F046 Monitoring visuospatial memory decline in Huntington’s disease using the object-location task

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Background Visuospatial memory tasks have shown promise in capturing deficits in the early manifest stages of Huntington’s Disease (HD), but their presence during premanifest stages remains unclear1. Aim We assessed the validity and sensitivity of the modified Object-Location task2 (OLT) in capturing early HD deficits and their evolution over time. Methods Participants included 70 manifest HD, 22 premanifest, and 38 controls. 48 manifest HD and 36 controls were followed for one year (Repair-HD multicentre study, NCT03119246). We measured visuospatial memory performance under conditions of varying cognitive load (figure 1). Striatal and hippocampal volumes were calculated in 49 HD gene carriers at baseline and in 30 manifest HD participants longitudinally (FreeSurfer). Results Premanifest HD participants exhibited deficits in object-location memory, while manifest HD individuals showed impairments in object-identity memory, object-location memory and in binding object identity and localization (swap errors) (figure 2A). Localization errors were correlated with putamen volumes at baseline (figure 2B). Manifest HD participants reported more localization errors and more localization around distractors over one year in high-load memory conditions (figure 3). Decline in object identity was associated with increased caudate atrophy (R=0.45, p=0.02), while decline in object localization with increased putamen atrophy (R=-0.37, p=0.05). Conclusions These results highlight the significance of visuospatial memory deficits to the cognitive phenotype of HD1. Visuospatial memory tests like the OLT bridge the gap between animal models and human trials, offering a consistent and culturally unbiased framework, and enabling the evaluation of early clinical intervention from the premanifest stage. References Glikmann-Johnston Y, Fink KD, Deng P, Torrest A, Stout JC. Spatial memory in Huntington’s disease: A comparative review of human and animal data. Neurosci Biobehav Rev. 2019;98:194–207. doi:10.1016/j.neubiorev.2019.01.015. Pertzov Y, Dong MY, Peich MC, Husain M. Forgetting What Was Where: The Fragility of Object-Location Binding. PLOS ONE. 2012;7(10):e48214. doi:10.1371/journal.pone.0048214

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