Glymphatic system dysfunction as a predictor of cognitive decline and incident dementia

linear mixed models. Cox proportional hazard models were utilized to explore the link between the index and incident dementia. Mediation assessments were carried out to identify the potential mediating effects of brain parenchymal injury on the link between the ALPS-I and cognition.ResultsThe baseline ALPS-I predicted longitudinal changes in global cognition (Montreal Cognitive Assessment), language (verbal fluency test), visuospatial perception (block design subtest of Wechsler intelligence scale), and executive function (Trail Making Test). A lower score was markedly associated with a higher incident dementia risk. Mediation analysis revealed that fractional anisotropy mediated the associations between the ALPS-I and executive function (mediation effect: 21.9%) and visuospatial perception (mediation effect: 68.8%). The white matter hyperintensity fraction was found to mediate the link between the ALPS-I and global cognition (mediation effect: 55.0%).ConclusionsThis longitudinal evidence supports a link between the ALPS-I and cognitive degeneration. Furthermore, the link is mediated by subcortical parenchymal injury.