‘Real-life’ hippocampal-dependent spatial memory impairments in Huntington's disease

Abstract

Hippocampal-dependent spatial memory impairments are seen in Huntington's disease animal models. Similar impairments were recently reported in Huntington's disease participants on analogous spatial memory tasks (e.g., virtual Morris Water Maze), however, these tasks do not translate well to the range of functions involved in day-to-day spatial cognition. In this study we examined ‘real-life’ hippocampal-dependent spatial memory in Huntington's disease participants. We studied premanifest Huntington's disease (N = 24), early manifest Huntington's disease (N = 14), and matched healthy controls (N = 33) with a virtual environment, which demanded spatial memory function on three levels: navigation, object location, and plan drawing. To examine the case for hippocampal-dependent spatial memory more closely, we compared the performance of our Huntington's disease participants to that of a group of temporal lobe epilepsy patients (N = 30) who were previously tested on the virtual environment. Spatial memory performance was also compared to two common neuropsychological tests of spatial cognition, the Paired Associates Learning from the Cambridge Neuropsychological Automated Test Battery, and the Rey–Osterrieth Complex Figure Test. People with early manifest Huntington's disease were impaired across all spatial memory tasks. Premanifest Huntington's disease participants were most notably impaired on the object location measure of the virtual environment, which is heavily dependent on hippocampal function, but showed no such impairments on the Paired Associates Learning or the Rey–Osterrieth Complex Figure Test. Object location memory and navigation performance did not differ between people with Huntington's disease and temporal lobe epilepsy. Aligned with studies in Huntington's disease animal models, ‘real-life’ spatial memory is impaired in people with Huntington's disease prior to clinical diagnosis. This alignment has important implications for testing treatments for Huntington's disease. From the standpoint of neurodegeneration, the dependence of our spatial memory measures on hippocampal function extends the focus of cognitive assessment research in Huntington's disease beyond its primary pathology within the striato-frontal circuit.