Determining impairment in the Swedish, Polish and German ECAS: the importance of adjusting for age and education

Abstract

Objective: Age and years of education are strong predictors of cognitive performance in several versions of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) and cutoffs for the Swedish and Polish versions are not established yet. Here we evaluated the performance of healthy subjects on the national versions of the Swedish and Polish ECAS and compared cognitive performance on three European translations of the ECAS. Methods: The ECAS performances of healthy subjects from Sweden (n = 111), Poland (n = 124) and Germany (n = 86) were compared. Based on the test results on the national versions of ECAS, age- and education-adjusted cutoffs were compared for the German, Swedish and Polish versions, respectively. Results: Age and years of education correlated with performance in the ECAS. Swedish subjects under the age of 60 years and Swedish subjects with low education level scored significantly higher in memory than the respective German and Polish subgroups. German and Polish subjects over 60 years of age performed significantly better in language than the respective Swedish subgroup. The Polish cohort in total had lower executive scores compared to the Swedish cohort, and lower than the German subjects in the higher education subgroup. Conclusions: The results highlight the importance of establishing age- and education-adjusted ECAS cutoffs not only in general, but also for seemingly similar populations of different origins. The results should be taken into account when comparing cognition data across patient populations including in drug trials where an ECAS test result is being used as an inclusion criterium or outcome measure.

Keywords:

• ALS
• FTD
• ECAS
• cognition test
• population differences

Introduction

Amyotrophic lateral sclerosis (ALS) is now recognized as a heterogenous syndrome with multiple genetic and clinical subtypes (1), including cognitive impairment in up to 50% of subjects, which may present as full-scale fronto-temporal dementia (FTD) in a subset of 5–15% of ALS patients (2,3). Mutations in more than 40 genes have been associated with causing ALS and several of these genes have been shown to be pleiotropic for a number of other neurological conditions, most notably the FTD spectrum (4). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) was specifically developed to assess the cognitive and behavioral profile of ALS patients, and to detect impairments in language, verbal fluency and executive functioning, subsumed under ALS specific functions, as well as impairments in memory and visuospatial functions, subsumed under ALS nonspecific functions (5). The ECAS has been translated into more than 20 languages (6) and has become the main instrument to quickly assess the overall cognitive performance of patients with suspected ALS in clinical practice and research studies (7–9; see also https://ecas.psy.ed.ac.uk/, last accessed on 19th January 2023), and is also used as outcome measure in drug trials (7,8). While some translations and normative data of language cohorts have a single general cutoff for their respective ECAS version, (5,9–15) cutoffs of other adaptions were stratified according to the chronological age and duration of school education (16–21) as these factors had been demonstrated to be strong predictors of cognitive performance (16,17). This resulted in an establishment of four cutoffs in each of these studies – for lower/higher level of education and for younger/older age (16–21). While cutoffs have been determined for several European populations (5,9,10,13,15–20), cutoffs for the Swedish and Polish version of the ECAS have not been published yet. We aim to close this gap and therefore evaluate the cognitive performance of healthy subjects on both versions to define general and, if applicable, age- and education-adjusted cutoffs for the Swedish and the Polish ECAS.

Furthermore, we aim to compare the performances of three European control populations on their respective ECAS version. There are substantial differences with regards to ECAS cutoffs between countries, e.g. almost 15 points between UK and German version (UK ECAS Total score cutoff = 105; German ECAS Total score cutoff = 90.7), which is why we began to wonder if some of the differences in cognition between ALS patients cohorts may be unrelated to ALS but may be explained by national differences in education systems, culture, religion and possible other factors. A comparison between Chinese and German control cohorts showed that there were only differences in the ECAS score for spelling, with the Germans performing worse (22). One explanation was that the language part was particularly different between both ECAS versions due to the very different alphabets and thus the difference in spelling between the cohorts may be due to the translation of the ECAS (23). So, when comparing the performance in three European versions of the ECAS, we would not expect any differences either, since we can assume that the language and culture are more similar in this case than when comparing western and eastern Asian countries, and therefore state the null hypothesis that there would be no significant differences across the populations. However, there are differences across European countries regarding length and system of education, lifestyle factors, physical and occupational activity and economic conditions which may affect cognitive aging and hence the cognitive performance relative to chronological age (23–26). We here present a head-to-head comparison of cognitive performances of healthy individuals in Germany, Poland and Sweden using earlier established national versions of ECAS to evaluate if there are differences in cognitive performance between different language cohorts of European decent.

Methods

Participants

To establish cutoffs for the Swedish and Polish version of the ECAS, healthy subjects were recruited in Sweden and Poland and examined with their respective ECAS version. For the comparison of cognitive performance of three populations of European decent on the ECAS, the Swedish and Polish cohort was compared with each other and additionally to a German cohort, which was used to establish the German age- and education-adjusted ECAS cutoffs and have been reported earlier (16).

