Cognitive impairment in ALS: screening tools, experiences and prognosis

Cognitive impairment in ALS: screening tools, experiences and prognosisA validated Norwegian version of the Edinburgh cognitive and behavioural ALS screen (ECAS) is available.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). Typically, cognitive impairment limit the ability to process complex information, interact and communicate, and adds to caregiver burden. As a first step to detect cognitive changes and manage ALS specific cognitive challenges, early and repeated screening is recommended. Research collaboration highlight a need for validated tests in other languages than English. Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment and driving ability is also needed. Few studies have explored interpersonal relations between people with ALS and their carers. To gain a validated test for screening of cognitive impairment in Norwegian patients with ALS and knowledge about how to interpret test scores, a multicenter project was carried out in four studies. The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) may have some advantages over other screening tests that have been used for assessing cognitive changes in ALS patients. However, recommendations for ALS-specific tests with sound psychometric properties are urgently needed. The Norwegian version of ECAS (ECAS-N) with age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance is provided. The ECAS-N holds promise for detecting cognitive impairment in Norwegian patients with ALS and can be used in international research. However, cut-off scores are situational and could vary between cultures. Researchers should be aware of differences between tests applied in studies. The ECAS-N showed a potential to be used by different testers in clinical practice and research to screen patients with ALS who speak Norwegian and for documenting cognitive impairment over time. Patients with ALS and cognitive decline have demonstrated shorter survival compared to the patients without cognitive decline. The practice and implementation of both bilevel positive airway pressure device (BiPAP) and percutaneous endoscopic gastrostomy (PEG) did not differ among the ALS patients with and without cognitive decline in Norway. In progress An article aimed to report the use of ECAS-N as a test to predict early changes in car driving is in progress. Here, patients with ALS were administered the ECAS-N 4 months after being diagnosed (baseline) and 8-month follow-up, along with driving status. A priory defined hypotheses were evaluated using t-test, regression analysis and visual inspection. A qualitative interview study designed to better understand how cognitive impairment due to ALS influences close relations in everyday life are conducted. Four patients and four carers were interviewed 8 months after diagnosis. Data were analyzed by use of a thematically analysis. Results are presented in Marit Oseland’s Master thesis titled; Det har blitt et rollespill, which was defended at Oslo Metropolitan University (OsloMet) at 10th of December 2021. As the results are planned to be published in a scientific journal, the results are provisionally withheld from the public. Preliminary results were presented at the 7th Norwegian congress in Occupational Therapy, Stavanger 19.-21. 2022.

Cognitive impairment in ALS: screening tools, experiences and prognosisThe Edinburgh Cognitive and Behavioural ALS Screen is translated and culturally adapted into Norwegian (ECAS-N). Country specific cut-off values for abnormal performance is provided. Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is needed.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). To gain a validated test for screening of cognitive impairment in Norwegian patients with ALS and knowledge about how to interpret test scores, a multicentre project was carried out in four studies. Study 1 is a systematic review aimed to assess the properties of all measurements used in ALS and cognitive screening. Study 2 is twofold. In part one, the Edinburgh Cognitive and Behavioural ALS Screen was translated and culturally adapted into Norwegian (ECAS-N). In part 2 (2015/11598 and 2016/3166 - Data Privacy Unit at HUH, Bergen, Norway), measurement properties of the ECAS-N was evaluated. Study 3 (2016/2187 REK-Vest) is a prospective cohort stydy. The results are reported in two articles. The first article report the use of ECAS-N as a test to predict early changes in work ability and car driving. The second article report the use of ECAS-N as a test to predict the need for advanced therapy. Associations between clinical diagnosis of ALS-related dementia or not after three years and ECAS-baseline was evaluated. Study 4 (2016/2187 REK-Vest) is a qualitative interview study designed to better understand how cognitive impairment due to ALS influences close relations in everyday life. The protocol of study 1 and 2 was published in 2018. Results from study 1 was published in 2019 showing that the ECAS may have some advantages over other screening tests that have been used for assessing cognitive changes in ALS patients. However, recommendations for ALS-specific tests with sound psychometric properties are urgently needed. Study 2, part one was published in 2021. Here the Norwegian version of ECAS (ECAS-N) with age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance was provided. The ECAS-N holds promise for detecting cognitive and behavioural impairment in Norwegian patients with ALS and can be used in international research. However, cut-off scores are situational and could vary between cultures. Researchers should be aware of differences between tests applied in studies. For study 2, part two -Evaluation of reliability and validity of the ECAS-N, include 71 patients with ALS, 85 healthy control and 6 controls with Alzheimer’s disease. Primary outcome was the ECAS-N. Test-retest interval was four months. The Montreal Cognitive Assessement (MoCA) was used for evaluation of construct validity. Statistical analysis were Chronbach’s alpha for internal consistency, intraclass correlation coefficient (ICC), Cohens kappa, and Bland Altman plot for reliability. Construct validity was evaluated by testing a priori defined hypothesis. Dissemination of the results is in progress. In study 3, the ECAS-N is used in data collection for the prospective cohort study. Data collection for baseline is completed and include 31 patients with ALS. Dissemination of the results is in progress. In study 4, four patients and four carers were interviewed 8 months after diagnosis. Data were analysed by use of a thematically analysis. Results are presented in a Master thesis titled; Det har blitt et rollespill, which was defended at Oslo Metropolitan University (OsloMet) at 10th of December 2021. As the results are planned to be published in a scientific journal, the results are provisionally withheld from the public. Preliminary results was presented at the 7th Norwegian congress in Occupational Therapy, Stavanger 19.-21. 2022.

