Longitudinal Study of Cognitive and Emotional Alterations in Amyotrophic Lateral Sclerosis: Clinical and Imaging Data

Abstract

Objectives: Extra-motor manifestations occur in 50% of patients with amyotrophic lateral sclerosis (ALS). These mainly concern cognition, emotional processing and behavior. Depression and anxiety are less frequent. Little is known about how these manifestations change as the disease progresses. Similarly, although cortical thinning has been well-documented at disease onset, there are scant data about cortical thinning over time and how this correlates with extra-motor manifestations. The present study therefore assessed cognitive, emotional and psychological state and cortical thinning in a group of patients with ALS at baseline and after a follow-up period.Methods: We assessed executive functions, facial emotion recognition, depressive and anxious symptoms, and cortical thinning in 43 patients with ALS at baseline, comparing them with 28 healthy controls, and 21 of them 9 months later. We looked for links among the extra-motor manifestations and correlations with cortical thickness.Results: At baseline, patients had poor executive function and recognition of complex emotions from the eyes, and more anxious and depressive symptoms than controls. At follow-up, only inhibition abilities had worsened. Cortical thinning was observed in bilateral pre-central regions and other parts of the cerebral cortex at baseline. Over time, it worsened in motor and extra-motor areas. Executive functions correlated with thinning in the middle and inferior frontal gyrus and orbitofrontal cortex.Conclusions: During follow-up, there was little deterioration in extra-motor manifestations and psychological state, despite continuing cortical thinning. Patients with affective Theory of Mind (ToM) changes seemed less depressed than the others. Impaired mental flexibility was subtended by prefrontal regions with cortical thinning.

Cognitive reserve protects ALS‐typical cognitive domains: A longitudinal study.

“…Details can be found in Table 1. In longitudinal imaging studies of ALS, high attrition rates of up to 94% are common due to the disease's rapid progression 12,22,23 . We had recruited 125 persons but only 38 participated at follow‐up.…”

“…In longitudinal imaging studies of ALS, high attrition rates of up to 94% are common due to the disease's rapid progression. 12,22,23 We had recruited 125 persons but only 38 participated at follow-up. Figure 1 outlines the flow of participants throughout the study.…”

Alteration of interoceptive sensitivity: expanding the spectrum of behavioural disorders in amyotrophic lateral sclerosis

“…Structural and functional neuroimaging studies showed significant cortical thinning and reduced functional activation in the pre-central gyrus and supplementary motor area [ 13 – 15 ] as well as in extra-motor regions such as the prefrontal and temporal cortices [ 15 , 16 ]. Interestingly, the involvement of limbic areas, including the insula, has been recently described in the neurodegenerative process of the ALS [ 10 , 17 , 18 ].…”

Longitudinal grey matter and metabolic contributions to cognitive changes in amyotrophic lateral sclerosis

“… 1 Even though ALS is commonly known as a motor disorder, a growing number of studies have demonstrated the involvement of extramotor regions underlying cognition and behaviour. 2 There is now a general recognition that ALS pathology is not restricted to a motor deficit, with about half of patients demonstrating evidence of cognitive impairments. 3 While such cognitive decline mainly concerns executive functions, 4 impairments of theory of mind (ToM) abilities have also been identified, 5 which refers to the ability of understanding mental states in others.…”

“…Structural imaging mainly highlighted the atrophy of cortical 7 and subcortical structures. 2 Such atrophy has been associated with cognitive changes, especially in frontal regions. 8 Among functional imaging methods, position emission tomography (PET) combined with 18F-fluorodeoxyglucose (FDG) demonstrated hypometabolism of the prefrontal cortex, fusiform gyrus and thalamus.…”