基于代谢组学的生物标志物评分与男性和女性 10 年认知能力下降的关联。多廷赫姆队列研究。
Association between metabolomics-based biomarker scores and 10-year cognitive decline in men and women. The Doetinchem Cohort Study.
机构信息
National Institute for Public Health and the Environment, Center for Prevention, Lifestyle and Health, Bilthoven, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
出版信息
Age Ageing. 2024 Nov 4;53(11). doi: 10.1093/ageing/afae256.
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.
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系尚不清楚。因此，研究了 MetaboAge/MetaboHealth 与认知水平和下降的关系，以及男女之间的差异。
方法
使用来自多廷赫姆队列研究的 2821 名参与者（女性占 50%，年龄范围为 45-75 岁）的数据。在基线时使用 1H-NMR 代谢组学数据计算 MetaboAge 和 MetaboHealth。在 10 年的时间内获得认知域评分（记忆、灵活性和处理速度）和整体认知功能。使用线性回归研究 MetaboAge/MetaboHealth 与认知功能水平的关系，使用纵向线性混合模型研究 MetaboAge/MetaboHealth 与认知下降的关系。分析调整了人口统计学和生活方式因素。
结果
较高的 MetaboAge，表明代谢组学老化较差，仅与男性的处理速度较低有关。较高的 MetaboHealth，表明免疫代谢健康状况较差，与所有三个领域的认知功能水平以及男性和女性的整体认知功能有关。仅在男性中，MetaboHealth 还与灵活性、处理速度和整体认知的 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，与认知功能有关，独立于传统的危险因素。个体代谢物对认知功能的影响在男性和女性中不同，表明认知功能的潜在病理生理途径存在性别特异性。
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