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.

中文翻译：

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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 年认知能力下降之间的关联。Doetinchem 队列研究


背景基于年龄 （MetaboAge） 和死亡率 （MetaboHealth） 的代谢组学评分被认为是整体健康的指标，但它们与普通人群认知的关联尚不清楚。因此，研究了 MetaboAge/MetaboHealth 与认知水平和认知下降之间的关联，以及男性和女性之间的差异。方法 使用了来自 Doetinchem 队列研究的 2821 名参与者 （50% 女性，年龄范围 45-75） 的数据。MetaboAge 和 MetaboHealth 是根据基线时的 1H-NMR 代谢组学数据计算的。认知领域评分 （记忆、灵活性和处理速度） 和整体认知功能在 10 年期间可用。使用线性回归研究 MetaboAge/MetaboHealth 与认知功能水平之间的关联，而对于 MetaboAge/MetaboHealth 与认知能力下降之间的关联，则使用纵向线性混合模型。根据人口统计学和生活方式因素调整分析。结果较高的 MetaboAge 表明较差的代谢组衰老，仅与男性较低的处理速度水平相关。较高的 MetaboHealth 表明免疫代谢健康状况较差，与男性和女性所有三个领域的认知功能和整体认知功能水平较低有关。仅在男性中，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的标志物，在女性中主要是脂质代谢和炎症代谢物的标志物。结论 MetaboHealth，而不是 MetaboAge，与独立于常规危险因素的认知功能相关。 个体代谢物对男性和女性认知功能的影响不同，这表明认知功能背后的性别特异性病理生理途径。