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Cortical microstructure in the amyotrophic lateral sclerosis-frontotemporal dementia continuum
Ignacio Illán-Gala1, Victor Montal2, Jordi Pegueroles2
1From the Sant Pau Memory Unit (I.I.-G., V.M., J.P., E.V., D.A., O.D.-I., L.M.-R., M.B.S.-S., A.S., L.V., I.S., I.B., S.V., R.B., J.C., A.L., J.F.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona; Neuromuscular Diseases Unit (N.d.L., J.T.-S., E.C.-V., R.R.-G.), Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER) (N.d.L., J.T.-S., E.C.-V., R.R.-G.), Valencia; Barcelona Down Medical Center (I.I.G., L.V., J.F.), Fundació Catalana de Síndrome de Down, Barcelona; and Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (I.I.-G., V.M., J.P., E.V., D.A., O.D.-I., I.B., R.B., J.C., A.L., J.F.), CIBERNED, Madrid, Spain. iillan@santpau.cat jfortea@santpau.cat.
Cortical microstructure changes, specifically increased mean diffusivity, are linked to cognitive impairment in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These changes may indicate extramotor neurodegeneration in the ALS-FTD spectrum.
Area of Science:
- Neuroimaging
- Neurodegeneration
- Neurology
Background:
- Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a clinical continuum with overlapping pathological features.
- Understanding the neuroanatomical basis of cognitive and behavioral changes in this spectrum is crucial for diagnosis and treatment.
Purpose of the Study:
- To characterize cortical macrostructure and microstructure alterations associated with behavioral and cognitive changes in the ALS-FTD continuum.
- To identify potential imaging biomarkers for extramotor neurodegeneration.
Main Methods:
- Prospective recruitment of 88 participants: 31 with ALS, 20 with behavioral variant FTD (bvFTD), and 37 controls.
- 3T MRI (structural and diffusion-weighted imaging) to compute cortical thickness and mean diffusivity.
- Cognitive and behavioral assessment using the Edinburgh Cognitive and Behavioral ALS Screen to stratify ALS participants.
Main Results:
- ALS participants without cognitive/behavioral impairment (ALSno-cbi) showed reduced cortical thickness in the dorsal motor cortex.
- ALS participants with cognitive/behavioral impairment (ALScbi) exhibited thinning in frontoinsular and temporal regions.
- Progressive cortical mean diffusivity changes were observed across ALSno-cbi, ALScbi, and bvFTD groups, with increased diffusivity in the prefrontal cortex in ALScbi even without cortical thinning.
Conclusions:
- Cortical mean diffusivity serves as a potential biomarker for extramotor neurodegeneration within the ALS-FTD spectrum.
- Cortical microstructure alterations correlate with cognitive impairment in ALS and FTD.
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