Ventricular volume in relation to lumbar CSF levels of amyloid-β 1–42, tau and phosphorylated tau in iNPH, is there a dilution effect?

Abstract

Background Levels of the biomarkers amyloid-β 1–42 (Aβ42), tau and phosphorylated tau (p-tau) are decreased in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). The mechanism behind this is unknown, but one potential explanation is dilution by excessive CSF volumes. The aim of this study was to investigate the presence of a dilution effect, by studying the relationship between ventricular volume (VV) and the levels of the CSF biomarkers. Methods In this cross-sectional observational study, preoperative magnetic resonance imaging (MRI) and lumbar CSF was acquired from 136 patients with a median age of 76 years, 89 men and 47 females, selected for surgical treatment for iNPH. The CSF volume of the lateral and third ventricles was segmented on MRI and related to preoperative concentrations of Aβ42, tau and p-tau. Results In the total sample VV (Median 140.7 mL) correlated weakly (rs = − 0.17) with Aβ42 (Median 534 pg/mL), but not with tau (Median 216 pg/mL) nor p-tau (Median 31 pg/mL). In a subgroup analysis, the correlation between VV and Aβ42 was only present in the male group (rs = − 0.22, p = 0.038). Further, Aβ42 correlated positively with tau (rs = 0.30, p = 0.004) and p-tau (rs = 0.26, p = 0.012) in males but not in females. Conclusions The findings did not support a major dilution effect in iNPH, at least not in females. The only result in favor for dilution was a weak negative correlation between VV and Aβ42 but not with the other lumbar CSF biomarkers. The different results between males and females suggest that future investigations of the CSF pattern in iNPH would gain from sex-based subgroup analysis.

Volumetric effect of shunt adjustments in normal pressure hydrocephalus: a randomized, double-blind trial

“…Using the Bland-Altman method, 32 the bias and limit of agreement between SyMRI and ITK-SNAP was calculated using data from a previous study. 26 Level of significance was set at an alpha level of 0.05. Statistical analysis was performed using R (version 4.0.3, R Foundation for Statistical Computing).…”

“…Clinical assessment was performed before surgery and 1 month after surgery. As in previous studies, [24][25][26] a positive shunt response was defined as at least one of the following: 1) a 20% reduction in the time or the number of steps in at least one of the two motor function tests (Timed Up and Go [TUG] and 10-m walk); 2) 4-point increase in the MMSE; or 3) one-level improvement in the continence scale and 2-point increase in the MMSE.…”

Cerebrospinal Fluid Diagnostics of Alzheimer’s Disease in Patients with Idiopathic Normal Pressure Hydrocephalus

“…The cause of decreased CSF biomarker levels in iNPH is not yet clear, but among the plausible hypotheses is a dilution effect from the increased CSF volume. The results of one study using volumetric analysis and the association of ventricular volume with CSF AD biomarkers do not support this hypothesis, but further research in this area is needed [ 36 ]. Other reasonable hypotheses include reduced cortical metabolism, decreased clearance, or changes in CSF flow [ 20 , 21 , 22 , 37 ].…”