Association between metabolomics-based biomarker scores and 10-year cognitive decline in men and women. The Doetinchem Cohort Study.

IF 6 2区医学 Q1 GERIATRICS & GERONTOLOGY Age and ageing Pub Date : 2024-11-04 DOI:10.1093/ageing/afae256

Annelot P Smit, Gerrie-Cor M Herber, Lieke M Kuiper, M Liset Rietman, Kirsten E J Wesenhagen, H Susan J Picavet, P Eline Slagboom, W M Monique Verschuren

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Abstract

Background: Metabolomic scores based on age (MetaboAge) and mortality (MetaboHealth) are considered indicators of overall health, but their association with cognition in the general population is unknown. Therefore, the association between MetaboAge/MetaboHealth and level and decline in cognition was studied, as were differences between men and women.

Methods: Data of 2821 participants (50% women, age range 45-75) from the Doetinchem Cohort Study was used. MetaboAge and MetaboHealth were calculated from 1H-NMR metabolomics data at baseline. Cognitive domain scores (memory, flexibility and processing speed) and global cognitive functioning were available over a 10-year period. The association between MetaboAge/MetaboHealth and level of cognitive functioning was studied using linear regressions while for the association between MetaboAge/MetaboHealth and cognitive decline longitudinal linear mixed models were used. Analyses were adjusted for demographics and lifestyle factors.

Results: Higher MetaboAge, indicating poorer metabolomic ageing, was only associated with lower levels of processing speed in men. Higher MetaboHealth, indicating poorer immune-metabolic health, was associated with lower levels of cognitive functioning for all three domains and global cognitive functioning in both men and women. Only in men, MetaboHealth was also associated with 10-year decline in flexibility, processing speed and global cognition. Metabolites that contributed to the observed associations were in men mainly markers of protein metabolism, and in women mainly markers of lipid metabolism and inflammatory metabolites.

Conclusions: MetaboHealth, not MetaboAge, was associated with cognitive functioning independent of conventional risk factors. Individual metabolites affect cognitive functioning differently in men and women, suggesting sex-specific pathophysiological pathways underlying cognitive functioning.

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基于代谢组学的生物标志物评分与男性和女性 10 年认知能力衰退之间的关系。Doetinchem队列研究。

背景：基于年龄（MetaboAge）和死亡率（MetaboHealth）的代谢组评分被认为是整体健康的指标，但它们与普通人群认知能力的关系尚不清楚。因此，我们研究了 MetaboAge/MetaboHealth 与认知水平和认知能力下降之间的关系，以及男女之间的差异：方法：研究使用了 Doetinchem 队列研究中 2821 名参与者（50% 为女性，年龄在 45-75 岁之间）的数据。根据基线时的 1H-NMR 代谢组学数据计算 MetaboAge 和 MetaboHealth。认知领域得分（记忆力、灵活性和处理速度）和整体认知功能可在 10 年内获得。MetaboAge/MetaboHealth与认知功能水平之间的关系采用线性回归法进行研究，而MetaboAge/MetaboHealth与认知功能下降之间的关系则采用纵向线性混合模型进行研究。分析对人口统计学和生活方式因素进行了调整：结果：较高的 MetaboAge（表明代谢组老化较差）仅与男性较低的处理速度水平有关。MetaboHealth值越高，表明免疫代谢健康状况越差，这与男性和女性在所有三个领域的认知功能水平以及整体认知功能水平较低有关。只有在男性中，MetaboHealth 还与灵活性、处理速度和整体认知能力的 10 年下降有关。导致观察到的关联的代谢物在男性中主要是蛋白质代谢标志物，在女性中主要是脂质代谢标志物和炎症代谢物：结论：MetaboHealth（而非 MetaboAge）与认知功能相关，不受传统风险因素的影响。单个代谢物对男性和女性认知功能的影响不同，这表明认知功能的病理生理途径具有性别特异性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Age and ageing 医学-老年医学

CiteScore

9.20

自引率

6.00%

发文量

796

审稿时长

4-8 weeks

期刊介绍： Age and Ageing is an international journal publishing refereed original articles and commissioned reviews on geriatric medicine and gerontology. Its range includes research on ageing and clinical, epidemiological, and psychological aspects of later life.