Development and Validation of the Korean Version of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS-K)

- ^aDepartment of Neurology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea.
- ^bDepartment of Neurology, Seoul National University Hospital, Seoul, Korea.
- ^cDepartment of Neurology, Center for Hospital Medicine, Seoul National University Hospital, Seoul, Korea.
- ^dPeabody College of Education and Human Development, Vanderbilt University, Nashville, TN, USA.
- ^eDoo Neurology Clinic, Cheonan, Korea.
- ^fDepartment of Neurology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
- ^gDepartment of Neurology, Incheon Sejong Hospital, Incheon, Korea.
- ^hEuan MacDonald Centre for Motor Neurone Disease Research, Human Cognitive Neuroscience, School of Philosophy, Psychology and Language Science, University of Edinburgh, Edinburgh, UK.
- ⁱDepartment of Neurology, Seoul National University College of Medicine, Neuroscience Research Institute, Seoul National University Medical Research Council, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
Correspondence: Yoon-Ho Hong, MD, PhD. Department of Neurology, Seoul National University College of Medicine, Neuroscience Research Institute, Seoul National University Medical Research Council, Seoul Metropolitan Government Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea. Tel +82-2-870-2474, Fax +82-2-831-2826, Email: yhh@snu.ac.kr

Received October 20, 2022; Revised December 23, 2022; Accepted January 16, 2023.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Purpose

Cognitive and behavioral changes are common in amyotrophic lateral sclerosis (ALS), with about 15% of patients presenting with overt frontotemporal dementia and 30%–50% with varying degrees of impairments. We aimed to develop and validate the Korean version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS-K), a brief multidomain assessment tool developed for ALS patients with physical disability.

Methods

We developed the ECAS-K according to the translation guidelines, and administered it to 38 patients with ALS and 26 age- and education-level-matched controls. We also administered the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) to investigate convergent validity, and the Center for Neurologic Study-Liability Scale to assess the association between pseudobulbar affect and cognitive/behavioral changes.

Results

Internal consistency among the ECAS-K test items was found to be high, with a Cronbach’s alpha of 0.87. Significant differences were found between patients with ALS and the controls in language, fluency, and memory functions (p<0.05). Abnormal performance based on the ECAS total score was noted in 39.4% of patients, and 66.6% presented behavioral changes in at least one domain. Significant correlations were observed between the scores of the ECAS-K and those of other cognitive screening tools (MoCA and FAB, with correlation coefficients of 0.69 and 0.55, respectively; p<0.01).

Conclusions

We developed and validated the ECAS-K which could be used as an effective tool to screen the cognitive and behavioral impairments in Korean patients with ALS.

Keywords

amyotrophic lateral sclerosis; cognition; behavior

INTRODUCTION

Amyotrophic lateral sclerosis (ALS) is a fatal and heterogeneous neurodegenerative disease mainly involving the motor neurons of the brain and spinal cord,1, 2, 3 while cognitive and behavioral changes are reportedly common with about 15% of patients presenting with overt frontotemporal dementia (FTD) and 30%–50% with varying degrees of impairments.4, 5, 6 Screening and monitoring of the cognitive and behavioral impairments are clinically important since they are associated with shorter survival, increased caregiver burden, and impaired decision-making capacity.4, 7, 8, 9 Despite the significant implication for advance care planning, accurately assessing the cognitive and behavioral changes is challenging in practice because motor disabilities such as dysarthria and limb weakness may affect the performance in cognitive tests.

The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a brief multidomain assessment tool specifically developed for patients with ALS.10 It consists of ALS-specific (language, fluency, executive function, and social cognition) and nonspecific (memory and visuospatial) domains along with a separate caregiver questionnaire to assess behavioral changes and psychotic symptoms that are characteristic of FTD. The ECAS has been demonstrated to be effective in screening and identifying the specific profile of cognitive and behavioral changes in patients with ALS.11 It has been translated into 24 languages, with some of the translated versions having been validated.11, 12, 13, 14 This study aimed to develop the Korean version of the ECAS (ECAS-K) and evaluate its validity among patients with ALS.

