Preoperative Phosphorylated Tau Concentration in the Cerebrospinal Fluid Can Predict Cognitive Function Three Years after Shunt Surgery in Patients with Idiopathic Normal Pressure Hydrocephalus

Abstract

Background: Idiopathic normal pressure hydrocephalus (iNPH) is commonly treated by cerebrospinal fluid (CSF) shunting. However, the long-term efficacy of shunt intervention in the presence of comorbid Alzheimer’s disease (AD) pathology is debated.Objective: To identify AD-associated CSF biomarkers predictive of shunting surgery outcomes in patients with iNPH.Methods: Preoperative levels of total and phosphorylated Tau (p-Tau) were measured in 40 patients with iNPH divided into low (<30 pg/mL) and high (≥30 pg/mL) p-Tau groups and followed up for three years after lumboperitoneal shunting. The modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Frontal Assessment Battery, and iNPH Grading Scale scores were compared between the age-adjusted low (n = 24; mean age 75.7 years [SD 5.3]) and high (n = 11; mean age 76.0 years [SD 5.6]) p-Tau groups.Results: Cognitive function improved early in the low p-Tau group and was maintained thereafter (p = 0.005). In contrast, the high p-Tau group showed a gradual decline to baseline levels by the third postoperative year (p = 0.040). Although the p-Tau concentration did not correlate with the preoperative MMSE score, a negative correlation appeared and strengthened during follow-up (R2 = 0.352, p < 0.001). Furthermore, the low p-Tau group showed rapid and sustained mRS grade improvement, whereas mRS performance gradually declined in the high p-Tau group.Conclusions: Preoperative CSF p-Tau concentration predicted some aspects of cognitive function after shunt intervention in patients with iNPH. The therapeutic effects of shunt treatment were shorter-lasting in patients with coexisting AD pathology.

Longitudinal morphological changes during recovery from brain deformation due to idiopathic normal pressure hydrocephalus after ventriculoperitoneal shunt surgery

“…Third, a comorbidity of AD was not confirmed pathologically by brain biopsy, CSF biomarkers or amyloid imaging. Additional information could increase the diagnostic accuracy of AD comorbidity 26,27,33 , although CSF biomarkers at the spinal tap test in iNPH were fluctuate and it is difficult to determine clear cutoff values of them between pure iNPH and iNPH + AD 34 . Finally, the participants in this study did not undergo MRI at the scheduled time-point.…”

Predicting Development of Alzheimer’s Disease in Patients with Shunted Idiopathic Normal Pressure Hydrocephalus

“…Lumbar CSF levels of p-tau 181, total tau, and amyloid beta1-42 were also not significant in the analysis, and there was only a slight trend of lower amyloid beta1-42 among clinical AD group. Lumbar CSF biomarkers have been under rigorous research for iNPH shunt treatment response, but with mixed results [39,40].…”

Neuropsychological tests are useful for predicting comorbidities of idiopathic normal pressure hydrocephalus

“…24 (22)(23)(24)(25)(26) 25.5 (22.25-28) .55 23.5 (20.75-24.75) 26 (20.75-27) .42 FAB 15.5 (14-16.25) 16 (14)(15)(16)(17) . Because of the limited sample size and the absence of pathological confirmation, the results of this study need to be validated by future studies.…”

“…24 Levels of pTau above and below 30 pg/mL were used to differentiate for the presence of iNPH with AD comorbidity (Figure 1). 24…”