scholarly journals Cerebrospinal Fluid Amyloid-β Oligomer Levels in Patients with Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
pp. 1-12
Author(s):  
Kaito Kawamura ◽  
Masakazu Miyajima ◽  
Madoka Nakajima ◽  
Mitsuyasu Kanai ◽  
Yumiko Motoi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Cognitive Outcome ◽  
Neurological Improvement ◽  
Csf Shunting ◽  
Before And After

Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

scholarly journals Cerebrospinal fluid levels of amyloid-beta oligomers in patients with idiopathic normal pressure hydrocephalus are elevated before shunt surgery but decrease afterward

2020 ◽  
Author(s):  
Kaito Kawamura ◽  
Masakazu Miyajima ◽  
Madoka Nakajima ◽  
Mitsuyasu Kanai ◽  
Yumiko Motoi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Beta ◽  
Normal Pressure Hydrocephalus ◽  
Characteristic Curve ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Csf Shunting ◽  
Before And After ◽  
Neurologically Normal ◽  
Aβ Oligomer

Abstract Background The amyloid-beta (Aβ) oligomer has strong neurotoxicity and is associated with cognitive impairment in Alzheimer’s disease (AD). However, its role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. We hypothesised that cerebrospinal fluid (CSF) stagnation leads to Aβ oligomer accumulation in patients with iNPH. We measured CSF Aβ oligomer levels before and after CSF shunting in patients with iNPH. Methods We evaluated two iNPH cohorts: an analysis cohort (cohort-1) with 52 patients and a validation cohort (cohort-2) with 13 patients. For comparison cohorts, we recruited 27 neurologically normal controls (NCs), 16 patients with AD, 15 patients with Parkinson’s disease (PD), and 14 patients with progressive supranuclear palsy (PSP). We measured CSF Aβ oligomer levels and assessed participants’ neurological statuses. We then compared the iNPH cohorts’ pre-shunting measurements with the comparison groups’ measurements and compared cohort-1’s measurements recorded before and after CSF shunting. Results iNPH cohort-1 had higher CSF Aβ oligomer levels than the NC, PD, and PSP cohorts. This result was validated with data from iNPH cohort-2. CSF Aβ oligomer levels differentiated iNPH cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. Aβ oligomer levels in iNPH cohort-1 decreased after CSF shunting. However, there was no correlation between Aβ oligomer levels and cognitive functions in iNPH cohort-1. Conclusion The Aβ oligomer accumulates in patients with iNPH patients but can be eliminated with CSF shunting, suggesting that CSF stagnation causes Aβ oligomer accumulation in iNPH.

scholarly journals Delayed clearance of cerebrospinal fluid tracer from choroid plexus in idiopathic normal pressure hydrocephalus

2019 ◽  
Vol 40 (9) ◽  
pp. 1849-1858 ◽  
Author(s):  
Per Kristian Eide ◽  
Lars Magnus Valnes ◽  
Are Hugo Pripp ◽  
Kent-Andre Mardal ◽  
Geir Ringstad
Keyword(s):  
Magnetic Resonance Imaging ◽  
Cerebrospinal Fluid ◽  
Magnetic Resonance ◽  
Choroid Plexus ◽  
Normal Pressure Hydrocephalus ◽  
Amyloid Β ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Resonance Imaging ◽  
Lateral Ventricles

Impaired clearance of amyloid-β from choroid plexus is one proposed mechanism behind amyloid deposition in Alzheimer's disease. The present study examined whether clearance from choroid plexus of a cerebrospinal fluid tracer, serving as a surrogate marker of a metabolic waste product, is altered in idiopathic normal pressure hydrocephalus (iNPH), one sub-type of dementia. In a prospective observational study of close to healthy individuals (reference cohort; REF) and individuals with iNPH, we performed standardized T1-weighted magnetic resonance imaging scans before and through 24 h after intrathecal administration of a cerebrospinal fluid tracer (the magnetic resonance imaging contrast agent gadobutrol). Changes in normalized T1 signal within the choroid plexus and cerebrospinal fluid of lateral ventricles were quantified using FreeSurfer. The normalized T1 signal increased to maximum within choroid plexus and cerebrospinal fluid of lateral ventricles 6–9 h after intrathecal gadobutrol in both the REF and iNPH cohorts (enrichment phase). Peak difference in normalized T1 signals between REF and iNPH individuals occurred after 24 h (clearance phase). The results gave evidence for gadobutrol resorption from cerebrospinal fluid by choroid plexus, but with delay in iNPH patients. Whether choroid plexus has a role in iNPH pathogenesis in terms of delayed clearance of amyloid-β remains to be shown.

