Plasma neurology-related proteins associated with cognition are modulated by lifestyle in adults.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-18 DOI:10.1016/j.ebiom.2025.105933

Hernando Joaquin Margara-Escudero, Indira Paz-Graniel, Jesús Francisco García-Gavilán, Montse Fitó, Janita Bralten, Silke Matura, Jeffrey Colm Glennon, Carmen Schiweck, Elisabet Vilella, José Manuel Santos-Lozano, Nancy Babio, Jordi Salas-Salvadó

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引用次数: 0

Abstract

Background: Cognitive decline (CD) is an age-related process exacerbated by metabolic syndrome (MetS), which may be mitigated by lifestyle interventions. Plasma biomarkers hold promise for early CD detection, but prospective evidence is limited. Therefore, we aimed to prospectively determine associations between peripheral neurology-related proteins and CD, and to assess whether the lifestyle intervention of the PREDIMED-Plus trial could modify these associations.

Methods: A 6-year observational study including 314 PREDIMED-Plus participants with overweight/obesity and MetS (mean age: 65 years, 44% women) were randomised to an intensive weight-loss intervention or a control group. At baseline and 3-year follow-up, plasma neurological and inflammatory proteins were quantified using proximity extension assay (OLINK neurology panel, n = 92), ELISA (C-reactive protein, amyloid-beta 40, phosphorylated tau 231 and adiponectin, n = 4) and Luminex (interleukin-6, n = 1). Cognitive performance was assessed at baseline, 2, 4, and 6 years. Elastic net regression identified proteins predictive of four cognitive domains, and protein composite scores of cognitive function were generated. Linear-mixed models assessed their associations with 6-year CD and tested for interactions with intervention.

Findings: Distinct baseline protein composite scores, including 18, 18, 16, and 17 proteins, were identified for global cognitive function (GCF), attention, executive function, and general cognitive function (GenCF), respectively. Of these, seven proteins (RSPO1, CD200, EDA2R, VWC2, GDNF, CD38, and ADAM23) were consistently associated across all cognitive domains. Protein composite scores of GCF and GenCF were significantly associated with 6-year CD, with PREDIMED-Plus interventions modulating these associations only for changes in GCF (P = 0·01).

Interpretation: This study identified protein signatures that are associated with CD and observed that a weight loss, energy-reduced Mediterranean diet, and physical activity may influence the relationship between these protein signatures and cognitive outcomes in older adults with MetS. However, further research is needed to confirm these findings and clarify causal relationships.

Funding: Instituto de Salud Carlos III (ISCIII) co-funded by the European Union, CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), European Union's Horizon 2020 research and innovation programme, UCD Ad Astra Programme, ICREA Academia program, Sociedad Española de Endocrinología y Nutrición (SEEN), Agència Catalana de Recerca i Universitats (AGAUR).

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成人生活方式可调节与认知相关的血浆神经学相关蛋白。

背景：认知能力下降（CD）是一种与年龄相关的代谢综合征（MetS）加剧的过程，可以通过生活方式干预来缓解。血浆生物标志物有望早期检测乳糜泻，但前瞻性证据有限。因此，我们旨在前瞻性地确定周围神经相关蛋白与CD之间的关联，并评估PREDIMED-Plus试验的生活方式干预是否可以改变这些关联。方法：一项为期6年的观察性研究，包括314名超重/肥胖和MetS的PREDIMED-Plus参与者（平均年龄：65岁，44%女性）被随机分配到强化减肥干预组或对照组。在基线和3年随访时，使用接近延伸法（OLINK神经学小组，n = 92）、ELISA （c反应蛋白、淀粉样蛋白- β 40、磷酸化tau 231和脂联素，n = 4）和Luminex（白介素-6，n = 1）对血浆神经和炎症蛋白进行量化。在基线、2年、4年和6年评估认知表现。弹性网络回归识别了四个认知域的预测蛋白，并生成了认知功能的蛋白质复合评分。线性混合模型评估了它们与6年CD的关系，并测试了与干预的相互作用。研究结果：在全球认知功能（GCF）、注意力、执行功能和一般认知功能（GenCF）中，分别确定了不同的基线蛋白质复合评分，包括18、18、16和17个蛋白质。其中，7种蛋白（RSPO1、CD200、EDA2R、VWC2、GDNF、CD38和ADAM23）与所有认知领域一致相关。GCF和GenCF的蛋白质组合评分与6年CD显著相关，PREDIMED-Plus干预仅在GCF的变化中调节这些关联（P = 0.01）。解释：本研究确定了与CD相关的蛋白质特征，并观察到体重减轻、减少能量的地中海饮食和体育活动可能会影响老年met患者这些蛋白质特征与认知结果之间的关系。然而，需要进一步的研究来证实这些发现并澄清因果关系。资助：Salud Carlos III研究所（ISCIII）由欧盟共同资助，CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN)，欧盟地平线2020研究和创新计划，UCD和Astra计划，ICREA学术计划，Sociedad Española de Endocrinología y Nutrición (SEEN), agagncia Catalana de Recerca i Universitats （AGAUR）。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.