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• The ALPS index peaks at age 30. • The ALPS index has an age-dependent decrease in cognitively unimpaired individual. • A higher ALPS index in older people can reflect a greater cortical volume reserve. The glymphatic system is a fluid-clearance pathway that clears cerebral waste products, and its dysfunction has been associated with protein aggregation diseases such as Alzheimer's disease. To understand how the glymphatic system changes with aging, we enrolled 433 cognitive unimpaired participants (236 women and 197 men, 13–88 years) and evaluated the glymphatic function by calculating diffusion tensor imaging analysis along the perivascular space (ALPS) index and explored how the ALPS index is associated with cortical atrophy and cognitive decline in older people. We found a significant inverse correlation between ALPS index and age (ρ = −0.45, p < 0.001), with a peak value in people in their thirties. A higher ALPS index indicated a better cortical reserve in regions coincided with the default mode network. Declines in mental manipulation and short-term memory performance in the older participants were associated with a lower ALPS index and cortical atrophy in the amygdala, anterior and posterior cingulate, thalamus and middle frontal regions. Our findings highlight that the ALPS index could be used to evaluate brain reserve and cognitive reserve in older people. [ABSTRACT FROM AUTHOR]

Background: The diffusion tensor imaging analysis along the perivascular space (ALPS)‐index can be used to model the glymphatic system in vivo. Aim: This study explores putative mechanisms between prediction of ALPS‐index and cognitive outcomes in young‐onset Alzheimer's disease (YOAD) and age‐matched controls (CTLs) and analyzes whether the link was mediated by the integrity of ALPS‐index‐anchored cerebral gray matter (GM). Methods: We enrolled 130 patients with YOAD and 137 CTLs. All participants underwent three‐dimensional T1‐weighted MRI, diffusion tensor imaging and cognitive tests. We constructed GM regions correlated with the ALPS‐index in the YOAD and CTL groups. For the GM regions significantly correlated with the ALPS‐index and cognitive measures, we extracted a 4‐mm radius sphere. In the YOAD and CTL groups, we used mediator analysis to explore the ALPS‐index as predictor, GM partitions as mediators, and significant cognitive test scores as outcomes. Results: Patient group had significantly lower ALPS‐index. The ALPS‐index was associated with GM volume in the cerebellar gray, dorsolateral prefrontal, thalamus, superior frontal, amygdala and hippocampus, and these coherent regions coincided with those showing GM atrophy in the YOAD group. Mediation analysis of the YOAD group suggested that the relationships between the ALPS‐index and cognitive performance were fully mediated by the integrity of ALPS‐index coherent GM areas. Discussion: Reserved GM mediates the link between the glymphatic system and cognition. Our findings suggest that GM integrity rather than the glymphatic system could serve as a direct cognitive test scores predictor in patients with YOAD. [ABSTRACT FROM AUTHOR]