Cognitive and Behavioral Features in ALS: Beyond Motor Impairment in ALS-FTD Spectrum Disorders

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Background

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are considered as part of a clinical and neuropathological continuum, involving the more recently evolved functions of the human brain such as fine motor skills, walking, language, executive function, emotional control, and social behavior. Motor and cognitive phenotypes can vary considerably from patient to patient and evolve by different pathways during disease progression. The pathophysiological mechanisms underlying this clinical heterogeneity are still poorly understood, contributing to the difficulty in determining potential genetic and environmental factors. Recent advances in neural biomarkers, neuropsychological assessments, neuroimaging, and neurophysiological techniques endeavor to unravel the complex issue of cognitive/behavioral and motor impairments by determining the cause and effect of this association.

Over the last decades, significant advances have been achieved in this field of knowledge, especially from research groups that are able to overcome the classical conception of ALS as a simple neuromuscular disorder and of FTD being a mere form of dementia, through the translational utility of neuroimaging, neuropsychology and neurophysiology in a translational way. Despite these recent advancements, several key questions remain. Cross-sectional studies suggest that cognitive decline coincides with disease progression. However, longitudinal studies tend to show little decline within patients over time. This is largely due to high rates of attrition, especially in those with more severe disease progression.

This Research Topic will contribute to the improved understanding of the complex pathophysiological mechanisms and also to further phenotype characterization, disease management and patient care. For this project we welcome submissions of Perspectives, Original Research, Systematic Reviews, Brief Research Reports, and Case Series regarding potential topics including, but not limited to, the following:

- Novel neuropsychological assessments to better characterize ALS, FTD, and ALS-FTD patients in all stages of disease;
- Novel neurophysiological techniques that are able to identify or predict motor involvement and/or cognitive impairment in ALS, FTD, and ALS-FTD patients;
- The employment of neuroimaging techniques that are able to identify and stratify patients with different motor and cognitive/behavioral symptoms;
- Case series that investigate the heterogeneity of cognitive and motor features in ALS-FTD patients;
- Analyses of the effects of cognitive/behavioral impairment on clinical management of ALS patients, their families, and caregivers;
- Studies comparing cognitive and behavioral impairments in ALS to other neurodegenerative diseases (e.g. Alzheimer’s disease; Parkinson’s disease);
- The identification of new genetic or humoral biomarkers of ALS and FTD;
- Longitudinal studies of cognition in ALS, addressing the major limitation of high attrition;
- In depth studies of memory in ALS, teasing apart if pure memory deficits exist independent of executive deficits.

Keywords: Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Neuroimaging, Neurophysiology, Neuropsychology

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