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

Abstract

Background:

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a frequent comorbidity in idiopathic normal pressure hydrocephalus (iNPH). The presence of AD pathology is associated with worse outcomes after a shunt procedure in iNPH. Preoperative diagnosis of AD is challenging in patients with iNPH, which involves reduced concentrations of the cerebrospinal fluid (CSF) AD biomarkers.

Objective:

Our aim was to estimate the effect size of iNPH as a factor in CSF levels of AD biomarkers and to test if correction could be used to improve diagnostic value.

Methods:

Our cohort included 222 iNPH patients with data in the Kuopio NPH registry and brain biopsy and CSF samples available. We divided the patients into groups according to AD pathology per brain biopsy. For control cohorts, we had CSF samples from cognitively healthy individuals ( n = 33) and patients with diagnosed AD and no iNPH ( n = 39).

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Results:

Levels of all investigated biomarkers differed significantly between groups, with the exception of t-Tau levels between healthy individuals and iNPH patients with AD pathology. Applying a correction factor for each biomarker (0.842*Aβ _1 - 42, 0.779*t-Tau, and 0.610*P-Tau ₁₈₁) for the effect of iNPH yielded a sensitivity of 2.4% and specificity of 100%. The ratio of P-Tau ₁₈₁ to Aβ _1 - 42 was moderately effective in aiding recognition of AD pathology in iNPH patients (sensitivity 0.79, specificity 0.76, area under the curve 0.824).

Conclusion:

Correcting for iNPH as a factor failed to improve diagnostic effectiveness, but the P-Tau ₁₈₁/Aβ _1 - 42 ratio showed some utility in the diagnosis of AD in iNPH patients.