The study was approved by the relevant ethics committees in Germany, Poland and Sweden adhering to the ethical standards of the Declaration of Helsinki of 1964 with later amendments. All participants gave written informed consent prior to the interviews. All participants were native speakers of the respective language and were without a history of psychiatric or neurological disease (except for headache) or learning difficulties. None of the test subjects had a family history of ALS or FTD.

The Swedish cohort consisted of 111 (71 females, 40 males) healthy native Swedish-speaking subjects with a mean age of 61.3 (SD = 14.3) years and mean years of education of 13.8 (SD = 2.8). Recruitment was made by public advertising for test subjects and efforts were made to make it as random and diverse as possible (e.g. members of a golf club, staff at the police academy, relatives of hospital staff etc.). All completed the oral version A 1.3 of the Swedish ECAS, available at https://ecas.psy.ed.ac.uk/ecas-international/#Swedish (last accessed on 19th January 2023).

The Polish cohort consisted of 124 (65 females, 59 males) healthy native Polish-speaking individuals with a mean age 59.3 (SD = 12.1) years and mean years of education of 14.0 (SD = 3.7). Recruitment was through personal communication with e.g. accompanying persons of patients with unrelated benign conditions at the out-patient clinic, family members of auxiliary hospital staff, members of a village club etc. Fifty-eight subjects were assessed with the written ECAS version and 66 individuals were assessed with the spoken version. The Polish version of ECAS is available at https://ecas.psy.ed.ac.uk/ecas-international/#Polish (last accessed on 19th January 2023).

The German cohort consisted of 86 healthy individuals (41 females, 45 males) with a mean age 56.6 (SD = 13.9) years and a mean years of education of 13.1 (SD = 2.6). Recruitment was through personal communication with e.g. accompanying persons of patients, visitors and staff of the clinics (16). Forty-eight subjects were assessed with the oral and 38 individuals were assessed with the spoken version (16), a summary of the performance on the ECAS and the previously reported cutoffs are presented in Table 1. The German version of ECAS is available at http://www.ecas.network (last accessed on 19th January 2023), the procedure of translation, standardization and validation have been reported before (27).

Table 1 Performance on the ECAS and age- and education-adjusted cut-offs of the German language cohort (as previously reported by Loose et al. (19)).

	All participants	Age- and education adjusted groups
	Mean (SD)	Cutoffs(19)
		Age <60, education ≤12 years	Age <60, education >12 years	Age ≥60, education ≤12 years	Age ≥60, education >12 years
	N = 86	n = 20	n = 26	n = 20	n = 20
ECAS total	111.80 (10.57)	93.5	99.7	78.8	98.2
ECAS ALS specific	82.55 (9.66)	56.3	84.5	56.4	73.9
ECAS ALS nonspecific	28.64 (3.50)	22.4	22.6	20.1	22.6
memory	16.89 (3.41)	11.0	10.8	8.8	10.6
visuospatial	11.76 (0.51)	10.2	11.4	10.4	11.5
language	26.65 (2.10)	23.1	26.3	18.6	25.3
fluency	19.09 (3.39)	11.4	9.9	13.6	17.1
executive function	38.78 (4.66)	32.5	34.9	24.8	30.0

ECAS: Edinburgh Cognitive and Behavioural ALS Screen.

ECAS ALS specific score includes language, fluency and executive functions.

ECAS ALS non-specific score includes memory and visuospatial functions.

ECAS Swedish and Polish versions

The original English version of the ECAS was initially translated to Swedish by team members trained in psychology and familiar with idiomatic expression of the Swedish language in accordance with established guidelines (28). This initial Swedish version 1.0 was reviewed by an external reviewer at CBG Consultancy (www.CBG.com), to compare the forward translation with the original English version, resulting in version 1.1. Blinded back-translation was then made by a bilingual linguist and compared to the original English version for consistency, resulting in version 1.2. In the following years some adjustments were made including another round of translation check by Otilingua International (www.alphatrad.com), resulting in the present version A 1.3. Table 2 summarizes the changes made to account for language and cultural differences. The ECAS interviews were performed by trained health professionals, a licensed psychologist and a last year psychology student at university, in a private setting either in the subject’s residence or in the hospital research unit. Only the test person and the interviewer were present in the room. An intellectual property right agreement for preparing and using a Swedish version of ECAS was signed between the University of Edinburgh and University of Umeå.

Table 2 Changes made to the ECAS to adapt to the Polish and Swedish cultures and languages.

