Abstract
Objectives: Aging is a major risk factor for many neurological disorders and is associated with dural lymphatic dysfunction. We sought to evaluate the association of aging with the volume of the peri-sinus lymphatic space using contrast-enhanced 3T T1-weighted black-blood magnetic resonance imaging (MRI). Methods: In this retrospective study, 165 presumed neurologically normal subjects underwent brain MRIs for cancer staging between April and November 2018. The parasagittal peri-sinus lymphatic space was evaluated using contrast-enhanced 3D T1-weighted black-blood MRIs, and volumes were measured with semiautomatic method. We compared the volumes of normalized peri-sinus lymphatic spaces between the elderly (≥65 years, n = 72) and non-elderly (n = 93) groups and performed multivariate logistic regression analyses to assess if aging is independently associated with the volume of normalized peri-sinus lymphatic spaces. Results: The normalized peri-sinus lymphatic space volume was significantly higher in the elderly than in the non-elderly (mean, 3323 ± 758.7 mL vs. 2968.7 ± 764.3 mL, p = 0.047). After adjusting the intracranial volume, age age was the strongest factor independently associated with peri-sinus lymphatic space volume (β coefficient, 28.4 (5.7–51.2), p = 0.015) followed by male sex (β coefficient, 672.4 (113.5–1230.8), p = 0.019). Conclusions: We found that the peri-sinus dural lymphatic space volume was higher in the elderly group than in the non-elderly group, and the increased peri-sinus lymphatic space was independently associated with aging. These findings indicate that the peri-sinus lymphatic space may be related with the aging process and lymphatic system dysfunction as well.
Highlights
The central nervous system has long been considered an immune-privileged organ because of its limited interactions with the immune system [1]
We found the peri-sinus lymphatic space to be significantly associated with aging even after adjusting for sex and ICV
Recent works have revealed that meningeal lymphatic vessels in the dura serve macromolecular clearing functions in the brain [4,5]
Summary
The central nervous system has long been considered an immune-privileged organ because of its limited interactions with the immune system [1]. The parenchyma of the central nervous system is devoid of lymphatic vasculature, cerebrospinal fluid (CSF) serves as a carrier of solutes and clear brain waste [2]. One of the pathways of CSF clearance is the lymphatic channels along the exiting nerves at the base of the skull [3]. The impairment of the dural lymphatic pathways has been shown to slow the paravascular efflux of amyloid-β from interstitial brain fluid, and it may represent a factor aggravating Alzheimer’s disease and age-associated cognitive decline [6]. Previous animal studies have demonstrated that advanced aging is associated with impaired glymphatic/dural lymphatic clearance [6,7]. The function of the glymphatic system is presumed to decline with age in relation to dural lymphatic dysfunction
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