Cognitive impairment in ALS: screening tools, experiences and prognosisThe Edinburgh Cognitive and Behavioural ALS Screen is translated and culturally adapted into Norwegian (ECAS-N). Age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance is provided.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). A suitable screening tool in Norwegian is needed. Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is lacking. To gain knowledge, and a validate test for cognitive impairment in ALS, a multicentre project is carried out in four studies. Study 1 is a systematic review aimed to assess the properties of all measurements used in ALS and cognitive screening. Study 2 is twofold. In part one, the Edinburgh Cognitive and Behavioural ALS Screen is translated and culturally adapted into Norwegian (ECAS-N). In part 2, measurement properties of the ECAS-N is evaluated. Study 3 is a prospective cohort study to assess the use of ECAS-N as a test to predict early changes in work ability, car driving and the need for advanced therapy. Associations between clinical diagnosis of ALS-related dementia or not after three years and ECAS-baseline will be evaluated. Study 4 is a qualitative interview study designed to better understand how cognitive impairment due to ALS influences close relations in everyday life. The protocol of study 1 and 2 was published in 2018. Results from study 1 was published in 2019. For study 2, part 1 was published in 2021. Part 2 is in progress together with study 3 and study 4. Study 2 (2015/11598 and 2016/3166 - Data Privacy Unit at HUH, Bergen, Norway). Part 1-The Norwegian version of ECAS (ECAS-N) with age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance is provided. The ECAS-N holds promise for detecting cognitive and behavioural impairment in Norwegian patients with ALS and can be used in international research. However, cut-off scores are situational and could vary between cultures. Researchers should be aware of differences between tests applied in studies. Part 2-Evaluation of reliability and validity of the ECAS-N, include 71 patients with ALS, 85 healthy control and 6 controls with Alzheimer’s disease. Primary outcome was the ECAS-N. Test-retest interval was four months. The Montreal Cognitive Assessement (MoCA) was used for evaluation of construct validity. Statistical analysis were Chronbach’s alpha for internal consistency, intraclass correlation coefficient (ICC), Cohens kappa, and Bland Altman plot for reliability. Construct validity was evaluedte by testing a priori defined hypothesis. Data collection and data analysis are completed. Dissemination of the results is in progress. Study 3 (2016/2187 REK-Vest). Four patients and four carers were interviewed 8 months after diagnosis. Data were analysed by use of a thematically analysis. Results are presented in a Master thesis titled; Det har blitt et rollespill, which was defended at Oslo Metropolitan University (OsloMet) at 10th of December 2021. As the results are planned to be published in a scientific journal, the results are provisionally withheld from the public. Preliminary results is accepted for oral presentation at the 7th Norwegian congress in Occupational Therapy, Stavanger 19.-21. 2022. Study 4 (2016/2187 REK-Vest). The ECAS-N is used in data collection for the prospective cohort study. Data collection for baseline is completed and include 31 patients with ALS. Data analysis is in progress.