METHODS

Participants

Patients with ALS and the controls between September 2020 and June 2021 were recruited from three general hospitals (Seoul National University Hospital, Seoul Metropolitan Government Boramae Medical Center, and Busan Paik Hospital). The inclusion criteria were as follows: 1) ALS diagnosis according to the revised El Escorial criteria,15 and 2) ability to communicate via either the spoken or written forms of the Korean language, with scores in the speech and handwriting subdomains of the ALS Functional Rating Scale–Revised (ALSFRS-R) of higher than 3 and 2, respectively. Patients were excluded if they were in the advanced stages of ALS, (i.e., unable to communicate in either spoken or written form), or if they had major psychiatric, medical, or other neurological diseases including overt dementia. The controls were recruited from age- and education-level-matched primary caregivers of the patients (spouse or siblings) who were screened through an interview to rule out any significant psychiatric/neurological diseases or cognitive issues. Disease severity was assessed using the ALSFRS-R.16

This study was approved by the local Institutional Review Boards (IRB No. 2005-017-1121) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent.

Korean version of the Edinburgh Cognitive and Behavioral ALS Screen

The ECAS is a brief (15–20 minutes) screening tool that includes the assessment of the following domains: fluency (free-words, restrained-words), executive functions (reverse digit span, alternation, inhibitory sentence completion, social cognition), language (naming, comprehension, spelling), memory (immediate recall, delayed percentage retention, delayed recognition), and visuospatial functions (dot counting, cube counting, number location) (https://ecas.psy.ed.ac.uk/). Spoken responses are preferred, but written responses are substituted in cases of marked dysarthria.

We developed the ECAS-K according to the translation guidelines (https://ecas.psy.ed.ac.uk/ecas-international/) with the permission of the original author. Verbal fluency scores were normalized according to the performance of 40 control subjects in the preliminary study in accordance with the ECAS guidelines (https://www.era.lib.ed.ac.uk/handle/1842/6592).

The original ECAS was translated into Korean and then back-translated into English by two neurologists (J.S.K. and Y.H.H.) and an independent researcher (E.C.) who was fluent in both languages.17 Some changes were made to account for language and cultural differences. The specifics of the modifications are listed in Supplementary Table 1 (in the online-only Data Supplement). The administration guide was also translated with reference to the ECAS Administration and Guidance Notes 2013 English version.

Other neuropsychological tests

We administered the Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB) in patients with ALS to investigate convergent validity.17, 18, 19 The Center for Neurologic Study-Liability Scale (CNS-LS) was used to assess pseudobulbar affect and its association with cognitive and behavioral changes in patients.

Procedures

The ECAS-K was administered in a quiet room, which took 20–40 minutes depending on the presence and severity of physical and cognitive impairments of the participants. After completing the ECAS-K, patients underwent additional tests including the MoCA, FAB, and CNS-LS. The caregiver interviews for behavioral changes were administered after the patients had finished the above tests, which took another 10–15 minutes.

Statistical analysis

Baseline characteristics are presented as mean±standard deviation (SD), median (interquartile range), or number (percentage) values depending on the variable type. Student’s t-test (or the Mann-Whitney test) was used for continuous variables, and the chi-square test was used for categorical variables, as appropriate. Cronbach’s alpha coefficient was estimated to assess internal consistency among the items of ECAS-K. The relationships between ECAS-K and other neuropsychological tests were evaluated using Spearman correlation analysis. The cutoff for the ECAS-K total score was defined as two SDs below the mean value for the controls. All analyses were performed using SPSS for Windows (version 25, IBM Corp., Armonk, NY, USA), and p<0.05 was considered significant.

RESULTS

The study included 38 patients with ALS (19 males and 19 females) and 26 age- and education-level-matched controls (10 males and 16 females). The demographic and clinical features of the participants are summarized in Table 1. There were no significant differences between patients and controls in age, education level, or sex distribution. The median disease duration was 17.5 months, and the mean ALSFRS-R total score was 37.5. Eleven patients (29%) had bulbar symptom onset. The level of diagnostic certainty according to the revised El Escorial criteria was clinically definite in 8 patients, clinically probable in 17, clinically probable laboratory-supported in 5, and clinically possible in 8. The level of diagnostic certainty in three of the eight patients with clinically possible ALS changed to clinically probable as the disease progressed. The clinical course in the other five patients was compatible with ALS with relentless progression and spread of motor weakness and atrophy.

Table 1
Demographic and clinical features of the participants

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Cronbach’s alpha coefficient for the ECAS-K was 0.87 overall (0.87 and 0.86 for the patient and control groups, respectively), indicating a high internal consistency between the test items. The ECAS-K total scores were found to be significantly correlated with age (r=-0.27, p=0.03) and education level (r=0.32, p=0.01) (Supplementary Table 2 in the online-only Data Supplement).

