Cognition In Amyotrophic Lateral Sclerosis Research Articles

Screening for cognition in amyotrophic lateral sclerosis: test characteristics of a new screen

Cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) negatively influences the quality of life and survival, and, therefore, screening for these impairments is recommended. We developed a cognitive screening tool, the amyotrophic lateral sclerosis–frontotemporal dementia–cognitive screen (ALS–FTD–Cog) and aimed to validate it in patients with ALS. During the current study, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was published and we, therefore, decided to compare these two cognitive screening methods. The ALS–FTD–Cog was administered to 72 patients with ALS, 21 patients with behavioural variant FTD (bvFTD) and 34 healthy controls. Twenty-nine patients with ALS underwent the ECAS. ROC curve analyses were performed and sensitivity and specificity of the ALS–FTD–Cog and ECAS were calculated, with a neuropsychological examination (NPE) as the gold standard. Cognitive impairment was present in 28% of patients with ALS. ROC curve analyses of the ALS–FTD–Cog and ECAS showed an area under the curve (AUC) of 0.72 (95% CI 0.58–0.86) and 0.95 (95% CI 0.86–1.03), respectively. Compared to a full NPE, sensitivity and specificity of the ALS–FTD–Cog were 65.0% and 63.5% and of the ECAS 83.3% and 91.3%, respectively. The sensitivity and specificity of the ALS–FTD–Cog in patients with bvFTD were 94.4% and 100%, respectively. Test characteristics of the ALS–FTD–Cog were moderate, suggesting restricted practical value, as compared to a comprehensive NPE. The ECAS had an excellent AUC and high sensitivity and specificity, indicating that it is a valid screening instrument for cognitive impairment in ALS.

Progression of Brain Functional Connectivity Changes Associated with Altered Cognition in Amyotrophic Lateral Sclerosis (1531)

Progression of Brain Functional Connectivity Changes Associated with Altered Cognition in Amyotrophic Lateral Sclerosis (1531)

11. Neurophysiological correlates of impaired cognition in Amyotrophic Lateral Sclerosis

11. Neurophysiological correlates of impaired cognition in Amyotrophic Lateral Sclerosis

Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study (P6.326)

Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study (P6.326)

Meta-analysis of social cognition in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is associated with executive dysfunction and behavioural impairment. Recent studies suggested that social cognitive deficits might also be a prominent feature of ALS. Current meta-analysis aimed to summarize available evidence for deficits in social cognition including theory of mind (ToM) and emotion recognition in ALS. In this meta-analysis of 15 studies, facial emotion recognition and ToM performances of 389 patients with ALS and 471 healthy controls were compared. ALS was associated with significant impairments with medium effect sizes in ToM (d = .65) and facial emotion recognition (d = .69). Among individual emotions recognition of disgust and surprise were particularly impaired. Deficits in perspective taking (d = .73) aspects of ToM (ToM-PT) was more pronounced in comparison to decoding (d = .28) aspects of ToM (ToM-decoding). The severity of social cognitive impairment was similar to level of executive dysfunction and there was a significant relationship between social cognition and executive dysfunction. Deficits in social cognition are part of the cognitive phenotype of ALS.

Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study.

Background: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. Executive dysfunction is common in patients with ALS, with up to 50% of patients performing within an impaired range. There is evidence that social cognitive deficits associated with ALS are a function of deficits in executive function. The ‘Reading the Mind in the Eyes’ Test is a recognized test of social cognitive function, although the reliability of this instrument remains to be established. Methodology: Patients with ALS (n = 106), and age and IQ matched controls (n = 50) were recruited and asked to perform the Reading the Mind in the Eyes Test as part of an on-going population-based study of cognitive function. ALS patients were sub-stratified based on the presence, and/or extent of executive dysfunction. Results: Cronbach’s Alpha of .73 was observed, indicating good reliability on this measure. Split-half reliability analysis further confirms these findings (p = 0.826). The Reading the Mind in the Eyes test had excellent psychometric properties when discriminating between ALS patients who are cognitively intact, and those who have executive impairment, with an overall medium difficulty. There was a large magnitude significant difference between patients and controls (p< 0.001; η2 = .19). Post-hoc analysis revealed that controls performed significantly higher than patients with executive impairment (p< 0.001), and patients with single executive deficits (p = 0.002). Conclusion: Executive dysfunction impacts on social cognitive performance. This study contributes not only to the psychometric knowledge of this measure, but also to the usability, efficacy, and reliability of social cognitive assessment in ALS. Using population-specific normative data, we confirm the Reading the Mind in the Eyes Test is a reliable measure of social cognitive processes in ALS.

TDP-43 pathology and cognition in ALS: A prospective clinicopathologic correlation study.

