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bioRxiv · 10.64898/2026.04.05.716121

The Role of Meningeal Lymphatic Vessels and Perivascular Cerebrospinal Fluid Flow in Age-Related Processing Speed Decline

Andreo, M. N.·Sivakolundu, D. K.·Zuppichini, M.·West, K.·Spence, J.·Gauthier, S.·Nguyen, T.·Rypma, B.
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Abstract

Meningeal lymphatic vessels (mLV) play essential roles in draining cerebrospinal fluid (CSF) into peripheral blood. The mLVs are hypothesized to be supportive structures to the glymphatic system, which is thought to remove metabolic byproducts from brain parenchyma and has been most directly studied in rodent models. Previous rodent studies have indicated a correlation between mLV function and cognitive performance, but this relationship in humans remains unexplored. Age-related declines in glymphatic system efficiency in humans and cognitive performance have been observed separately. This study investigates age- and sex-related differences in CSF production via choroid plexus volumes, mLV characteristics, and glymphatic system efficiency, overall elucidating the implication of cerebral lymphatic function on cognition. We recruited 26 healthy adults from Dallas-Fort Worth and acquired magnetic resonance images. mLVs along the sagittal sinus were visualized and segmented from T2-FLAIR images. The glymphatic system was evaluated by measuring diffusivity along the perivascular space. Choroid plexus volume and brain volume were estimated from T1-MPRAGE. Neuropsychological tests were conducted to assess cognitive function. Our findings indicate that glymphatic function diminishes with age, while mLV and choroid plexus volumes increase. Males displayed greater mLV volume than females, yet no sex differences were found in glymphatic function or choroid plexus volume. Notably, mLV volume increased as glymphatic function declined, independent of age. Moreover, a glymphatic-mLV latent variable significantly predicted processing speed, underscoring the influence of cerebral lymphatics on cognition. In conclusion, this study highlights a decline in glymphatic function with age, accompanied by increased mLV volumes and altered processing speed. These lymphatic system changes may underlie or contribute to the cognitive declines observed in healthy and pathological aging. Significance StatementThe glymphatic system and meningeal lymphatic vessels play crucial roles in removing brain cell waste. The relationship between these systems and their effect on human cognition, particularly processing speed, is unknown. We demonstrate that these systems change with advancing age. Variations in cerebral lymphatic function contribute to differences in processing speed independent of age, ultimately affecting higher-order cognitive function. The findings presented have implications for cognitive function in both healthy and diseased states.

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Andreo, M. N., Sivakolundu, D. K., Zuppichini, M., West, K., Spence, J., Gauthier, S., Nguyen, T., Rypma, B.. 2026-04-07. The Role of Meningeal Lymphatic Vessels and Perivascular Cerebrospinal Fluid Flow in Age-Related Processing Speed Decline. https://doi.org/10.64898/2026.04.05.716121

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