One-month early time-restricted eating enhances cognition via white matter–cortical pathways in males with metabolic syndrome: evidence from TBSS and SBM analyses

Background Metabolic syndrome (MetS) is associated with white and gray matter structural abnormalities and cognitive decline, particularly in executive function and memory. Early time-restricted eating (eTRE) is a promising lifestyle intervention to improve metabolic and cognitive health, yet its effects on brain structure remain unclear. Objective To investigate whether a 1-month eTRE intervention improves metabolic health, brain structure, and cognition in male MetS patients. Methods Twenty-one males with MetS underwent a 1-month eTRE intervention. Diffusion tensor imaging (DTI), T1-weighted images, metabolic and cognitive measures including the Trail Making Test (TMT), Processing Speed (PS), and Rey Auditory Verbal Learning Test (RAVLT) were collected at baseline and post-intervention. White matter microstructure was analyzed using tract-based spatial statistics (TBSS), and cortical morphology was assessed using surface-based morphometry (SBM). Mediation analysis explored links between cognitive and structural changes. Results After 1-month eTRE, body weight, BMI, fasting glucose, fasting insulin, and HOMA-IR significantly decreased, while QUICKI increased (all p < 0.01). Cognitive performance improved in memory, PS, and executive function. TBSS revealed fractional anisotropy (FA) increases in the left anterior thalamic radiation (ATR_L) and bilateral corticospinal tracts. SBM showed cortical thinning in the right dorsolateral prefrontal cortex (DLPFC) associated with improved delayed recall, TMT performance and PS. Mediation analysis demonstrated that the right DLPFC thickness significantly mediated the relationship between the ATR_L FA and delayed recall (ACME = 10.07, 95% CI = 1.10–37.84, p = 0.021). Conclusion One month of eTRE was associated with metabolic improvement and coordinated changes in brain structure and cognition in males with MetS, consistent with adaptive thalamo–prefrontal network remodeling.