Cortical markers of cognitive syndromes in amyotrophic lateral sclerosis

Abstract

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.

Fig. 1

Neuropsychological profiles of ALS patients according to the MD classification. ALScn = cognitively-normal ALS patients; ALSbi = ALS patients mild behavioural impairment; ALSciα = ALS patients with mild dysexecutive impairment (with ≥2 performances below cut-off on tests addressing executive cognitive functions); ALSciβ = ALS patients with ≥2 performances below cut-off on tests addressing non-executive cognitive functions (social cognition, language and memory); ALSciα + β = ALS patients with a mixed cognitive profile; ALSbi-ciβ = ALSbi patients with non-executive cognitive impairment; ALSbi-ciα + β = ALSbi patients with the ALSci α + β profile.

Fig. 2

Distribution of the cortical thinning in patients with ALS considering their cognitive status. Yellow indicates thinning in ALSimp patients compared to HC volunteers; blue indicates thinning in ALScn patients compared to HC volunteers; green indicates overlap between these comparisons. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Distribution of the cortical thinning (in red) on the pial surface of the right hemisphere (lateral and inferior views) in ALSimp patients compared to ALScn patients. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)