Cognitive impairment in ALS: Screening tools, experiences and prognosisRecommendations of ALS-specific tests with sound psychometric properties are urgently needed for clinical evaluation of patients as well as for researchers. The screening test Edinburgh Cognitive and Behavioural ALS Screen and the social cognition test Reading the Mind in the Eyes are recommended for assessing cognitive change in ALS patients.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is lacking. A suitable screening tool is not available in Norwegian. To gain knowledge, and validate tests for cognitive impairment in ALS, a multicentre project is carried out in four studies. 1) Validation of the translated Norwegian version of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS-N). 2) A prospective cohort study to assess the use of ECAS-N as a test to predict early changes in work ability, car driving and the need for advanced therapy. Associations between clinical diagnosis of ALS-related dementia or not after three years and ECAS-baseline will be evaluated. Study 1 and 2 are further described in more detail in the Protocol which is published in Contemporary Clinical Trials Communications 14 (2019). 3) A qualitative interview study, relying on interpretive description. Both patients and carers will be interviewed. 4) A systematic review to assess the properties of all measurements used in ALS and cognitive screening. A descriptive synthesis will guide a conclusion on which cognitive measurement is best suited for which purpose. Research activities from January to December 2020: Study 1 (2015/11598 and 2016/3166 - Data Privacy Unit at HUH, Bergen, Norway) and study 2 (2016/2187 REK-Vest) - The ECAS-N is used in data collection for the validation study (study 1) and the prospective cohort study (study 2). Sixty two participants are included in study 1 and 28 participants in study 2. Study 3 (2016/2187 REK-Vest) – So far, three patients and three carers are interviewed. Further analysis and publication will be in cooperation with a master student from Oslo Metropolitan University (OsloMet). Study 4 (PROSPERO registration number CRD42017055603) was published in Patient Related Outcome Measures in September 2020 Here, we provided a list of all tests used to assess cognitive change in patients with ALS and a descriptive synthesis of the psychometric properties of tests that were evaluated in a population of ALS patients. We concluded that the screening test ECAS and the social cognition test Reading the Mind in the Eyes (RME), may have some advantages over other tests that have been used for assessing cognitive change in ALS patients.

Cognitive impairment in ALS: screening tools, experiences and prognosisRecommendations of ALS-specific tools for optimal cognitive testing are urgently needed for clinical evaluation of patients as well as for researchers. Psychometric properties of the Norwegian version of "Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen" and its use as an early predictor for mental decline is evaluated.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is lacking. A suitable screening tool is not available in Norwegian. To gain knowledge, and validate tools for cognitive impairment in ALS, a multicentre project is carried out in four studies. 1) Validation of the translated Norwegian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS-N). 2) A prospective cohort study to assess the use of ECAS-N as a tool to predict early changes in work ability, car driving and the need for advanced therapy. Associations between clinical diagnosis of ALS-related dementia or not after three years and ECAS-baseline will be evaluated. 3) A qualitative interview study, relying on interpretive description. Both patients and carers will be interviewed. 4) A systematic review to assess the properties of all measurements used in ALS and cognitive screening. If applicable, a meta-analysis will guide a conclusion on which cognitive measurement is best suited for which purpose. Research activities from January to December 2019: Study 1 (2015/11598 and 2016/3166 - Data Privacy Unit at HUH, Bergen, Norway) and study 2 (2016/2187 REK-Vest) - The protocol is published in Contemporary clinical trials communications 14(2019). ECAS-N is used in data collection for the validation study (study 1) and the prospective cohort study (study 2). Fourtyfour participants are included in study 1 and 19 participants in study 2. For content validity in study 1, test scores are needed from patients with cognitive impairment related to the diagnosis of dementia. Patients with dementia (n=6) are recruited from Haraldsplass Deaconess Hospital (HDH). A cooperation agreement is signed between the project leader and HDH (2019/189-IAKK). Study 3 (2016/2187 REK-Vest) – So far, one patient and one carer are interviewed. Further analysis will be in cooperation with a master student from Oslo Metropolitan University (OsloMet). Study 4 (PROSPERO registration number CRD42017055603) – an updated search was conducted in December 2019 and analysis are completed.

