Association of brain glymphatic system with risk of incident mortality and morbidity

Brain glymphatic system function as measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has been associated with brain disorders, but its association with mortality and other diseases remains underexplored. This prospective study included 34,268 participants from the UK Biobank with MRI data collected since August 2014. The DTI-ALPS indices‌ of the left and right hemispheres and the average index were calculated‌. The incident mortality and morbidity were defined as the death and disease (cancer, cardiovascular, respiratory, digestive, and neurodegenerative disease) reported between the MRI collection date and December 2021. Cox proportional hazard regression analyses were used to assess the association of DTI-ALPS indices with all-cause and cause-specific mortality and morbidity. We found that a higher DTI-ALPS index, indicated better glymphatic function, was associated with reduced risks of all-cause mortality (HR, 95% CI: 0.85, 0.78–0.93; P < 0.001), cardiovascular disease (CVD)-specific mortality (HR, 95% CI: 0.77, 0.63–0.93; P = 0.01), and neurodegenerative disease-specific mortality (HR, 95% CI: 0.56, 0.37–0.84; P = 0.01). Furthermore, an elevated DTI-ALPS index was associated with reduced risks of CVD (HR, 95% CI: 0.92, 0.89–0.96; P < 0.001) and neurodegenerative disease (HR, 95% CI: 0.68, 0.58–0.80; P < 0.001). The findings deepen the understanding of the role of brain glymphatic system in health.