Lewis Connor J, Chipman Selby I, D'Souza Precilla, Johnston Jean M, Yousef Muhammad H, Gahl William A, Tifft Cynthia J, Acosta Maria T
Office of the Clinical Director, National Human Genome Research Institute, Bethesda MD 20892 USA.
Medical Genetics Branch, National Human Genome Research Institute, Bethesda MD 20892 USA.
medRxiv. 2025 Apr 25:2025.04.23.25326206. doi: 10.1101/2025.04.23.25326206.
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 , 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.
GM1神经节苷脂沉积症是一种遗传性、进行性且致命的神经退行性溶酶体贮积症，目前尚无获批的治疗方法。我们使用一种机器学习MRI分析流程，对41例II型GM1神经节苷脂沉积症患者的81次MRI扫描以及556名神经典型对照（NC）的897次MRI扫描计算了预测脑龄和脑结构年龄差距估计（BSAGE）。与青少年GM1患者的每年1.57以及晚期婴儿型GM1患者的每年12.25相比，NC的全脑衰老速度为每年0.83，准确反映了两种疾病亚型的临床病程。与NC相比，在青少年和晚期婴儿型GM1患者的整个中脑结构（包括丘脑和尾状核）、后脑结构（包括小脑和脑干）以及脑室中也观察到了加速且明显的脑衰老。预测脑龄和BSAGE均与横断面和纵向临床评估相关，表明它们作为GM1神经节苷脂沉积症临床试验的替代神经影像学结局指标的重要性。
