Altered hippocampal morphology and its association with gait impairment in idiopathic normal-pressure hydrocephalus

Background and purpose: This study aimed to characterize structural alterations of the hippocampus associated with idiopathic normal-pressure hydrocephalus (INPH), and to explore their relationship with gait disturbances in affected patients.

A total of 48 patients with INPH and 25 β-amyloid-negative healthy controls underwent MRI-based, vertex-wise three-dimensional hippocampal shape analysis. Additionally, all participants received 18F-florbetaben positron emission tomography to assess amyloid status.

Hippocampal shape analysis revealed marked bilateral deformation in the INPH group compared to controls. Both hippocampi exhibited elongation and narrowing, with the middle and posterior regions showing upward curvature, indicating vertical displacement from the hippocampal body to the tail. The normalized hippocampal volume was significantly smaller in INPH patients. No substantial volumetric or morphological differences were observed between amyloid-positive and amyloid-negative individuals within the INPH group. Notably, localized shape deformities correlated with performance on the Timed Up and Go and 10-meter walk tests, more prominently in the right hippocampus. Bilateral inward deformations at the superomedial tail and inferior body of the hippocampus were consistently linked to worse gait performance. Furthermore, smaller right normalized hippocampal volumes were negatively associated with gait test outcomes.

These findings indicate that INPH is associated with characteristic hippocampal shape abnormalities. The observed associations between hippocampal morphology and gait disturbances suggest that the hippocampus may contribute to gait and postural control in INPH.