One-month early time-restricted eating enhances long-term memory by modulating brain fluid dynamics in males with metabolic syndrome: Evidence from perivascular diffusion and global blood-oxygen-level-dependent-cerebrospinal fluid coupling

BackgroundMetabolic syndrome (MetS) serves as a precursor to Alzheimer's disease, a condition characterized by initial memory impairment and driven by dysregulated brain fluid dynamics. While time-restricted eating (TRE) improves memory in MetS, the mechanistic role of brain fluid dynamics in this process remains unclear.ObjectiveTo investigate whether a 1-month early TRE (eTRE) intervention enhances memory performance by improving brain fluid dynamics in individuals with MetS.MethodsTwenty-eight men with MetS and 30 matched healthy male controls underwent MRI scans. Brain fluid dynamics was assessed using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index and global blood-oxygen-level-dependent-cerebrospinal fluid (gBOLD-CSF) coupling. In the MetS group, metabolic risk factors, cognitive and psychological status, and memory performance were evaluated pre- and post-eTRE. Relationships between imaging indices and memory scores were examined by correlation analysis.ResultsAt baseline, men with MetS exhibited a lower DTI-ALPS index and higher gBOLD-CSF coupling than healthy controls (p < 0.05). After 1-month eTRE, the DTI-ALPS index increased (p < 0.001), while gBOLD-CSF coupling decreased (p = 0.027), approaching healthy control levels. Metabolic parameters and long-term memory performance also improved significantly (all p < 0.05). Changes in DTI-ALPS were positively correlated with delayed recall (r = 0.445, p < 0.05), whereas changes in gBOLD-CSF coupling were negatively correlated (r = -0.550, p < 0.05).ConclusionsA 1-month eTRE intervention improved long-term memory and brain fluid dynamics in males with MetS, providing a promising non-pharmacological strategy to counteract metabolic-driven neurodegenerative diseases.Trial registrationNational Medical Research Registration and Filing Information System (https://www.medicalresearch.org.cn/), MR-61-24-042065.