Glymphatic dysfunction and β‐amyloid deposition in patients with idiopathic normal pressure hydrocephalus

TL;DR

This study explores how glymphatic dysfunction and beta-amyloid buildup affect cognitive decline in idiopathic normal pressure hydrocephalus patients.

Contribution

The study reveals distinct roles of glymphatic dysfunction in beta-amyloid deposition in iNPH compared to Alzheimer's disease.

Findings

iNPH patients with amyloid showed higher choroid plexus volume and worse cognitive scores.

Glymphatic dysfunction correlates with amyloid burden in iNPH but not in Alzheimer's disease patients.

Amyloid co-pathology worsens cognitive symptoms in iNPH.

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) often co‐occurs with beta‐amyloid deposition, both of which share a common pathophysiology involving glymphatic dysfunction. This study aimed to investigate the clinical impact of beta‐amyloid co‐pathology and the effects of glymphatic dysfunction on beta‐amyloid deposition in patients with iNPH.

Patients diagnosed with probable iNPH (n = 60; 28 with A+, positive amyloid PET; 32 with A‐, negative amyloid PET) and Alzheimer's disease (AD) (n = 30, A+T+N+) were enrolled from prospective cohorts at the West China Hospital of Sichuan University. All participants underwent neuropsychological tests, magnetic resonance imaging and 18F‐AV45 PET. The choroid plexus volume/estimated total intracranial volume (CPV/eTIV) and 18F‐AV45 PET standard uptake value ratio (SUVR) were calculated based on automatic segmentation to evaluate the glymphatic function and amyloid burden. ANOVA and Kruskal‐Wallis test were used for group comparison between iNPH with positive amyloid PET and other groups, and Bonferroni correction was used for post‐hoc analysis. Multivariate generalized linear models were constructed to analyze the association between CPV/eTIV and 18F‐AV45 PET SUVR in patients with iNPH and AD.

Patients with iNPH A+ exhibited the highest CPV/eTIV compared to the patients with iNPH A‐ (p = 0.006). Patients with iNPH A+ showed lower MMSE score compared to iNPH A‐ (PBon=0.013) and AD (PBon=0.039), while no significant difference was found between iNPH A‐ and AD. In iNPH patients, higher CPV/eTIV were associated with higher 18F‐AV45 PET SUVR in temporal (p = 0.007), parietal (p = 0.002), and occipital lobes (p = 0.004); however, no association was observed in patients with AD in these regions.

Our study demonstrated that beta‐amyloid co‐pathology may exacerbate the cognitive symptoms of iNPH. Moreover, glymphatic dysfunction might play a distinct role in promoting beta‐amyloid deposition in iNPH compared to Alzheimer's disease.

Figures