Amyotrophic lateral sclerosis (ALS) can be associated with a spectrum of cognitive and behavioural symptoms, but the related patterns of focal cortical atrophy in non-demented ALS patients remain largely unknown. We enrolled 48 non-demented ALS patients and 26 healthy controls for a comprehensive neuropsychological assessment and a magnetic resonance exam. Behavioural and cognitive impairment was defined on the basis of a data-driven multi-domain approach in 21 ALS patients. Averaged cortical thickness of 74 bilateral brain regions was used as a measure of cortical atrophy. Cortical thinning in a fronto-parietal network, suggesting a disease-specific pattern of neurodegeneration, was present in all patients, independent of cognitive and behavioural status. Between-group and correlational analyses revealed that inferior frontal, temporal, cingular and insular thinning are markers for cognitive and behavioural deficits, with language impairment mainly related to left temporal pole and insular involvement. These specific correlates support the concept of a spectrum of deficits, with an overlap between the ALS cognitive phenotypes and the syndromes of frontotemporal dementia.
Keywords: ALS, amyotrophic lateral sclerosis; ALSbi, ALS with mild behavioural impairment; ALSci, ALS with mild cognitive impairment; ALScn, cognitively-normal ALS; ALSimp, ALS with cognitive and/or behavioural impairment; Amyotrophic lateral sclerosis; C9+ ALS, ALS harbouring C9orf72 repeat expansion; C9– ALS, ALS without C9orf repeat expansion; CT, cortical thickness; Cognitive impairment; Cognitive profiles; Cortical thickness; FTD, frontotemporal dementia; GM, grey matter; HC, healthy control; MD, multi-domain; Temporal lobe.