Serum metabolic markers for α-synucleinopathies conversion in isolated REM sleep behavior disorder: a prospective...

Previous studies have suggested that metabolic alterations are involved in the pathogenesis of α-synucleinopathies. However, the metabolic changes in isolated REM sleep behavior disorder (iRBD), the prodromal stage of α-synucleinopathies, and their relationship to phenoconversion remain unexplored.

To investigate the serum metabolic markers in patients with iRBD and evaluate their association with the risk of conversion to α-synucleinopathies.

We enrolled 148 patients with video-polysomnography (vPSG)-confirmed iRBD and 142 age- and sex-matched healthy controls (HCs). 138 patients with iRBD were prospectively followed over an average duration of 3.67 years and 34 developed to α-synucleinopathies. Serum metabolic markers, including uric acid (UA), fasting blood glucose (FBG), homocysteine (Hcy), and lipid profile were measured at baseline.

Compared with HCs, patients with iRBD exhibited significantly lower serum UA (332.15 μmol/L vs. 314.73 μmol/L, p = 0.010) and FBG (6.02 mmol/L vs. 5.69 mmol/L, p = 0.008) levels. Competing-risk regression analysis revealed that lower serum UA (hazard ratio [HR] 0.992, 95% CI 0.985-0.998, p = 0.013), higher Hcy (HR 1.070, 95% CI 1.028-1.113, p = 0.001), and higher FBG (HR 1.477, 95% CI 1.081-2.017, p = 0.014) were associated with an increased risk of conversion to dementia.

Lower serum UA and FBG levels are potential risk factors for iRBD. Furthermore, distinct markers, including lower serum UA levels and elevated Hcy and FBG levels, were associated with an increased risk of dementia conversion. Our findings suggest that metabolic markers may be valuable indicators for predicting specific phenoconversion outcomes in iRBD.