ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS.

OBJECTIVE: To elucidate the relationship between disease stage in amyotrophic lateral sclerosis (ALS), as measured with the King's Clinical Staging System, and cognitive and behavioral change, measured with the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). METHODS: A large multicenter observational cohort of 161 cross-sectional patients with ALS and 80 healthy matched controls were recruited across 3 research sites (Dublin, Edinburgh, and London). Participants were administered the ECAS and categorized into independent groups based on their King's clinical disease stage at time of testing. RESULTS: Significant differences were observed between patients and controls on all subtests of the ECAS except for visuospatial functioning. A significant cross-sectional effect was observed across disease stages for ALS-specific functions (executive, language, letter fluency) and ECAS total score but not for ALS-nonspecific functions (memory, visuospatial). Rates of ALS-specific impairment and behavioral change were also related to disease stage. The relationship between cognitive function and disease stage may be due to letter fluency impairment, whereas higher rates of all behavioral domains were seen in later King's stage. The presence of bulbar signs, but not site of onset, was significantly related to ALS-specific, ECAS total, and behavioral scores. CONCLUSION: ALS-specific cognitive deficits and behavioral impairment are more frequent with more severe disease stage. By end-stage disease, only a small percentage of patients are free of neuropsychological impairment. The presence of bulbar symptoms exaggerates the differences observed between disease stages. These findings suggest that cognitive and behavioral change should be incorporated into ALS diagnostic criteria and should be included in future staging systems.

Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function.

Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.

Memory complaints in epilepsy: An examination of the role of mood and illness perceptions.

The study examined the role of mood and illness perceptions in explaining the variance in the memory complaints of patients with epilepsy. METHOD: Forty-four patients from an outpatient tertiary care center and 43 volunteer controls completed a formal assessment of memory and a verbal fluency test, as well as validated self-report questionnaires on memory complaints, mood, and illness perceptions. RESULTS: In hierarchical multiple regression analyses, objective memory test performance and verbal fluency did not contribute significantly to the variance in memory complaints for either patients or controls. In patients, illness perceptions and mood were highly correlated. Illness perceptions correlated more highly with memory complaints than mood and were therefore added to the multiple regression analysis. This accounted for an additional 25% of the variance, after controlling for objective memory test performance and verbal fluency, and the model was significant (model B). In order to compare with other studies, mood was added to a second model, instead of illness perceptions. This accounted for an additional 24% of the variance, which was again significant (model C). In controls, low mood accounted for 11% of the variance in memory complaints (model C2). SUMMARY: A measure of illness perceptions was more highly correlated with the memory complaints of patients with epilepsy than with a measure of mood. In a hierarchical multiple regression model, illness perceptions accounted for 25% of the variance in memory complaints. Illness perceptions could provide useful information in a clinical investigation into the self-reported memory complaints of patients with epilepsy, alongside the assessment of mood and formal memory testing.

ECAS A-B-C: alternate forms of the Edinburgh Cognitive and Behavioural ALS Screen.

BACKGROUND: The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is a short assessment by which neuropsychological symptoms can be detected and quantified in people with ALS. To avoid potential practice effects with repeated administration, here we present alternative versions of the ECAS suitable for measuring change over time. OBJECTIVE: To develop two alternate versions of the ECAS: ECAS-B and ECAS-C. METHOD: One hundred and forty-nine healthy adult participants were recruited. Thirty participants completed a pilot study in developing the alternate versions. Two groups of 40 participants were administered the ECAS-B or ECAS-C and compared to published data of the original ECAS (ECAS-A) to determine equivalence. An additional 39 participants were administered the ECAS consecutively, either repeating the original version (ECAS-A-A-A) serially or the different versions (ECAS-A-B-C) to determine potential practice effects. Recordings of assessments were scored by a second researcher to determine inter-rater reliability. RESULTS: No significant differences were found between versions (A, B, C) of the composite performance measures of ALS Specific, ALS Non-Specific, and ECAS Total scores. Repeated serial administration of ECAS-A (A-A-A) produced some practice effects for composite scores, whereas no such effects were found when alternate versions were administered serially (A-B-C). Exceptionally high intra-class correlations were found for all three versions of the ECAS suggesting a high degree of rater agreement. CONCLUSION: The newly developed alternate forms of the ECAS are both highly equitable to the original ECAS-A and enable avoidance of practice effects, thus supporting their use in measuring cognition and behaviour over time.

Measuring reliable change in cognition using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

BACKGROUND: Cognitive impairment affects approximately 50% of people with amyotrophic lateral sclerosis (ALS). Research has indicated that impairment may worsen with disease progression. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was designed to measure neuropsychological functioning in ALS, with its alternate forms (ECAS-A, B, and C) allowing for serial assessment over time. OBJECTIVE: The aim of the present study was to establish reliable change scores for the alternate forms of the ECAS, and to explore practice effects and test-retest reliability of the ECAS's alternate forms. METHOD: Eighty healthy participants were recruited, with 57 completing two and 51 completing three assessments. Participants were administered alternate versions of the ECAS serially (A-B-C) at four-month intervals. Intra-class correlation analysis was employed to explore test-retest reliability, while analysis of variance was used to examine the presence of practice effects. Reliable change indices (RCI) and regression-based methods were utilized to establish change scores for the ECAS alternate forms. RESULTS: Test-retest reliability was excellent for ALS Specific, ALS Non-Specific, and ECAS Total scores of the combined ECAS A, B, and C (all > .90). No significant practice effects were observed over the three testing sessions. RCI and regression-based methods produced similar change scores. CONCLUSION: The alternate forms of the ECAS possess excellent test-retest reliability in a healthy control sample, with no significant practice effects. The use of conservative RCI scores is recommended. Therefore, a change of ≥8, ≥4, and ≥9 for ALS Specific, ALS Non-Specific, and ECAS Total score is required for reliable change.

Multidimensional apathy and executive dysfunction in amyotrophic lateral sclerosis.

Apathy and cognitive dysfunction are prominent symptoms of Amyotrophic lateral sclerosis (ALS). More specifically ALS patients show increased Initiation apathy-a lack of motivation for self-generation of thoughts as assessed by the Dimensional Apathy Scale. This study aimed to investigate the cognitive underpinnings of apathy subtypes in ALS. We hypothesized that increased Initiation apathy would be associated deficits on tests of intrinsic response generation, such as verbal fluency. We also explored the relationship of other apathy subtypes to cognitive processes, in particular emotional apathy with emotional and social cognition deficits and executive apathy with planning and goal management deficits. ALS patients, and their carers (N = 30), and healthy matched controls, and their informants (N = 29) were recruited. All participants completed self- and informant/carer-rated Dimensional Apathy Scale, to quantify apathy subtypes (Executive, Emotional and Initiation), along with standard apathy and depression measures. Patients and controls completed the Edinburgh Cognitive and behavioural ALS Screen, and a comprehensive neuropsychological battery including emotional recognition, social cognition, intrinsic response generation tasks (verbal fluency and random number generation) and a new ecologically valid, computerised measure of planning and goal management. The results demonstrated that increased Initiation apathy was the only significantly elevated subtype in ALS (self-rated p < .05, informant/carer-rated p < .01). Initiation apathy was found to be significantly associated with verbal fluency deficit, while Emotional apathy was significantly associated with emotional recognition deficits. No associations were found between apathy subtypes and depression or in controls. This is the first study to show specific associations between apathy subtypes (Emotional and Initiation) and executive and emotional cognitive dysfunction, indicating possible distinct underlying mechanisms to these demotivational symptoms.