RESUMO
Amyotrophic lateral sclerosis is characterized by rapidly evolving cognitive and brain impairments. While previous work revealed structural and functional alterations associated with cognitive decline in patients suffering from amyotrophic lateral sclerosis, the relationships between anatomo-functional changes and both disease's progression and the evolution of cognitive performance remain largely unexplored. Here, we took advantage of repeated multi-modal acquisitions in patients with amyotrophic lateral sclerosis over 1 year to assess the longitudinal sequence of grey matter atrophy, glucose metabolism and cognitive changes. Results revealed metabolic and structural changes over frontal, thalamic and temporal regions. Both cortical hypermetabolism and hypometabolism (right temporal gyrus and right angular gyrus, respectively) were associated with cognitive performance and thalamic hypometabolism during the follow-up testing session. Furthermore, the inferior frontal gyrus atrophy mediated the relation between early hypometabolism in this region and the subsequent decline of the theory of mind abilities. Marked volume loss was associated with larger hypometabolism and impaired cognitive performance. To our knowledge, this is the first study to longitudinally examine both grey matter volume and metabolic alteration patterns in patients with amyotrophic lateral sclerosis, over a mean follow-up time of 1 year. We identify how changes of the inferior frontal gyrus critically underly later cognitive performance, shedding new light on its high prognostic significance for amyotrophic lateral sclerosis-related changes. These results have important implications for our understanding of structural and functional changes associated with amyotrophic lateral sclerosis and how they underly cognitive impairments.
RESUMO
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.
RESUMO
It is now well recognized that, in addition to motor impairment, amyotrophic lateral sclerosis (ALS) may cause extra-motor clinical signs and symptoms. These can include the alteration of certain cognitive functions, impaired social cognition, and changes in the perception and processing of emotions. Where these extra-motor manifestations occur in ALS, they usually do so from disease onset. In about 10% of cases, the cognitive and behavioral changes meet the diagnostic criteria for frontotemporal dementia. The timecourse of behavioral and cognitive involvement in ALS is unclear. Whereas longitudinal studies have failed to show cognitive decline over time, some cross-sectional studies have demonstrated poorer cognitive performances in the advanced stages of the disease. Neuroimaging studies show that in ALS, extra-motor signs and symptoms are associated with specific brain lesions, but little is known about how they change over time. Finally, patients with ALS appear less depressed than might be expected, given the prognosis. Moreover, many patients achieve satisfactory psychosocial adjustment throughout the course of the disease, regardless of their degree of motor disability. There are scant longitudinal data on extra-motor impairment in ALS, and to our knowledge, no systematic review on this subject has yet been published. Even so, a better understanding of patients' clinical trajectory is essential if they are to be provided with tailored care and given the best possible support. We therefore undertook to review the evidence for extra-motor changes and their time course in ALS, in both the cognitive, emotional and psychological domains, with a view to identifying mechanisms that may help these patients cope with their disease.
RESUMO
Introduction: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive and extensive motor deficits. Patients may also have cognitive impairments or alteration of emotional processing. Very few studies, however, have looked at deficits in how they experience their own feelings (alexithymia). Methods: We assessed alexithymia in 28 patients with ALS using the 20-item Toronto Alexithymia Scale (TAS-20), comparing them with a control group matched for sex, age, and education level. We took into account both the total score of the TAS-20 and its three subscores corresponding to the three dimensions of alexithymia: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Patients also underwent a neuropsychological assessment and anatomical magnetic resonance imaging (MRI) in order to correlate cognitive performances and gray matter volume and level of alexithymia. Results: On average, ALS subjects had a significantly higher total score and DIF sub-score of the TAS-20 than controls indicating an increased alexithymia in patients. Total and DIF Scores correlated significantly and negatively to gray matter volume of the prefrontal cortex, right superior temporal pole and parahippocampal gyri. No correlations were found between scores on executive functions and those on the TAS-20. Conclusion: The first stage of one's own emotional processing seems to be affected in ALS independently of executive dysfunction. This trouble seems to be underpinned by cerebral regions that are well known to be both implicated in alexithymia in healthy subjects and altered in ALS.