scholarly journals Characteristics and Reversibility of Dementia in Normal Pressure Hydrocephalus

2007 ◽  
Vol 18 (3) ◽  
pp. 149-158 ◽  
Author(s):  
Priyanka Chaudhry ◽  
Siddharth Kharkar ◽  
Jennifer Heidler-Gary ◽  
Argye E. Hillis ◽  
Melissa Newhart ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Verbal Memory ◽  
Normal Pressure ◽  
Cognitive Outcome ◽  
Shunt Surgery ◽  
Shunt Insertion ◽  
Memory Tests ◽  
Cognitive Improvement ◽  
Before And After

Studies of the cognitive outcome after shunt insertion for treatment of Normal Pressure Hydrocephalus have reported widely mixed results. We prospectively studied performance of 60 patients with Normal Pressure Hydrocephalus on a comprehensive battery of neuropsychological tests before and after shunt surgery to determine which cognitive functions improve with shunt insertion. We also administered a subset of cognitive tests before and after temporary controlled drainage of cerebrospinal fluid to determine if change on this brief subset of tests after drainage could predict which patients would show cognitive improvement three to six months after shunt insertion. There was a significant improvement in learning, retention, and delayed recall of verbal memory three to six months after surgery (using paired t-tests). The majority (74%) of patients showed significant improvement (by at least one standard deviation) on at least one of the memory tests. Absence of improvement on verbal memory after temporary drainage of cerebrospinal fluid had a high negative predictive value for improvement on memory tests at 3–6 months after surgery (96%;p= 0.0005). Also, the magnitude of improvement from Baseline to Post-Drainage on few specific tests of learning and recall significantly predicted the magnitude of improvement after shunt surgery on the same tests (r2= 0.32–0.58;p= 0.04–0.001). Results indicate that testing before and after temporary drainage may be useful in predicting which patients are less likely to improve in memory with shunting.

scholarly journals Effect of Cerebrospinal Fluid Area Mask Correction on 123I-FP-CIT SPECT Images in Idiopathic Normal Pressure Hydrocephalus

2021 ◽  
Author(s):  
Makoto Ohba ◽  
Ryota Kobayashi ◽  
Chifumi Iseki ◽  
Kazukuni Kirii ◽  
Daichi Morioka ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cerebrospinal Fluid ◽  
Normal Pressure Hydrocephalus ◽  
Specific Binding ◽  
Normal Pressure ◽  
Idiopathic Normal Pressure Hydrocephalus ◽  
Specific Binding Ratio ◽  
Volume Of Interest ◽  
Before And After ◽  
Clinical Trials Registry

Abstract Cerebrospinal fluid (CSF) mask correction has been developed to reduce the influence by CSF area dilatation for 123I-FP-CIT accumulation. In this study, we assessed the effect of CSF mask correction on the specific binding ratio (SBR) for 25 patients with idiopathic normal pressure hydrocephalus (iNPH). The SBRs with and without CSF mask correction were calculated, and changes in quantitative values were verified. Additionally, the volume removed from striatal and background (BG) volume of interest (VOI) by the CSF mask correction was calculated, the volumes removed were compared to verify their effect on SBR. Twenty and five patients had low and high SBRs, respectively, after CSF mask correction. The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively, than those in the striatal region. In conclusion, the SBR before and after CSF mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results may indicate that CSF mask correction is effective in patients with iNPH. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826.

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