Multimodal MRI quantification of the common neurostructural bases within the FTD-ALS continuum

Abstract

The continuum hypothesis linking the behavioral variant of frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) is supported by clinical, pathological, genetic, and neuroimaging evidence. In the present multimodal magnetic resonance study, we characterized the site and extent of shared neurostructural changes in gray and white matter in 20 bvFTD and 19 ALS patients without dementia. We found an overlap of macrostructural and microstructural damage in both patient groups compared with healthy controls, involving the right orbital and the bilateral anterior cingulate cortices, the corticospinal tract and corpus callosum. The quantification of gray and white matter damage within the areas of shared alterations highlighted a higher degree of atrophy in orbitofrontal and frontomedial regions in patients with more severe executive and/or behavioral symptoms, and a higher degree of degeneration in the motor pathway in patients with more severe motor neuron disorders. Our finding provides additional evidence confirming the FTD-ALS continuum hypothesis and supports the notion of a bimodal but convergent pattern of neurostructural changes characterizing bvFTD and ALS.

Keywords: ALS-FTD continuum hypothesis; Amyotrophic lateral sclerosis; Behavioral variant of frontotemporal dementia; Corticospinal tract; Tract-based spatial statistics; Voxel-based morphometry.