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

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.

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.

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).

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.