Degenerative pathologies on cortical biopsy, dopaminergic depletion, and shunt efficacy in iNPH.

INTRODUCTION: Coexisting degenerative pathologies may influence the efficacy of ventriculoperitoneal (VP) shunting in idiopathic normal pressure hydrocephalus (iNPH). METHODS: We evaluated 58 iNPH patients who underwent VP shunting with cortical biopsy assessing pathologies including amyloid beta (Aβ). Concordance between biopsy-identified Alzheimer's pathology and amyloid positron emission tomography (PET) and the influence of magnetic resonance imaging-based iNPH indices, dopamine transporter (DAT) imaging, and biopsy pathologies on postoperative outcomes were examined. RESULTS: Aβ pathology was found in 23 patients (39.7%) and showed high concordance with amyloid PET (95.2%). Although Aβ positivity was associated with poorer 1-year cognitive outcome, and cognitive improvement reached significance only in Aβ-negative patients, both Aβ-positive and Aβ-negative groups exhibited functional improvement after surgery. Lower anterior striatal DAT uptake was paradoxically associated with better postoperative outcomes, particularly in Aβ-positive individuals. DISCUSSION: Cortical biopsy provides information concordant with amyloid PET, and biopsy-confirmed Alzheimer's pathology and dopaminergic status influence shunt efficacy. VP shunting remains beneficial in iNPH even with degenerative comorbidities. HIGHLIGHTS: Cortical biopsy findings showed high concordance with amyloid PET in iNPH patients. AD pathology was linked to poorer cognitive and functional outcomes after surgery. VP shunting remained beneficial even in patients with comorbid AD pathology. Lower anterior striatal DAT uptake was paradoxically associated with better outcomes. Combined use of biopsy and DAT imaging may aid prognostication in iNPH management.