Tian Qu, Mitchell Brendan A, Corkum Abigail E, Moaddel Ruin, Ferrucci Luigi
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21225, USA.
Laboratory of Clinical Investigation, National Institute on Aging, Baltimore, MD 21224, USA.
Metabolites. 2022 Apr 15;12(4):356. doi: 10.3390/metabo12040356.
We recently found that dual decline in memory and gait speed was consistently associated with an increased risk of dementia compared to decline in memory or gait only or no decline across six aging cohorts. The mechanisms underlying this relationship are unknown. We hypothesize that individuals who experience dual decline may have specific pathophysiological pathways to dementia which can be indicated by specific metabolomic signatures. Here, we summarize blood-based metabolites that are associated with memory and gait from existing literature and discuss their relevant pathways. A total of 39 eligible studies were included in this systematic review. Metabolites that were associated with memory and gait belonged to five shared classes: sphingolipids, fatty acids, phosphatidylcholines, amino acids, and biogenic amines. The sphingolipid metabolism pathway was found to be enriched in both memory and gait impairments. Existing data may suggest that metabolites from sphingolipids and the sphingolipid metabolism pathway are important for both memory and gait impairments. Future studies using empirical data across multiple cohorts are warranted to identify metabolomic signatures of dual decline in memory and gait and to further understand its relationship with future dementia risk.
我们最近发现，与仅记忆衰退、仅步态速度衰退或六个老年队列中无衰退相比，记忆和步态速度双重衰退始终与痴呆风险增加相关。这种关系背后的机制尚不清楚。我们假设，经历双重衰退的个体可能有特定的痴呆病理生理途径，这可以通过特定的代谢组学特征来表明。在此，我们总结了现有文献中与记忆和步态相关的血液代谢物，并讨论了它们的相关途径。本系统评价共纳入39项符合条件的研究。与记忆和步态相关的代谢物属于五个共同类别：鞘脂、脂肪酸、磷脂酰胆碱、氨基酸和生物胺。发现鞘脂代谢途径在记忆和步态障碍中均富集。现有数据可能表明，鞘脂代谢物和鞘脂代谢途径对记忆和步态障碍都很重要。有必要开展跨多个队列的实证数据的未来研究，以确定记忆和步态双重衰退的代谢组学特征，并进一步了解其与未来痴呆风险的关系。
