Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

Fluids Barriers CNS. 2022 Feb 5;19(1):11. doi: 10.1186/s12987-022-00309-z.

Abstract

Background: The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients.

Methods: Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1).

Results: Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26.

Conclusions: CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.

Keywords: Biomarkers; Idiopathic normal pressure hydrocephalus; iNPH.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Cohort Studies
  • Female
  • Gait Disorders, Neurologic* / cerebrospinal fluid
  • Gait Disorders, Neurologic* / diagnosis
  • Gait Disorders, Neurologic* / etiology
  • Gait Disorders, Neurologic* / physiopathology
  • Humans
  • Hydrocephalus, Normal Pressure* / cerebrospinal fluid
  • Hydrocephalus, Normal Pressure* / complications
  • Hydrocephalus, Normal Pressure* / diagnosis
  • Hydrocephalus, Normal Pressure* / surgery
  • Male
  • Outcome Assessment, Health Care*
  • Ventriculoperitoneal Shunt

Substances

  • Biomarkers