Impairment of glymphatic pathway and putative meningeal lymphatic vessels in aging human

Impairment of glymphatic pathway and putative meningeal lymphatic vessels in aging human:

ABSTRACT

Objective

Aging is a major risk factor for numerous neurological disorders and the mechanisms underlying brain aging remain elusive. Recent animal studies demonstrated tight relationship between impairment of glymphatic pathway, meningeal lymphatic vessels and aging. However, the relationship in human brain remains uncertain.

Methods

In this observational cohort study, patients underwent MRI before and at multiple time points after intrathecal administration of contrast agent. Head T1‐Weighted Imaging was performed to assess function of glymphatic pathway and head high‐resolution T2‐Fluid Attenuated Inversion Recovery to visualize putative meningeal lymphatic vessels (pMLVs). We measured the signal unit ratio (SUR) of 6 locations in glymphatic pathway and pMLVs, defined percentage change in SUR from baseline to 39 hour as the clearance of glymphatic pathway and pMLVs, and then analyzed their relationships with aging.

Results

In all patients (n = 35), the SUR of glymphatic pathway and pMLVs changed significantly after intrathecal injection of contrast agent. The clearance of both glymphatic pathway and pMLVs were related to aging (all p <0.05). The clearance of pMLVs was significantly related to the clearance of the glymphatic pathway (all p <0.05), and the clearance of glymphatic pathway was significantly faster in patients with early filling of pMLVs than those with late filling (all p <0.05).

Interpretation

We revealed that both glymphatic pathway and pMLVs might be impaired in aging human brain, through the novel clinically‐available method to simultaneously visualize their clearance. Our findings also support that in humans, pMLVs are the downstream of the glymphatic pathway.

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