Measuring Cognitive and Behavioural Change in ALS
Research type
Research Study
Full title
Cognitive and behavioural impairment in Amyotrophic Lateral Sclerosis: Comparing measures and validating revised consensus diagnostic criteria for Amyotrophic Lateral Sclerosis-Frontotemporal Spectrum Disorder
IRAS ID
240593
Contact name
Laura Goldstein
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
2 years, 11 months, 30 days
Research summary
Research Summary
About 50% of people with Amyotrophic Lateral Sclerosis (ALS) (also known as Motor Neuron Disease (MND)) develop changes in their thinking and behaviour which may, in around 15% of cases, lead to the diagnosis of frontotemporal dementia (FTD). Several different assessment methods - called screening tools – exist for testing people with ALS and obtaining information from carers in clinic/at home. However, it is unclear whether each of the different tools would lead to the same conclusion in the same person with ALS, since they use different approaches and have different rules for deciding whether someone is impaired. If they do not agree, some people could receive an incorrect diagnosis of changes in their thinking, language and behaviour, depending on which tool was used; this might affect the practical care they receive. Thus, the main aim of this project is to test whether different screening tools lead to similar rates of diagnosed change in the same people. We will test this by giving three screening tests measuring thinking and language to about 114 people with ALS. About 91 people who know the person with ALS well will complete sets of questions about any change in the behaviour of the person with ALS. We can then examine differences in how these measures detect thinking and behaviour change. The people with ALS and about 100 healthy controls (similar to the people with ALS in age, gender and education) will also complete other measures of thinking and language so we can i) compare how each screening measure compares to a common set of measures of thinking and language, ii) determine which is the best screening test of thinking and behaviour changes in people with ALS and iii) inform clinicians and researchers about the implications of using different measures in their clinical work and research.
Summary of Results
The main aim of this study, which was funded as a PhD studentship by the Motor Neurone Disease Association, was to compare the ability of relatively quick screening assessments to identify cognitive (that is, thinking and language) changes (3 task-performing screens) or behavioural changes (5 questionnaire-like screens) in people with Amyotrophic Lateral Sclerosis (ALS; a life-limiting disease, also known and Motor Neurone Disease) and determine which screen is the best to use and why. This is important because it has been shown that as many as 50% of people with ALS may show changes in their thinking abilities and/or their behaviour, and this can have an impact on them and their families and the care that they receive.
The cognitive assessment screens that we evaluated were the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), the ALS Cognitive and Behaviour Screen (ALS-CBS) and the Mini- Addenbrooke’s Cognitive Examination (Mini-ACE). The behavioural screening tests were the questionnaires measuring changes in behaviour from the ECAS and the ALS-CBS as well as the Beaumont Behavioural Inventory (BBI), the ALS Frontotemporal Dementia Questionnaire (ALS-FTD-Q) and the Motor Neuron Disease Behavioural Instrument (MiND-B). We investigated which of these screens was best at differentiating between people with ALS who had cognitive or behavioural changes or had none of these symptoms.
The research aims were broadly met but were modified during the research period because of the effect of the COVID-19 pandemic, which halted face-to-face assessments in March 2020, and limited the number of participants we could recruit. Therefore, we modified the project and also assessed how well remote versions of the screens performed; remote versions were administered via computers using video call software or as online questionnaires. Although we had hoped to recruit ~114 people with ALS, ~99 informants of people with ALS and ~100 healthy controls when people were tested face-to-face, the pandemic lockdowns meant that we could not achieve this level of recruitment. In the end we recruited 41 people with ALS, 35 informants and 41 healthy controls for face-to-face testing (before recruitment was stopped by the first lockdown). We also recruited 57 people with ALS, 49 informants and 44 healthy controls for remote testing during the remainder of the project. The samples were not completely well-matched, and this had to be accounted for in the analyses. The reduced sample size prevented us from undertaking a specific type of statistical analysis (Latent Trait analysis) but we did undertake other statistical analyses of the data, and were able to combine data from face-to-face testing and remote testing for most of our analyses.
We were able to identify the best measure for identifying cognitive changes and to identify the better measures for identifying behavioural changes in people with ALS. Additionally, remote versions of cognitive and behavioural measures were either found to work like the original in-person versions or we were able to suggest adjustments so that they could be used instead of the original in-person versions. The online questionnaire versions of the behavioural screening tools function similarly to written paper questionnaire versions of the screening tools. However, there was evidence that the remote versions of the cognitive screening tools may not function exactly like the in-person, face-to-face versions. Therefore, if cognitive screens are used remotely, they should have their own score, specific to only the remote version, that indicates whether someone has cognitive impairment or not.
