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.

IF 4.4 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Pub Date : 2026-08-08 eCollection Date: 2026-07-01 DOI:10.1002/dad2.70432

Martí Jiménez-Mausbach, Betty M Tijms, Clare Paterson, Jan Christian Refsgaard

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引用次数: 0

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.

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Semaglutide降低了超重或肥胖且无糖尿病心血管疾病的老年人的基于蛋白质组学的痴呆风险特征：SELECT 3期试验的事后分析

血浆蛋白质组学检测痴呆发病前的多途径生物学变化。痴呆somassignal Test （dSST）是一种经过验证的25蛋白评分，可预测5年和20年的全因痴呆风险。临床前和临床数据提示胰高血糖素样肽-1受体激动剂可能具有神经保护作用。方法：在塞马鲁肽对超重或肥胖患者心脏病和卒中影响的事后分析（SELECT）试验中，≥65岁的超重/肥胖和无糖尿病心血管疾病的成年人（n = 2970）被随机分配到塞马鲁肽2.4 mg或安慰剂组。基线和第104周的非空腹血清样本使用dSST进行分析。结果：与安慰剂相比，Semaglutide降低了预测痴呆风险的增加：5年风险增加减少2.5倍（预测事件发生率降低26.0%；比值比[OR] 0.74, 95%可信区间[CI] 0.65-0.85）， 20年风险增加减少1.67倍（OR降低8.8%;OR 0.91, 95% CI 0.88-0.94）。它还将较高痴呆风险分类的几率降低了36% （β -0.44； P）讨论：Semaglutide减缓了基于蛋白质组学的痴呆风险标志的进展。

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来源期刊

Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring Medicine-Psychiatry and Mental Health

CiteScore

7.80

自引率

7.50%

发文量

101

审稿时长

8 weeks

期刊介绍： Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.