Plasma metabolomic signature of healthy lifestyle, structural brain reserve and risk of dementia

作者：Fei Tian, Yuhua Wang, Zhengmin Qian, Shanshan Ran, Zilong Zhang, Chongjian Wang, Stephen Edward McMillin, Niraj R. Chavan, Hualiang Lin · 发表于：Brain · 年份：2024 · DOI：10.1093/brain/awae257 · 被引用次数：30 · 研究领域：Metabolomics and Mass Spectrometry Studies、Diet and metabolism studies、Nutritional Studies and Diet

Although the association between healthy lifestyle and dementia risk has been documented, the relationship between a metabolic signature indicative of healthy lifestyle and dementia risk and the mediating role of structural brain impairment remain unknown. We retrieved 136 628 dementia-free participants from UK Biobank. Elastic net regression was used to obtain a metabolic signature that represented lifestyle behaviours. Cox proportional hazard models were fitted to explore the associations of lifestyle-associated metabolic signature with incident dementia. Causal associations between identified metabolites and dementia were investigated using Mendelian randomization. Mediation analysis was also conducted to uncover the potential mechanisms involving 19 imaging-derived phenotypes (brain volume, grey matter volume, white matter volume and regional grey matter volumes). During a follow-up of 12.55 years, 1783 incident cases of all-cause dementia were identified, including 725 cases of Alzheimer's dementia and 418 cases of vascular dementia. We identified 83 metabolites that could represent healthy lifestyle behaviours using elastic net regression. The metabolic signature was associated with a lower dementia risk, and for each standard deviation increment in metabolic signature, the hazard ratio was 0.89 [95% confidence interval (CI): 0.85, 0.93] for all-cause dementia, 0.95 (95% CI: 0.88, 1.03) for Alzheimer's dementia and 0.84 (95% CI: 0.77, 0.91) for vascular dementia. Mendel...