Normative data with abnormality cutoffs (based on two SDs from the mean) are presented in Table 2. Significant group differences were found between the patients and controls for the total scores as well as for the scores in most cognitive subdomains of the ECAS-K (Supplementary Table 3 in the online-only Data Supplement). After applying the abnormality cutoffs, 15 patients (39.4%) were in the abnormal range on the total score, 16 (42.1%) were impaired on the ALS-specific score, and 11 (28.9%) had ALS nonspecific scores below the cutoff (Fig. 1). The most frequently impaired cognitive subdomain was fluency (in 44.7%), followed by memory (26.3%), executive function (18.4%), and language (18.4%). None of the patients was impaired on visuospatial function.

Fig. 1
Performance of patients with ALS on the ECAS-K. The horizontal lines represent the abnormality cutoffs for each score (two SDs below the mean derived from age- and education-level-matched controls). Numbers and percentages of patients in the abnormal range are depicted for each score. ALS, amyotrophic lateral sclerosis; ECAS-K, Korean version of the Edinburgh Cognitive and Behavioral ALS Screen.

Table 2
Normative data on the ECAS-K scores in the abnormal range

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The convergent validity of the ECAS-K among patients with ALS was assessed using two standard cognitive screening tools (MoCA and FAB), which indicated significant correlations between the ECAS-K total score and both the MoCA (r=0.69, p<0.001) and FAB (r=0.55, p<0.001) (Fig. 2). As for the associations between cognitive impairment and other clinical parameters, there were no significant correlations between the ECAS-K total score and pseudobulbar affect (as measured by the CNS-LS; r=0.06, p=0.58), motor impairment (ALSFRS-R; r=-0.09, p=0.59), or disease duration (months from symptom onset; r=0.14, p=0.40).

Fig. 2
Correlations between the ECAS-K total score and other cognitive screening tools (MoCA and FAB) in patients with amyotrophic lateral sclerosis. ECAS-K, Korean version of the Edinburgh Cognitive and Behavioral ALS Screen; FAB, Frontal Assessment Battery; MoCA, Montreal Cognitive Assessment.

The behavior screen was completed by the primary caregivers of 27 patients. The frequency of behavioral changes across five domains is shown in Fig. 3. Overall, 18 patients (66.6%) presented behavioral changes in at least one domain. Apathy/inertia was the most common type of behavioral change (present in 15 patients, 55.6%), followed by loss of sympathy/empathy (n=9, 33.3%), disinhibition (n=4, 14.8%), perseverative/stereotype (n=3, 11.1%), and hyperorality/altered eating behavior (n=2, 7.4%) (Supplementary Table 4 in the online-only Data Supplement). Of those 27 patients, 16 (59.2%) presented behavioral changes across 2 domains meeting the criteria for ALSbi, and 3 patients (11.1%) in at least 3 domains meeting the criteria for possible behavioral-variant FTD. None of the caregivers reported psychotic symptoms.

Fig. 3
Frequency of behavioral impairment in patients with amyotrophic lateral sclerosis.

DISCUSSION

In this study, we present the Korean version of ECAS with some modifications to the original version for an adaptation to Korean language and culture. Supporting the validity of ECAS-K, our results demonstrated that the test items had high internal consistency and strong convergent validity with two traditional cognitive screening tools (FAB and MoCA). With the cutoff values derived from age- and education-level-matched controls, 39.4% of our patients were tested abnormal for the ECAS-K total score. Our results indicated that the proportion of subjects with impairment was higher in the ALS-specific subdomain (42.1%) than in the ALS nonspecific subdomain (28.9%), with impairment most frequently occurring in fluency (44.7%), followed by the memory (26.3%), executive (18.4%), and language (18.4%) functions.

Our results were overall consistent with previously reported data from Italy, China, and the UK.10, 12, 13, 14 The percentages of patients with ALS with abnormal ECAS total and ALS-specific scores were 37% and 36% in the Italian cohort, respectively, 35.7% and 42.8% in the Chinese cohort, and 29% and 29% in the UK cohort. Other clinical variables including pseudobulbar affect, motor impairment, and disease duration were not significantly correlated with the ECAS-K total score. Cognitive impairment may worsen with disease progression.20 However, disease duration may not necessarily be correlated with cognitive impairment, and our results were consistent with those of previous studies.13, 14 This might be explained by the variability of disease progression among patients and the cross-sectional study design. A longitudinal study is needed to detect progressive cognitive decline, and the use of alternate ECAS forms (ECAS-A, -B, and -C) might be useful for serial assessments in order to avoid practice effects.21