Although a systematic spread of pathologic TDP-43 expression throughout the CNS in amyotrophic lateral sclerosis (ALS) has been proposed, the relationship between cognition and the extent and neuroanatomic distribution of TDP-43 pathology has not received considerable attention. We investigated the association between cognitive functioning and the extent of TDP-43 pathology in postmortem CNS tissue from 18 patients with ALS stratified into 3 groups based on detailed prospective neuropsychological testing (cognitively not impaired, n = 6; cognitively impaired, n = 6; ALS- frontotemporal dementia [FTD], n = 6) and analyzed these cases for clinicopathologic correlations. Our findings demonstrate a close relationship between cognition and the extent of TDP-43 pathology in non-primary motor areas with a striking difference between ALS-FTD and the 2 other cognitive groups. The specificity of our results was underscored by 2 key findings: first, the absence of an Alzheimer pathology effect, a common confounder in older patients; second, the lack of correlations between the primary motor regions with the highest TDP-43 intensity and cognitive status. Our data suggest a distinct dynamic of TDP-43 progression and distribution in ALS-FTD in contrast to ALS without FTD.

Cognition and Social Cognition in Amyotrophic Lateral Sclerosis in an Argentinean-Cohort. Preliminary data (P6.244)

Cognition and Social Cognition in Amyotrophic Lateral Sclerosis in an Argentinean-Cohort. Preliminary data (P6.244)

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

Background/Aims: A substantial proportion of amyotrophic lateral sclerosis (ALS) patients develop cognitive impairments. Longitudinal investigations of cognition in ALS have shown mixed results. While some authors report that cognitive performance remains stable as the disease progresses, others have found evidence for deterioration in various domains. Our objective was to investigate cognitive performance in ALS longitudinally, using the example of executive functions. Methods: 93 ALS patients and 73 age-, sex- and education-matched healthy controls underwent up to four neuropsychological evaluations, separated by 3- to 6-month intervals. We examined whether performance declined longitudinally on seven tests assessing various sub-components of executive functioning. Furthermore, we assigned an executive-performance-based ‘cognitive status' to each participant for every evaluation, examining whether cognitive deterioration (if present) was modulated by their baseline cognitive status and whether cognitive status changed over time. Results: Regardless of their cognitive status at baseline, ALS patients showed no significant decline in the sub-components of executive functioning. Conclusion: Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS.

Impaired cognitive flexibility in amyotrophic lateral sclerosis.

Up to half of patients with amyotrophic lateral sclerosis (ALS) may have cognitive difficulty, but most cognitive measures are confounded by a motor component. Studies relating impaired cognition in ALS to disease in gray matter and white matter are rare. Our objective was to assess executive function in patients with ALS using a simple, untimed measure with minimal motor demands, and to relate performance to structural disease. We gave the Visual-Verbal Test to 56 patients with ALS and 29 matched healthy controls. This brief, untimed measure of cognitive flexibility first assesses participants' ability to identify a feature shared by 3 of 4 simple geometric designs. The participants' cognitive flexibility is challenged when they are next asked to identify a different feature shared by another combination of 3 of the same 4 geometric designs. In a subset of 17 patients who underwent magnetic resonance imaging, regression analyses related test performance to gray matter atrophy and reduced white matter fractional anisotropy. The patients with ALS showed significant impairment in cognitive flexibility (P<0.01), with 48.2% making an error on the test. Regression analyses related impaired cognitive flexibility to gray matter atrophy in inferior frontal and insular regions, and to reduced fractional anisotropy in white matter projections in the inferior fronto-occipital and uncinate fasciculi and corpus callosum. Our patients with ALS had impaired cognitive flexibility on an untimed measure with minimal motor demands, a finding related in part to a large-scale frontal network that is degraded in ALS.

Cortical thinning and its relation to cognition in amyotrophic lateral sclerosis

Clinical, genetic, and pathological findings suggest a close relationship between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We studied the patterns of cortical atrophy across the spectrum between ALS and ALS-FTD. A surface-based morphometry analysis based on an age- and sex-matched sample of 81 ALS patients and 62 healthy control subjects (HC) was conducted. In addition, we used an age-matched subsample of 57 ALS patients and 31 HC to compare cortical thickness between 3 groups of neuropsychologically characterized ALS patients: (1) cognitively unimpaired; (2) cognitively impaired; and (3) ALS-FTD patients. Compared with HC, the entire sample of patients demonstrated cortical thinning in the bilateral precentral gyrus, right precuneus, and right frontal and temporal lobes. ALS-FTD patients showed cortical thinning in regions including the frontal and temporal gyri and the posterior cingulate cortex. Cognitively impaired ALS patients showed cortical thinning in regions largely overlapping with those found in ALS-FTD, but changes were less widespread. In conclusion, the cognitive status of ALS subjects is associated with different patterns of cortical atrophy.

The Relationship between Depressive Symptoms, Disease State, and Cognition in Amyotrophic Lateral Sclerosis.

