Idiopathic normal-pressure hydrocephalus, cerebrospinal fluid biomarkers, and the cerebrospinal fluid tap test

• Published in: Journal of clinical neuroscience Vol. 21; no. 8; pp. 1398 - 1403
• Main Authors: Kang, Kyunghun, Ko, Pan-Woo, Jin, Myungwon, Suk, Kyoungho, Lee, Ho-Won
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.08.2014
• Subjects: Aged; Amyloid beta-Peptides - cerebrospinal fluid; Biomarker; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - complications; Female; Gait Disorders, Neurologic - cerebrospinal fluid; Gait Disorders, Neurologic - complications; Humans; Hydrocephalus, Normal Pressure - cerebrospinal fluid; Hydrocephalus, Normal Pressure - complications; Male; Neurology; Normal pressure hydrocephalus; Peptide Fragments - cerebrospinal fluid; Phosphorylated-tau; Phosphorylation; Predictive value of tests; Psychiatric Status Rating Scales; Severity of Illness Index; Spinal Puncture - methods; tau Proteins - cerebrospinal fluid; tau Proteins - metabolism; β amyloid; Normal pressure hydrocephalus; Biomarker; Phosphorylated-tau; Cerebrospinal fluid; β amyloid; Predictive value of tests
• ISSN: 0967-5868; 1532-2653
• DOI: 10.1016/j.jocn.2013.11.039

Abstract Cerebrospinal fluid (CSF) biomarkers, including soluble amyloid β-42 (Aβ-42) and phosphorylated-tau (P-tau), reflect core pathophysiological features of Alzheimer’s disease (AD). AD is frequently a concomitant pathology in older patients with idiopathic normal-pressure hydrocephalus (iNPH), and somewhat similar altered CSF dynamics exist in both AD and iNPH. We therefore investigated relationships between lumbar CSF biomarkers Aβ-42 and P-tau and clinical parameters in iNPH patients, along with differences in these biomarkers between CSF tap test (CSFTT) responders and non-responders. Thirty-one iNPH patients (14 CSFTT responders and 17 CSFTT non-responders) were included in the final analysis. We found lower CSF Aβ-42 correlated with poor cognitive performance (r = 0.687, p < 0.001 for Korean Mini Mental State Examination; r = 0.568, p = 0.001 for Frontal Assessment Battery; r = −0.439, p = 0.014 for iNPH grading scale [iNPHGS] cognitive score; r = −0.588, p = 0.001 for Clinical Dementia Rating Scale), and lower CSF P-tau correlated with gait dysfunction (r = −0.624, p < 0.001 for Timed Up and Go Test; r = −0.652, p < 0.001 for 10 meter walking test; r = −0.578, p = 0.001 for Gait Status Scale; r = −0.543, p = 0.002 for iNPHGS gait score). In subgroup analysis, CSF P-tau/Aβ-42 ratios were significantly higher in CSFTT non-responders compared to responders ( p = 0.027). Two conjectures are suggested. One, CSF biomarkers may play different and characteristic roles in relation to different iNPH symptoms such as cognition and gait. Two, comorbid AD pathology in iNPH patients may affect the response to the CSFTT. Larger studies using combinations of other biomarkers associated with AD would be necessary to evaluate these hypotheses.