Cognitive impairment in ALS: screening tools, experiences and prognosisRecommendations of ALS-specific tools for optimal cognitive testing are urgently needed for clinical evaluation of patients as well as for researchers. Psychometric properties of the Norwegian version of "Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen" and its use as an early predictor for mental decline is evaluated.Summary: Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is lacking. A suitable screening tool is not available in Norwegian. To gain knowledge, and validate tools for cognitive impairment in ALS, a multicentre project is carried out in four studies. 1) Validation of the translated Norwegian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS-N). 2) A prospective cohort study to assess the use of ECAS-N as a tool to predict early changes in work ability, car driving and the need for advanced therapy. Associations between clinical diagnosis of ALS-related dementia or not after three years and ECAS-baseline will be evaluated. 3) A qualitative interview study, relying on interpretive description. Both patients and carers will be interviewed. 4) A systematic review to assess the properties of all measurements used in ALS and cognitive screening. If applicable, a meta-analysis will guide a conclusion on which cognitive measurement is best suited for which purpose. Research activities from April to December 2018: Study 1 (2015/11598 and 2016/3166 - Data Privacy Unit at HUH, Bergen, Norway) and study 2 (2016/2187 REK-Vest) - A protocol has been submitted to the journal “Contemporary clinical trials communications” and is currently under review. The ECAS-N is used in data collection for the validation study (study 1) and the prospective cohort study (study 2). Thirty participants are included in study 1 and 18 participants in study 2; Study 4 (PROSPERO registration number CRD42017055603) - Preliminary results was presented at the International Symposium on ALS/MND in Glasgow, UK - 7-9 December 2018. In this presentation, we concluded that the use of a large number of varying assessment tools makes it difficult to compare results from different studies. Commonly used tools may be of limited utility to assess ALS-specific cognitive impairment. The use of comprehensive and time-consuming assessment may be a burden for the patients. Scarcity of assessment tools, which are sufficient, validated in ALS make it difficult to draw definite conclusions on the cognitive profile for the majority of patients. Recommendations of ALS-specific tools with sound psychometric properties are urgently needed in the interest of patients and researchers.

Cognitive impairment in ALS: screening tools, experiences and prognosisA translated Norwegian version of the Edinburgh Cognitive and Behavioral Amyotrophic lateral sclerosis Screen (ECAS) is used in data collection at four hospitals in Norway. A systematic review to assess the properties of all measurements used in ALS and cognitive screening, is registered in PROSPERO. A review of 5749 articles is in progress.Cognitive impairment is present in about 40% of all patients with amyotrophic lateral sclerosis (ALS). A suitable screening tool is not available in Norwegian. Knowledge in how cognitive impairment shall interfere on decision-making related to life-prolonging treatment, working capability and driving ability is lacking. The needs of those who suffer are also asked for. To gain knowledge, and validate tools for cognitive impairment in ALS, a multicenter project is carried out in four studies. 1) Validation of a translated Norwegian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS). 2) A prospective cohort study to assess the use of ECAS as an early predictor in decision making, especially related to life-prolonging treatment, working capability and driving ability. Associations between clinical diagnosis of dementia or not, after three years, until death or use of permanent ventilation support, and ECAS-baseline will be evaluated. 3) A qualitative interview study, relying on interpretive description. Patients and carers attributed meanings of living with cognitive impairment and expectations of health-care will be elaborated. 4) A systematic review to assess the properties of all measurements used in ALS and cognitive screening. If applicable, a meta-analysis will guide a conclusion on which cognitive measurement is best suited for which purpose. Activities from April to December 2017 A Norwegian multicenter study is anchored at Haukeland Univerisity Hospital, Bergen. It is organized as collaboration between the Department of Occupational Therapy, the Department of Neurology and the Competency Centre for Clinical Research. Collaboration due to data collection is established with the Clinic of Clinical Services, St. Olavs Hospital, Trondheim University Hospital, Trondheim, the Department of Social Worker, Occupational Therapy and Physiotherapy, Hospital of Southern Norway, Kristiansand and the Department of Physio- and Occupational Therapy, Medical Service Clinic, Namsos Hospital, Nord-Trøndelag Hospital Trust, Namsos. Study 1 and 2: Using international guidelines (Sousa & Rojjanasrirat, 2011) the ECAS have been translated into Norwegian. The translated Norwegian version of the ECAS has been approved by the copyright holder Dr. Sharon Abrahams and is used in data collection for the validation study (study 1) and the prospective cohort study (study 2). Twelve participants are included in study 1 and 7 participants in study 2. Study 4 is registered in PROSPERO (registration number CRD42017055603). Search for all time published research articles concerning the research question in any language have been conducted. The initial search extracted 5749 articles after duplication check. Of these, 5139 titles and abstracts were excluded, 610 articles received a full text review of which 354 were included in the study. A list of all measurement tools designed for assessing cognitive function and used in ALS-specific health-care are prepared and will form the basis of further systematic search of their psychometric properties.