Alterations in secondary bile acids in adult-onset subclinical hypothyroidism with mild cognitive impairment

Abstract

Aim: Subclinical hypothyroidism (SCH) may be associated with cognitive impairment, and disruptions in bile acid (BA) metabolism are implicated in cognitive impairment-related diseases. However, the role of BA metabolism in SCH-related mild cognitive impairment (MCI) is not well understood. This study aimed to evaluate plasma BA levels in SCH patients with and without MCI using targeted metabolomics to explore potential metabolic changes linked to cognitive impairment.

Methods: A cross-sectional observational study enrolled 38 newly diagnosed adult-onset primary SCH patients with MCI (SCH-MCI), 35 patients with normal cognition (SCH-NC), and 41 well-matched healthy controls (HCs). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Plasma BA levels were quantified using targeted metabolomics via liquid chromatography-tandem mass spectrometry. Analysis of variance was employed to identify differential BAs, while Spearman correlation analysis was used to evaluate relationships between differential BAs, thyroid function parameters and MoCA scores. Receiver operating characteristic (ROC) analysis was conducted to identify sensitive BA markers for distinguishing SCH-MCI from SCH-NC.

Results: SCH-MCI patients exhibited significantly elevated levels of allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), glycodeoxycholic acid, taurodeoxycholic acid, and the ratio of alloLCA to chenodeoxycholic acid compared to SCH-NC patients. Negative correlations were found between alloLCA, isoLCA and MoCA scores. ROC analysis indicated that alloLCA and isoLCA could differentiate SCH-MCI from SCH-NC with high diagnostic accuracy.

Conclusion: Our study suggests that altered plasma secondary BA levels in SCH-MCI are negatively associated with cognitive function, highlighting the potential role of BA metabolism in SCH-related cognitive impairment.

Keywords

Subclinical hypothyroidism / mild cognitive impairment / targeted metabolomics / bile acids

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