Glymphatic dysfunction associated with cognitive impairment in patients with unilateral intracranial atherosclerotic stenosis.

Glymphatic dysfunction, associated with cognitive impairment across various conditions, has not been extensively studied in patients with unilateral intracranial atherosclerotic stenosis (ICAS). This study aims to investigate the relationship among the severity of stenosis, glymphatic function, and cognition. We recruited 141 participants with ≥50% stenosis of unilateral intracranial internal carotid artery or M1/M2 segments of middle cerebral artery and 282 controls. All participants underwent magnetic resonance imaging along with standardized neuropsychological evaluation. Glymphatic function was assessed by the index for diffusion along the perivascular space (ALPS-index) on diffusion tensor imaging. ICAS participants had lower global cognitive score and all six cognitive domain scores compared with the controls (all P < 0.05). Of note, both ipsilateral and contralateral ALPS indices were lower in participants presenting unilateral ICAS (both P< 0.05). With the stenosis worsening, the ipsilateral ALPS-index decreased (ipsilateral: 95% CI = -0.405 to -0.092, P =0.002). A significant mediation effect of ipsilateral ALPS-index was observed between stenosis degree and global cognition (95% CI = -0.6884 to -0.0515) and executive function (95% CI = -0.8617 to -0.1082). There is a glymphatic dysfunction associated with the severity of stenosis in participants with unilateral ICAS, which may contribute to the cognitive impairment. Improving glymphatic system might be a helpful alternative therapeutic option in ICAS patients. ICAS = Intracranial atherosclerotic stenosis; CMBs = Cerebral microbleeds; CSF = Cerebrospinal fluid; CSVD = Cerebral small vessel disease; DTI-ALPS = Diffusion tensor imaging along the perivascular space; FA = Fractional anisotropy; MMSE = Mini-mental state examination; MOCA = Montreal cognitive assessment; WMHs = White matter hyperintensities.