P23. Basal ganglia pathology in amyotrophic lateral sclerosis is associated with cognitive and behavioural changes

Abstract

Introduction Extrapyramidal, cognitive, and sensory deficits are increasingly recognised in patients with amyotrophic lateral sclerosis (ALS), suggesting dysfunction of specific frontostriatal, nigrostriatal and corticobasal circuits. While significant basal ganglia involvement has been demonstrated by recent histopathology and neuroimaging studies, subcortical pathology in ALS has not been studied in relation to cognitive and behavioural deficits. Here, we evaluate basal ganglia involvement along the continuum of ALS, ALS with cognitive and behavioural deficits, and ALS with comorbid frontotemporal dementia (ALS-FTD), using multiple, complementary imaging techniques. Methods Volumetric, shape, and density analyses were performed for seven subcortical structures: thalamus, amygdala, nucleus accumbens, hippocampus, caudate nucleus, pallidum, and putamen. Patients were allocated into three study-groups: C9orf72-negative ALS patients without cognitive or behavioural impairment (“ALS-Nci”, n = 42), ALS patients with cognitive and/or behavioural impairment (“ALS-Plus”, n = 18), and ALS patients with comorbid FTD (“ALS-FTD”, n = 7), matched for disease duration and severity. An age-, gender-, and education matched group of healthy controls was also included (“HC”, n = 39). Results Volumetric analyses revealed intergroup differences for six subcortical structures when adjusting for total intracranial volume and controlling for age: caudate nucleus (p = 0.023), thalamus (p Conclusion A gradient of incremental basal ganglia pathology was observed across the ALS/ALS-FTD spectrum, suggesting that the degree of subcortical grey matter pathology in C9orf72-negative ALS is closely associated with cognitive and behavioural changes. The observed changes in shape and lesion location are indicating a disease specific degeneration of subcortical structures and suggest the disruption of frontrostriatal and corticobasal circuits in ALS.