Objective: To investigate i) HD patterns of cortical and subcortical atrophies ii) associations between atrophy and clinical, motor and cognitive features.

Background: Huntington’s disease (HD) is characterized by a triad of motor, cognitive and neuropsychiatric symptoms. Although motor symptoms are considered as disease’s onset, recent findings support that initial cognitive, neuropsychiatric and brain structural alterations are present [1,2]. Early striatal atrophy is its pathologic hallmark, but the extent of concomitant cortical deterioration is poorly characterized [3].

Method: Nineteen HD patients were evaluated at the Movement Disorders Unit of Padua University with a motor, behavioural and complete neuropsychological evaluation. They were divided into diagnostic categories according to MDS criteria (Pre-symptomatic (pre-HD), prodromal (p-HD) and manifest (HD) [4]. Patients performed 3T-MRI (T1w, T2w) and were paired with nineteen age- and sex-matched healthy controls (HC). Voxel-based morphometry was used to detect differences in grey (GM) and white matter (WM) among groups (HD vs HC) and linear regression was used to evaluate correlation between atrophy and clinical variables.

Results: Widespread greater cortical atrophy was observed in HD vs HC, with a partial sparing of the most anterior frontal cortex. Statistically significant differences emerged between GM and WM atrophy across HD subgroups (pre-HD, p-HD and HD)(p<0.005), while no difference emerged comparing atrophy with CAG repeats. Global WM/GM scores correlated positively with the total motor score (UHDRS-TMS) and negatively with the functional scales (FAS, TCF, IS) and with the tests’ mean z-score of different cognitive domains (attention, visuospatial ability, social cognition, executive, language, memory) (p<0.005).

Conclusion: We found that the patterns of GM/WM atrophy in HD correlated with the progressive motor, cognitive and functional deterioration. Of note, all the six cognitive domains investigated were an expression of a progressive GM/WM alteration pattern, supporting the value of an extensive cognitive evaluation. Further longitudinal studies are needed to clarify the role of early cognitive and structural alterations as biomarkers.

References: [1] Ruiz-Idiago, J., Pomarol-Clotet, E., & Salvador, R. (2023). Longitudinal analysis of neuropsychiatric symptoms in a large cohort of early-moderate manifest Huntington’s disease patients. Parkinsonism & Related Disorders, 106, 105228.
[2] Pfalzer, A. C., Watson, K. H., Ciriegio, A. E., Hale, L., Diehl, S., McDonell, K. E., … & Claassen, D. O. (2023). Impairments to executive function in emerging adults with Huntington disease. Journal of Neurology, Neurosurgery & Psychiatry, 94(2), 130-135.
[3] Sampedro, F., Martínez-Horta, S., Perez-Perez, J., Horta-Barba, A., Martin-Lahoz, J., Alonso-Solís, A., … & Kulisevsky, J. (2019). Widespread increased diffusivity reveals early cortical degeneration in Huntington disease. American Journal of Neuroradiology, 40(9), 1464-1468.
[4] Reilmann, R., Leavitt, B. R., & Ross, C. A. (2014). Diagnostic criteria for Huntington’s disease based on natural history. Movement Disorders, 29(11), 1335-1341.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/regional-brain-volume-and-cognitive-alterations-in-huntingtons-disease-patients/