gBOLD-CSF coupling as a noninvasive predictor of cognitive recovery after shunt surgery in Idiopathic normal pressure hydrocephalus.

OBJECTIVE: To investigate global blood-oxygen-level-dependent and cerebrospinal fluid (gBOLD-CSF) coupling as a biomarker for cognitive impairment in idiopathic normal pressure hydrocephalus (iNPH) and evaluate its efficacy in predicting cognitive recovery after shunt surgery. METHODS: This prospective study enrolled 71 iNPH patients and 36 healthy controls (HC). The Mini-Mental State Examination (MMSE) and the iNPH Grading Scale (iNPHGS) were assessed by an experienced neurologist. gBOLD-CSF coupling was quantified via cross-correlation analysis of signals extracted from preprocessed rsfMRI. To evaluate the efficacy in predicting 6-month postoperative cognitive improvement, multiple regression and receiver operating characteristic (ROC), calibration, and decision-curve analyses were conducted on 51 patients with baseline cognitive impairment. Longitudinal alterations in coupling strength across 6 months were assessed in a 29-patient subset using paired t-tests. RESULTS: gBOLD-CSF coupling was significantly weaker in iNPH than controls (p < 0.001) and correlated with worse cognition. Preoperative coupling independently predicted postoperative ΔMMSE (B = - 10.92, p < 0.001). ROC analysis revealed that baseline coupling effectively distinguished cognitive responders (ΔMMSE ≥ 3) from non-responders (AUC = 0.86; LOOCV AUC = 0.83), significantly outperforming conventional markers. Longitudinal analysis showed that cognitive responders exhibited a significant restoration of coupling strength postoperatively (p < 0.001), while no significant change was observed in non-responders (p = 0.292). CONCLUSION: Weakened gBOLD-CSF coupling reflects cognitive impairment in iNPH, while its postoperative restoration parallels cognitive recovery. Preoperative coupling may represent a promising investigational biomarker for estimating cognitive outcomes after shunt surgery.