We found that the ECAS was the best measure for screening for cognitive impairment in people with ALS. It was the best at differentiating between people with and without cognitive impairment and was also the most suitable for administering to people who have dysarthria (motor speech impairments) or muscle wasting in the arms and hands. The best behavioural screening tool for people with ALS was less clear. The BBI performed the best in terms of its ability to predict and be predicted by other behavioural screening tools. However, it may be less practical than the other screening tools because it takes longer to complete.
We also found that cognitive and behavioural change in the person with ALS predicted distress (measured by a combination of anxiety, depression and perceived burden relating to caring) in the person who had rated the behavioural change in the person with ALS in our study. We also found that behavioural change had more impact than cognitive change (when behavioural change was measured by the MiND-B and cognitive change by the ECAS).The results from our study were consistent with our review of published data by other researchers concerning the screening tests, whereby the ECAS had most data in support of its use for cognitive testing, and the BBI and ALS-FTD-Q were found, on the basis of published literature, to have most data supporting their use when rating behaviour change in people with ALS.
The benefits of the study are that clinicians will now be able to select cognitive and behavioural screening measures knowing more about their strengths and weaknesses. Additionally, this study has determined that remote versions of the cognitive and behavioural screening tools are useful. People with ALS may be tested for cognitive and behavioural changes remotely in their own homes in the future. This may save them time and money from travelling to NHS sites and enable them to stay relaxed while at home.
As a result of the pandemic, and its potential impact on the lives of people with ALS, we also undertook a sub-study. An online interview study of spouses of people with ALS, who had taken part in the studies above, was introduced in following lockdowns. It allowed us to hear that while behavioural change in a small number of the people with ALS had occurred during the COVID-19 lockdowns, it had not made caring for these people more difficult. In terms of behavioural deterioration, the most reported behaviour change was an increase in apathy (i.e., lack of interest, enthusiasm, or concern; known to be the most common behavioural change in people with ALS) but loss of insight and egocentric (i.e., self-centred) behaviour in people with ALS were also reported. Spouses did not believe that the pandemic had affected behavioural deterioration but made have made it more apparent since not all normal activities could be undertaken, and the person with ALS may not have been interested in doing something new or different (i.e., they were apathetic).
In addition, remote hospital appointments had been mostly well-received with references being made to the reduction in costs, stress and time associated with travelling to appointments.Perhaps the most salient finding was that the lockdowns deprived people with ALS of the opportunity to pursue activities while still physically able to undertake these. An interaction between pandemic lockdown restrictions and physical deterioration caused by ALS was reported by spouses. This interaction led to a sense of loss of time whereby the pandemic restrictions prevented people with ALS experiencing life-enriching activities while they continued to physically deteriorate, to the extent that when restrictions were lifted, they were then unable to participate in those life-enriching activities.
The same disproportionate effect of the pandemic on social participation was reported by the spouses when talking about themselves. Spouses reported feelings of loneliness, a desire for an increase in social interaction, and anxiety over being infected with COVID-19 or the person with ALS being infected with COVID-19. They also reported increases in caregiving duties and a reduction in support and opportunities to take a break from the caring role. They reported an increase in caregiver burden.
Some spouses reported that they did not notice the effect of pandemic lockdowns because they felt that their lives were already heavily restricted by the limitations of ALS. For example, spouses reported not being able to eat at restaurants because the person with ALS could not, and not being able to visit relatives or go on holiday because the person with ALS could not travel.
Our results are currently being written up to be submitted as a PhD thesis by Lyndsay Didcote, and will be written up for publication in peer-reviewed journals. Some data has already been presented in online conferences. Since it is likely that the great majority of the people with ALS who participated in the studies here may well already have died, due to the poor prognosis associated with ALS, we do not wish to write to them or their caregivers in case we cause distress. Instead, we will be disseminating our results via a research newsletter and blog hosted by the Motor Neurone Disease Association. The timing of the publication of this blog is under the control of the Motor Neurone Disease Association but we have submitted draft text to them.
REC name
London - Dulwich Research Ethics Committee
REC reference
18/LO/1257
Date of REC Opinion
16 Nov 2018
REC opinion
Further Information Favourable Opinion