The glymphatic system (GS) is a brain-wide pathway that assists in clearing waste and toxic proteins from the brain parenchyma. Evidences suggest that the GS may be a new target in understanding the causes of neurodegenerative diseases, white matter hyperintensity (WMH) and cognitive deficiency in healthy old adults. The present study aimed to evaluate the effects of the GS activity in normal aging. The magnetic resonance imaging (MRI) data of 157 healthy people (42 to 90 years) were acquired from the OASIS-3 database, and were divided into middle age (42 – 64 years) and old age (> 65 years) groups. The WMHs were automatically segmented. The diffusion tensor imaging -analysis along the perivascular space (DTI-ALPS) was used to assess the GS function. We then performed analysis of variance and multivariable linear regression. The results showed that, compared with the middle age group, the elders have more WMHs and lower ALPS-index. Furthermore, the multiple regression analysis showed that ALPS-index was negatively correlated with the trail making test part B (TMT-B) performance, and the WMH was positively correlated with both the TMT-A and TMT-B in the middle age group. The age was the only significant predictor for the logical memory, TMT-A and TMT-B in the old age group. The present study shows that the GS activity declines during the normal aging. The TMT performance associates with the ALPS and WMH volume in the middle ages, while the cognitive function was associated with age in the old age group. These findings contribute considerably to the understanding of the mechanisms underlying the cause of WMH, cognitive decline and the subsequent neurodegenerative diseases in old adults.

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