Dysfunction of cerebrospinal fluid circulation and neurovascular decoupling in end-stage renal disease patients with mild cognitive impairment

Abstract End-stage renal disease (ESRD) patients frequently experience mild cognitive impairment (MCI), which significantly affects their quality of life. Although dysfunctions in cerebrospinal fluid (CSF) circulation and neurovascular coupling (NVC) have been implicated in cognitive impairment, their interrelationship remains unclear. This study aimed to investigate the association between CSF circulation dysfunction and NVC disruption in ESRD patients with MCI. We enrolled 68 ESRD patients with MCI and 65 healthy controls (HCs). CSF circulation was assessed using choroid plexus volume (CPV), the diffusion tensor imaging along the perivascular space (DTI-ALPS) index, and perivascular space volume fraction (PVSVF). NVC was evaluated using coupling metrics between cerebral blood flow (CBF) and resting-state functional magnetic resonance imaging (MRI) indicators: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). Cognitive performance was measured using a battery of neuropsychological tests. Compared to HCs, ESRD patients showed significantly increased CPV ( P < 0.001) and enlarged PVSVF ( P < 0.05), along with a decreased DTI-ALPS index ( P < 0.01). Global and regional NVC metrics were significantly reduced in ESRD patients ( P < 0.001). Moreover, regional NVC metrics were negatively correlated with CPV. Mediation analysis further revealed that CBF-ReHo coupling in the left cingulate gyrus pregenual area 32 mediated the relationship between elevated LCPV and cognitive decline. These findings suggest that CSF circulation dysfunction and impaired NVC are interrelated in ESRD-MCI. Disruption of CSF circulation may contribute to cognitive decline by impairing NVC, highlighting both as potential targets for early diagnosis and intervention in ESRD-related cognitive impairment.