A-114: Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus: Associations With Cognition, Gait Symptoms, and Diagnostic Cerebrospinal Fluid Removal Responsiveness

Abstract

Objective: Co-morbid Alzheimer’s disease (AD) may influence symptom expression in idiopathic normal pressure hydrocephalus (iNPH). Studies linking cerebrospinal fluid (CSF) AD biomarkers to iNPH symptoms are limited by small samples. We examined whether iNPH symptoms and post-CSF removal gait responsiveness relate to CSF AD biomarkers. Method/Data Selection: Patients with possible iNPH (n=194; Mage=75.68) underwent gait and neuropsychological assessment before and after large-volume CSF removal. Neuropsychological measures included: RBANS Digit Span, WAIS-IV Coding, FAS+Animals, Trail-Making (TMT), Hopkins Verbal Learning Test-Revised (HVLT-R), and a global neurocognitive index (GNI; average performance). Gait measures included: 10-Meter Walk Test (10MWT), Timed Up and Go (TUG)+Dual-Task (TUG-D), and Mini-Balance Evaluation Systems Test (MiniBEST). CSF amyloid beta-42 (Aβ-42), total-tau (t-tau), phosphorylated-tau (pTau181), and Aβ-42/pTau181 ratio were measured using Mayo ADEVL (ECLIA immunoassay). Controlling for age, Spearman’s correlations measured associations between biomarkers, cognition, and gait. Mann-Whitney U assessed biomarker differences between gait responders and non-responders determined by reliable change (Zchange>1.96 in ≥2 measures). Results/Data Synthesis: Aβ-42 correlated with GNI, digit span, coding, and HVLT-R learning (ρ’s=.31-.38; p’s.05) but weakly correlated (ρ=0.159-0.173; p’s<.05) with MiniBEST. Gait responders had higher Aβ-42 and lower Aβ-42/pTau ratio181 (rrbs=-.221; ps=.011). Conclusions: Aβ-42 had stronger associations with cognition than gait, while tau related modestly with gait. The presence of Aβ-42 had small associations with post-CSF removal gait responsiveness. Future work with expanded AD biomarker profiles in post-shunt follow-up may further elucidate these relationships.