Judith Newton

Screening for cognition and behaviour changes in ALS.

Abstract This study presents the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), developed for ALS patients with physical disability for use by health care professionals. The screen is designed to detect the specific profile of cognition and behaviour changes in ALS and to differentiate it from other disorders. Forty-eight ALS patients (none with evident dementia), 40 healthy controls and 20 carers were recruited. The ECAS, a 15–20-min screen, includes an ALS-Specific score (executive functions and social cognition; fluency; language); an ALS Non-specific score (memory; visuospatial functions); and a carer behaviour screen of five domains characteristic of frontotemporal dementia (FTD). Data from healthy controls produced abnormality cut-offs of 77/100 ALS-Specific score; 24/36 ALS Non-specific score; 105/136 ECAS Total. Twenty-nine percent of patients showed abnormal ALS-Specific scores, and 6% also showed abnormal ALS Non-specific scores. The most prevalent deficit occurred in language functions (35%) followed by executive functions and fluency (23% each). Forty percent of carers reported behaviour change in at least one domain, while 15% met criteria for possible FTD. In conclusion, the ECAS is an effective within-clinic assessment for ALS that determines the presence, severity and type of cognitive and/or behavioural changes, an essential first step to managing these symptoms.

Validation of the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS): A cognitive tool for motor disorders

Abstract Our objective was to assess the validity of the Edinburgh Cognitive and Behaviour ALS Screen (ECAS), a multi-domain screen designed to detect cognitive deficits in patients with motor disorders. Forty ALS patients (without pre-diagnosed dementia) and 40, age-, gender- and education-matched healthy controls were recruited. All participants underwent extensive neuropsychological assessment and the ECAS. Performance at neuropsychological assessment across five domains (fluency, executive function, language, memory and visuospatial function) was compared to the ECAS ALS-Specific (fluency, executive functions and social cognition, language), ALS Non-specific (memory, visuospatial functions), and Total scores. Data from the healthy controls produced population-based abnormality cut-offs: composite score performance ≤ 2 SD in any domain classified impairment at neuropsychological assessment. Thirty-three percent of patients were impaired, most commonly in a single domain (executive or language dysfunction). Receiver Operator Curve (ROC) analyses using ECAS Total scores and ALS-Specific scores revealed 85% sensitivity and 85% specificity in the detection of cognitive impairment characteristic of ALS (fluency, executive function, language). A five-point borderline range produced optimal values (ALS-Specific Score 77–82, and ECAS-Total Score 105–110). In conclusion, validation against gold standard extensive neuropsychology demonstrated that the ECAS is a screening tool with high sensitivity and specificity to impairment characteristic of ALS.

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

Abstract 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.

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 Kings 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 Kings 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 Kings 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.

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

Abstract 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.

11 Premorbid neuropsychiatric disease in patients with motor neurone disease in scotland

Objective Motor neurone disease (MND) is a rapidly progressive neurodegenerative disease, typically affecting limb, bulbar and respiratory muscles. Cognitive and behavioural change are also key features of the disease in up to 50% of patients (1). Neuropsychiatric symptoms may precede motor symptoms. A recent study highlighted that depression may be an independent risk factor for MND (2). We aimed to review the frequency of i) premorbid neuropsychiatric disease ii) premorbid psychotropic medication use iii) neuropsychiatric presentation of MND and iv) neuropsychiatric evolution of MND in an incident Scottish cohort. Method Patients were recruited via the Scottish MND Register (SMNDR). Patient characteristics (past medical and drug history, symptom onset and progression) were collected via the Scottish Clinical Audit Research and Evaluation for MND (CARE-MND) national care proforma. Results Incident cases of MND diagnosed in 2015/16 from a population-based national cohort will be presented. At interim analysis, 267 patients were eligible for review. 38 (14%) of patients had a documented past history of neuropsychiatric disease; 29 (11%) of mood disorder. 66 (25%) of patients had a history of psychotropic medication use. Frequency of premorbid neuropsychiatric disease will be compared with recent UK survey results (3). In 11 (4%) of patients, emotional lability, memory change or behavioural change was the presenting symptom. 32 (12%) of patients developed these features later in disease course. Conclusion From our preliminary analysis, rates of premorbid neuropsychiatric disease in patients with MND are comparable with population estimates. However, symptoms of low mood have been shown to have a negative impact on quality of life and are associated with faster disease progression (4). Clinical teams need to be mindful of these symptoms in all aspects of patient care, and ensure that appropriate therapies are offered and monitored.

Screening for cognitive and behavioural changes in ALS

Our objective was to explore the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients with a Japan ALS severity classification of Grade 3. In a 24-week, double-blind, randomized study, 25 patients who met all of the following criteria were enrolled: Japan ALS severity classification Grade 3; definite, probable, or probable-laboratory supported ALS (El Escorial/revised Airlie House); forced vital capacity (%FVC) 60%; duration of disease 3 years at consent; and change in the revised ALS functional rating scale (ALSFRS-R) score of –1 to –4 points during the 12-week pre-observation period. Patients received edaravone (n1⁄4 13) or placebo (n1⁄4 12) for six cycles. The efficacy outcome was change in the ALSFRS-R score. The least-squares mean change in the ALSFRS-R score standard error during the 24week treatment was –6.52 1.78 in the edaravone group and –6.00 1.83 in the placebo group; the difference of –0.52 2.46 was not statistically significant (p1⁄4 0.835). Incidence of adverse events was 92.3% (12/13) in the edaravone group and 100.0% (12/12) in the placebo group. There was no intergroup difference in the changes in the ALSFRS-R score. The incidences of adverse events were similar in the two groups.

Social and Emotional Cognition and Behaviour: Evidence of Subclinical frontotemporal Dementia in ALS

Background: The prevalence of frontotemporal dementia (FTD) in the ALS population is estimated to be between 30 to 50 percent. FTD is recognized to present as three distinct subtypes, including isolated behavioural change, a frontal cortical associated aphasia of a progressive non-fluent type and a temporal cortical associated aphasia of a fluent type characterized by loss of semantic knowledge. Given the aggressive course of the disease process, we wanted to identify ALS patients whose emerging FTD was rendering them less capable of independent decision-making. We developed an evaluation approach that included a behavioural inventory as well as screening measures of language change characteristic of either frontal dysfunction (FD) or temporal dysfunction (TD).