Insomnia-Related Metabolomic Profiles Reflect Antioxidant Deficits and Relate to Cognitive Decline Through a...

We aimed to identify metabolites and create risk scores for insomnia symptoms in U.S. Hispanic/Latino adults.

We analyzed data from 6,107 participants in the Hispanic Community Health Study/Study of Latinos, split into discovery (n=3,932) and replication datasets (n=2,175). Serum metabolites and the Women's Health Initiative Insomnia Rating Scale (WHIIRS) were collected at baseline. We examined the relationships between 768 metabolites and insomnia symptoms and suspected insomnia (WHIIRS≥9) using the discovery dataset, followed by replication. Metabolite risk scores (MRSs) were generated with LASSO regression and evaluated for replication. We assessed the relationships of replicated metabolite measures and MRS with sleep, cognitive, and psychological traits (cross-phenotypes).

Nine metabolites were associated with insomnia symptoms in the discovery study, with two of these being replicated. Lower levels of hydrocinnamate and indolepropionate correlated with increased insomnia symptoms. We developed MRS for insomnia symptoms with replication. Various associations were observed between the two metabolites, 2 MRS, and cross-phenotypes. For instance, the WHIIRS MRS was associated with a higher risk of mild cognitive impairment (MCI) seven years later (OR:1.58, 95%CI:1.43-1.74 per 1 SD increase in MRS).

The metabolomic profile associated with insomnia symptoms encompasses diet and gut microbiome metabolites. This study identified specific metabolites linked to insomnia that are also related to comorbidities, such as a higher risk of developing MCI during follow-up, suggesting a shared mechanism.