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Brain Age Prediction in Type II GM1 Gangliosidosis

Lewis, C. J.; Chipman, S. I.; D'Souza, P.; Johnston, J. M.; Yousef, M. H.; Gahl, W. A.; Tifft, C. J.; Acosta, M. T.

2025-04-25 neurology
10.1101/2025.04.23.25326206 medRxiv
Show abstract

GM1 gangliosidosis is an inherited, progressive, and fatal neurodegenerative lysosomal storage disorder with no approved treatment. We calculated a predicted brain ages and Brain Structures Age Gap Estimation (BSAGE) for 81 MRI scans from 41 Type II GM1 gangliosidosis patients and 897 MRI scans from 556 neurotypical controls (NC) utilizing BrainStructuresAges, a machine learning MRI analysis pipeline. NC showed whole brain aging at a rate of 0.83 per chronological year compared with 1.57 in juvenile GM1 patients and 12.25 in late-infantile GM1 patients, accurately reflecting the clinical trajectories of the two disease subtypes. Accelerated and distinct brain aging was also observed throughout midbrain structures including the thalamus and caudate nucleus, hindbrain structures including the cerebellum and brainstem, and the ventricles in juvenile and late-infantile GM1 patients compared to NC. Predicted brain age and BSAGE both correlated with cross-sectional and longitudinal clinical assessments, indicating their importance as a surrogate neuroimaging outcome measures for clinical trials in GM1 gangliosidosis.

Published in Communications Medicine · training set

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