To explore how age and sex affect cerebrospinal fluid (CSF) dynamics, particularly examining the relationships between CSF production, meningeal lymphatic vessel (mLV) characteristics, and glymphatic function. To determine the impact of brain lymphatic function on processing speed and cognitive performance.

The glymphatic system and mLV play crucial roles in clearing waste from the brain and draining CSF. The relationship between the glymphatic system and mLVs is not fully understood. Previous research has linked glymphatic system changes to neurological disorders and systemic illnesses that feature cognitive impairment, but the mechanisms underlying such impairment remain unclear. Rodent studies suggest that impaired mLV function is associated with cognitive impairment, yet no studies have explored this relationship in humans.

We recruited 27 healthy participants from the Dallas metroplex. Various MRI scans were performed to acquire data, including T₂-FLAIR, T₁-MPRAGE, SWI, and Diffusion Tensor Imaging (DTI). mLVs along the sagittal sinus were segmented. The glymphatic system was evaluated by measuring diffusivity along the perivascular space (ie, using DTI-ALPS). Choroid plexus volumes and brain volumes were estimated. Neuropsychological tests were conducted to assess cognitive domains.

Glymphatic function decreased with age, r_s(24)=-0.62, p<0.001, while mLV (r_s(24)=0.37, p=0.06) and choroid plexus volumes (r_s(26)=0.55, p=0.003) increased. Compared to females, males had higher mLV volume (M_male=18.1cm³, M_female=12.7cm³, p=0.03), but no sex differences were observed in glymphatic function, and choroid plexus volume. We found that mLV volume increased as glymphatic function decreased (ß=-0.60, p<0.001), independent of age, and a lymphatic latent variable predicted processing speed (ß=-0.27, p=0.04), indicating that brain lymphatics play an important role in determining processing speed in humans.

With age, glymphatic function declines, which in turn leads to increases in mLV volume. These changes in the brain lymphatic system contribute to the variability in processing speed seen among healthy adults with implications for higher-order cognition.