Objective: This study aimed to assess the capacity of the adapted version of the object-location memory task [1] to detect and monitor early Huntington’s Disease (HD) deficits.

Background: In the field of HD research, it is necessary to develop cognitive tasks that detect longitudinal decline to improve the predictability of treatment strategies [2]. Visuospatial memory tasks have shown promise in capturing deficits in the early manifest stages of HD, but their presence during premanifest stages remains unclear [3].

Method: At baseline 70 individuals with manifest HD, 22 with premanifest HD, and 38 controls completed the digitized object-location memory task. We also assessed the performance of 48 manifest HD participants over a 12-month period. We evaluated object-identity recognition, object-location recall, and object-location memory binding under conditions of varying cognitive load. Striatal and hippocampal volumes were calculated in 49 HD gene carriers at baseline and in 30 manifest HD participants longitudinally using FreeSurfer.

Results: At baseline, compared to controls, premanifest HD participants exhibited deficits in object location memory, while manifest HD individuals showed impairments in both in object-identity memory and object-location memory. Difficulties in binding object identity and localization contributed to localization errors in manifest HD. Localization errors were correlated with the atrophy of the putamen in HD gene carriers. HD participants reported more localization errors and more localization around distractors over one-year in high-load memory conditions. The decline in object identity was associated with increase atrophy of the caudate nucleus, whereas the decline in object localization was associated with increase atrophy of the putamen.

Conclusion: These results highlight the significance of spatial memory to the cognitive phenotype of HD [3]. Our task successfully differentiated premanifest HD from controls and performance in spatial localization are correlated with striatal volumes. Furthermore, the performance decline over time in our task, along with its correlation with the rate of atrophy, suggests its potential as a cognitive endpoint in clinical trials.

References: [1] Pertzov Y, Dong MY, Peich M-C, Husain M. 2012. Forgetting What Was Where: The Fragility of Object-Location Binding. PLOS ONE. 7:e48214.
[2] Stout JC, Andrews SC, Glikmann-Johnston Y. 2017. Cognitive assessment in Huntington disease clinical drug trials. Handb Clin Neurol. 144:227–244.
[3]Glikmann-Johnston Y, Fink KD, Deng P, Torrest A, Stout JC. 2019. Spatial memory in Huntington’s disease: A comparative review of human and animal data. Neurosci Biobehav Rev. 98:194–207.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/one-year-longitudinal-decline-in-spatial-location-memory-in-huntingtons-disease/