Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurologic condition, however, distinguishing it from other neurodegenerative aging changes remains a challenge. While CSF biomarkers of neurodegeneration have been proposed to distinguish iNPH from these confounders, existing studies have been limited and none have any long-term outcomes.  

Higher NFL, pTau181, tTau but lower Aβ1-40 are predictive of worse long-term gait outcomes after shunt surgery. NFL was proven to be the best single predictor of patient response after shunt surgery; however, the greatest potential lies in combining multiple biomarkers.  A multivariate model of NFL with pTau181, Aβ1-40 and tTau along with age and MRI Evan’s index improve predictions further (AUC 0.82[0.74-0.91]). tTau, pTau181 and Aβ1-40 were statistically different in those whose gait improved after a LVLP vs. those who did not improve. 

While pTau181, tTau and Aβ1-40 were statistically different in LVLP responder vs non-responder, they did not significantly increase the prediction provided by the MRI Evan’s index. In contrast, NFL in combination with these biomarkers, were stong predictors of long-term gait outcomes post shunt surgery. Therefore, combination of CSF biomarkers can be used in counseling patients of the expected long-term gait outcomes following surgery. This study cannot distinguish whether comorbidity or neurodegeneration, caused by iNPH itself, correlates with CSF biomarkers.