Longitudinal Characterization of the FTD-ALS Spectrum

Abstract

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are heterogeneous neurodegenerative diseases that, despite presenting divergent clinical features, can occur within the same person. Based on shared genetics and pathology, characterizing FTD-ALS with clinical and quantitative imaging measures over time may highlight patterns of disease progression and specific brain system vulnerabilities, leading to needed biomarkers development. We propose to build, characterize and compare concurrent FTD-ALS, ALS and FTD cohorts with a prospective observational cohort study performed at Massachusetts General Hospital, including clinical and MRI based imaging measures specific to both ALS and FTD. We will perform quantitative cortical thickness and sub-cortical structures analysis, white matter anatomical and functional integrity evaluations, correlations between anatomical and clinical measures, both within patient and inter-patient populations. To date, there are no longitudinal studies or quantitative cortical thickness evaluations across the entire FTD-ALS continuum. Our longitudinal comprehensive and specialized assessments will lead to the development of a unique dataset evaluating the full FTD-ALS spectrum with standardized measures in a multidisciplinary approach. This will provide the basis for further FTD-ALS research and it will contribute to the development of quantitative biomarkers of disease and disease progression across clinically heterogeneous diseases, impacting both clinical and research practices.