Effect of ventricular volume on cerebrospinal fluid Alzheimer's disease biomarkers in patients with idiopathic normal pressure hydrocephalus

BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a common disorder in aging populations. Alzheimer's disease (AD) is a significant comorbidity in iNPH patients, and the presence of AD pathology is associated with worse shunting outcomes. Cerebrospinal fluid (CSF) concentrations of AD-associated biomarkers in iNPH patients are universally reduced and the exact mechanism related to this is unknown.ObjectiveOur aim was to study the effects of ventricular volume on CSF AD-associated biomarker levels in iNPH patients, to determine whether a dilution effect occurs and to assess if brain AD pathology contributes to this effect.MethodsA total of 153 iNPH patients had lumbar CSF samples available for analysis, along with brain MRIs of sufficient quality. Automated image analysis software was used to determine the volume of different brain segments. Volumes normalized for age, sex and head size were used for analysis. Brain biopsy data on AD pathology was also available.ResultsNone of the intracerebral ventricular volumes correlated with CSF levels of AD-associated biomarkers, indicating no dilution effect was present in this context. However, in iNPH patients positive for amyloid-β pathology in the biopsy, the volume of the fourth ventricle correlated inversely with all investigated biomarkers.ConclusionsIntracerebral ventricular volumes do not correlate with AD biomarker levels in CSF, arguing against a dilution effect. However, in patients with AD pathology, the volume of the fourth ventricle is inversely correlated with CSF T-Tau and P-Tau₁₈₁ levels, suggesting a complex relationship between brain AD pathology, CSF flow and CSF volume in iNPH patients.