Cognitive impairment (CI) in amyotrophic lateral sclerosis (ALS) may present a serious barrier to a patient’s wellbeing and significantly decrease quality of life. Although reports of CI in ALS without frank dementia are becoming quite common, questions remain regarding the specific cognitive domains affected, as well as how other psychological and medical factors may impact cognitive functioning in these patients. Additionally, the influence of depressive symptoms on disease processes is not known. We aimed to address these questions by completing extensive neuropsychological tests with 22 patients with ALS and 17 healthy volunteers. A subgroup of these patients also completed questionnaires to measure depressive and vegetative symptoms. We tested for overall cognitive differences between groups, the influence of physical (e.g., bulbar and limb), vegetative (e.g., fatigue), and depressive symptoms on cognitive performance, and the relationship between depressive symptoms and disease severity in ALS. Overall, patients performed more poorly than healthy controls (HCs), most notably on tests of executive functioning and learning and memory. Results suggest that true cognitive performance differences exist between patients with ALS and HCs, as these differences were not changed by the presence of vegetative or depressive symptoms. There was no effect of limb or bulbar symptoms on cognitive functioning. Also, patients were not any more depressed than HCs, however increased depressive scores correlated with faster disease progression and decreased limb function. Collectively, it is suggested that translational advances in psychological intervention for those with CI and depression become emphasized in future research.

Social Cognition in Amyotrophic Lateral Sclerosis

SUMMARY There is an overlap between amyotrophic lateral sclerosis and frontotemporal dementia. Approximately 15% of amyotrophic lateral sclerosis patients suffer from frontotemporal dementia characterized by behavioral change while a further third experience subtle executive dysfunction (typically letter fluency deficits) and corresponding prefrontal changes. Behavior change appears prevalent with apathy being the most prominent feature. Reports of social and emotional cognition deficits are increasing. Deficits have been described on theory of mind tasks including interpretation of stories and cartoons, faux pas detection and in the judgment of preference based on direction of eye-gaze. Impairments in emotional face and prosody perception and emotional enhancement of memory have been reported, and decision making (with and without risk) appears affected. The role of executive dysfunction in this social cognition deficit remains unresolved and more direct evidence of oribitofrontal involvement has yet to be found. Implications for healthcare provision are discussed with deterioration of social interaction with carers predicted.

Deficits in emotional and social cognition in amyotrophic lateral sclerosis.

These studies investigated whether non-demented ALS patients display impairments on tests of emotional decision making and social and emotional cognition, sensitive to frontal variant Frontotemporal Dementia (fvFTD). Previous studies have shown predominant executive dysfunction and dorsolateral prefrontal involvement in ALS, but evidence of other prefrontal dysfunction implicated in fvFTD is sparse. In Study A, 19 ALS patients and 20 healthy controls undertook a test of affective decision making, modified Iowa Gambling Task (IGT). Behavioral measures included the Frontal Systems Behavior Scale. In Study B, 14 ALS patients and 20 controls undertook tests of social and emotional cognition (Judgment of Preference based on eye gaze, the Mind in the Eyes, recognition of Facial Expressions of Emotion). In Study A, ALS patients demonstrated a significantly different performance profile from healthy controls on the IGT and did not learn to avoid the disadvantageous stimuli (Block 3, d = 0.60, Block 4 days = 0.68). Behavior ratings showed increased apathy from premorbid levels. In Study B, ALS patients were impaired on attentionally demanding (d = 3.12) and undemanding (d = 7.52) conditions of the Judgment of Preference task, despite many showing intact executive functions. A smaller subset showed impaired emotion recognition. Behavior change was also evident. The findings reveal a Theory of Mind deficit on a simple test that was dissociated from the presence of executive dysfunction and suggests a profile of cognitive and behavioral dysfunction indicative of a subclinical fvFTD syndrome. The relative contribution of prefrontal pathways to the cognitive profile in ALS is considered.

Association between dysarthria and cognitive impairment in ALS: A prospective study

Several studies have demonstrated impaired cognition in amyotrophic lateral sclerosis (ALS) patients, but it has been difficult to identify risk factors for this impairment. An association between cognitive changes and bulbar site of onset or dysarthria has been suggested, but the findings are variable. We tested for both associations in a large cohort of ALS patients. At the time of diagnosis of sporadic ALS, all patients (n=355) in this prospective study underwent comprehensive neuropsychological testing. In addition, a subset of 175 patients underwent a detailed assessment of dysarthria, which was quantified using the Appel ALS Score (AALSS). ALS patients with bulbar site of onset performed significantly worse than limb onset patients on a few timed ((VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05)) tests of frontal lobe functions, but the significance could not be replicated when motor impairment was accommodated into the tests ((VSAT-errors, p=0.73), (Stroop interference, p=0.08)). ALS patients with dysarthria performed significantly worse than non-dysarthrics on multiple timed ((BD, p<0.05), (VSAT-time, p<0.05), (Stroop Color, p<0.05), (Stroop Word, p<0.05), (Trails A, p<0.05), (Trails B, p<0.05)) neuropsychological tests, and the significance was maintained when motor impairment was accommodated into one of these tests (Stroop interference, p<0.05). Additionally, dysarthrics performed significantly worse on two untimed measures of cognition ((Similarities, p<0.05), (Rey Copy, p<0.05)). Cognitive functioning in ALS does not associate with the site of onset and has a moderate association with dysarthria.

Psychosocial factors and cognition in amyotrophic lateral sclerosis.

(2003). Psychosocial factors and cognition in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders: Vol. 4, No. 4, pp. 217-224.