Our data were also consistent with those of previous studies regarding the prevalence and profile of behavioral impairments, with apathy being the most frequent behavioral change in our patients (55.6%) followed by loss of sympathy/empathy (33.3%). The frequency of behavioral impairments in a German-Swiss population were high in the domains of apathy and loss of sympathy/empathy (23% for both subgroups), with 30% of patients presenting behavior impairment in any domain. An Italian population also showed a similar profile, with the most common abnormalities in apathy followed by loss of sympathy/empathy (45% and 22%, respectively).12, 13, 14, 22

Differences in ALS genetic background appear to be an important factor in explaining racial differences in cognitive impairment rates and profiles. While C9orf72 mutations, the most common genetic cause of ALS in Caucasians, are frequently associated with cognitive impairment of the frontotemporal type, they are very rare in East Asians.23 On the other hand, SOD1 mutations, the most common genetic cause of ALS in Koreans, are known to be rarely associated with cognitive impairment, although a recent study involving an Italian cohort found that SOD1 mutations were more commonly associated with behavioral involvement than previously thought.24, 25 Given that gene therapy will gradually become a reality for ALS, further studies to elucidate the associations between gene mutations and cognitive and behavioral dysfunctions will have important implications for clinical trials and advance care planning.

We are conscious that our study has several limitations, mainly the failure to perform the formal cognitive test in control group and the rather restricted spectra of disease duration and motor impairment in patients with ALS that were biased toward the early stages and mild motor impairments, respectively. Although it would have been desirable, we could not perform formal cognitive tests on the spouses or siblings of the control participants due to practical constraints such as time and cost, and instead screened cognitive issues through an interview. This might have led to the proportion of control participants within the abnormal range for ALS nonspecific subdomain scores being higher than in previous studies (28.9% in our cohort vs. 6% in UK and 8.3% in Chinese cohorts). Since cognitive performance on the ECAS-K was significantly associated with age and education level, further studies with a larger number of cognitively normal controls should provide the age- and education-stratified cutoffs for the Korean population. Finally, since cognitive impairment may worsen with disease progression,20, 26 further studies involving a larger number of patients on a more-diverse spectrum of disease stages are warranted to characterize the cognitive and behavioral changes.

In conclusion, the present study has developed and validated the Korean version of ECAS in the present study. Our results suggest that the ECAS-K can be used as a screening tool to effectively assess cognitive and behavioral impairments in patients with ALS. Future studies need to derive age- and education-stratified cutoffs from a larger control group, and to characterize distinct cognitive phenotypes and longitudinal changes in patients with ALS.

Supplementary Materials

The online-only Data Supplement is available with this article at https://doi.org/10.3988/jcn.2022.0403.

Supplementary Table 1

Modifications in the Korean version of ECAS

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Supplementary Table 2

Correlations of ECAS-K total scores with age and years of education

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Supplementary Table 3

Performance of ALS patients and controls on ECAS-K

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Supplementary Table 4

Behavioral impairments in amyotrophic lateral sclerosis patients (n=27)

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Notes

Author Contributions:

Conceptualization: Jeeun Lee, Eric Cho, Jaeyoung Seo, Ji-Sun Kim, Jung-Joon Sung, Sharon Abrahams, Yoon-Ho Hong.
Data curation: Jeeun Lee, Ahwon Kim, Seok-Jin Choi, Eric Cho, Jaeyoung Seo, Seong-il Oh, Jinho Jung, Ji-Sun Kim.
Formal analysis: Jeeun Lee, Yoon-Ho Hong.
Investigation: Jeeun Lee, Seok-Jin Choi, Seong-il Oh, Jinho Jung, Jung-Joon Sung.
Methodology: Jeeun Lee, Ji-Sun Kim, Jung-Joon Sung, Sharon Abrahams, Yoon-Ho Hong.
Project administration: Jeeun Lee, Ahwon Kim, Seong-il Oh, Jinho Jung, Yoon-Ho Hong.
Resources: Jeeun Lee, Ahwon Kim, Seong-il Oh, Jung-Joon Sung, Yoon-Ho Hong.
Supervision: Jung-Joon Sung, Yoon-Ho Hong.
Validation: Yoon-Ho Hong.
Visualization: Jeeun Lee, Sharon Abrahams.
Writing—original draft: Jeeun Lee.
Writing—review & editing: Jeeun Lee, Seong-il Oh, Yoon-Ho Hong.

Conflicts of Interest:The authors have no potential conflicts of interest to disclose.

Funding Statement:This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1F1A1072153).

Availability of Data and Material

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

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