia risk score by 26% over two years, and lowered the projected 20-year risk by about 9%. The finding shows a neuroprotective signal, but whether it translates into fewer clinical dementia cases remains to be proven.
- Journal
- Alzheimer's & dementia (Amsterdam, Netherlands) (Q1)
- Published
- 8 August 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Martí Jiménez-Mausbach, Betty M Tijms, Clare Paterson, Jan Christian Refsgaard
- PMID
- 42571323
- DOI
- 10.1002/dad2.70432
Why clinicians should know about it
- Picked for Biochemistry (medical) (paper of the day, 11 August 2026): Semaglutide reduces proteomics‑based dementia risk signature
Abstract
INTRODUCTION: 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. METHODS: In a post hoc analysis of the Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial, adults ≥ 65 years with overweight/obesity and cardiovascular disease without diabetes (n = 2970) were randomized to semaglutide 2.4 mg or placebo. Non-fasted serum samples at baseline and week 104 were analyzed using the dSST. RESULTS: 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% (β -0.44; P < 0.001). DISCUSSION: Semaglutide slowed progression of a validated proteomics-based dementia risk signature.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.