Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1_pre-dialysis) and at 24 h after dialysis (T2_{post-dialysis}). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2_{post-dialysis} compared with that at T1_pre-dialysis. At both T1_pre-dialysis and T2_{post-dialysis}, patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)–CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF–CBF coupling at T2_{post-dialysis} than at T1_pre-dialysis. Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF–CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.