	English version	Swedish version	Polish version
Memory – recall	Primrose Woods	Granskogen	Las Kabacki
	Douglas Watt	Anders Larsson	Tomasz Bąk
	Woodland project	N/A	przedsiębiorstwo Lasy Państwowe (national woods company)
	…impressed and especially proud…	N/A	…mile zaskoczony i dumny… (…positively surprised and proud..)
Language – spelling	Skateboard	Rullskridskor (roller skates)	N/A
	Biscuit	Choklad (chocolate)	N/A
	Brought	Definiera (to define)	N/A
Free fluency	Letter S	N/A	Letter K
Restricted fluency	Letter T	Letter P	Letter M
Executive – sentence completion	When she got up in the morning the sun was…(Instruction)	Dagen efter festen var lägenheten… (The day after the party, the apartment was…)	N/A
	John cut his hand with the sharp…orange (Instruction)	N/A	Adam przeciął sobie rękę ostrym…pomidorem (Adam cut his hand with the sharp…tomato)
	Sally spread her toast with butter and…	Sara bredde sin smörgås med… (On her toast, Sara spread…)	Hania…
	John…	Johan…	Zygmunt…
	She dived into the swimming…	Hon åkte till flygplatsen för att… (She went to the airport in order to…)	Zanurzyła się w ciepłej… (She dived in warm….)
	…to a local cafe…	…in på restaurangen… (…in the restaurant…)	…do miejscowego baru… (…to a local bar…)
Memory – delayed recall	Was he from the local council?	Pratade han med lokala fotografer? (Did he speak with local photographers?)	N/A
	Was his first name “Thomas”?	Var hans förnamn Göran? (Was his first name Göran?)	Czy na imię miał Stefan? (Was his first name Stefan?)

The original English version of the ECAS was initially translated to Polish by two team members trained in neurology/psychology, experienced in bilingual test translations and familiar with idiomatic expression of the Polish language in accordance with established guidelines (28). During the preparation of the initial version, details were consulted with a cognitive neuroscientist and one of the authors of the original English version (THB) (5), bilingual in English and Polish. The complete Polish translation was then reviewed by an external reviewer, to compare the forward translation with the original English version. The back-translation from Polish to English was then made by a bilingual linguist and compared to the original English version for consistency. After a pilot study of n = 10 healthy individuals, some adjustments were made in wording of instructions resulting in the present version. Table 2 summarizes the changes made to account for language and cultural differences. An intellectual property right agreement for preparing and using a Polish version of ECAS was signed between University of Edinburgh and Medical University of Warsaw.

For all three language versions of the ECAS, the conversion table for the verbal fluency index was adapted for populations according to the ECAS guidelines for translation (5). To adapt to the respective languages, letters for free and restricted fluency were changed (for Swedish and Polish see Table 2; for German see Lulé et al., 2015 (29)) to provide a comparable search space as the chosen letters for English speakers in the original ECAS.

Cutoff scores

In accordance with Abrahams et al. (5), cutoff scores were determined by subtracting two standard deviations from the mean score for different age- and education adjusted groups, as established earlier (16,27). Mandatory education in Sweden is 9 years of primary and secondary school, often followed by another 3 years of high school, while mandatory education in Poland is 8 years of primary school and 4 years of secondary school. To account for the differences in education systems, classification of education years for the Swedish and Polish cohorts was ≤12 years and >12 years, analogous to the International Standard Classification of Education – ISCED 3, which was also established for the German cohort (16). For age adjusted cutoff scores, a median split was performed for the Swedish and Polish cohorts, as was originally done for the German cohort (16). This resulted in a cutoff of ≤65 years for the younger subgroup and a cutoff of >65 years for the older subgroup for the Swedish cohort, which also fits the higher age of Swedish ALS patients compared to German and Polish patients (30) and also reflects the higher life expectancy of Swedes overall. The Polish cutoff for the age subgroups was ≤61 and >61 years.

Hence, four different cutoff scores were calculated for lower/higher level of education and for younger/older age, respectively.

Statistics

Data distribution was tested with the Kolmogorov-Smirnov test, which revealed non-normal distribution of ECAS scores, for age and for education. Non-parametric Mann-Whitney-U-tests were applied to compare the performance on the oral and written versions of the Polish and German ECAS, the statistical level of α = 0.05 was corrected with the Bonferroni-Holm method for eight comparisons each, which revealed no differences between the performance on the oral and the written versions.

Non-parametric Spearman correlations were used for the relationship between age and years of education with the ECAS, the p-value was corrected via Bonferroni-Holm method for 16 comparisons for each the Swedish and Polish cohort. Possible performance differences between sexes were considered using non-parametric Mann–Whitney-U-tests, also corrected via Bonferroni-Holm method for eight comparisons for each the Swedish and Polish cohort. Also, non-parametric Kruskal–Wallis-tests were applied to compare cognition between total language cohorts with post-hoc-testing for pairwise comparison, and then also for younger and older age-group and for groups of less and more years of education. p-values were corrected via Bonferroni-Holm method for 40 comparisons, the post-hoc tests were corrected via Bonferroni-Holm method for 40+(significant tests ×3) comparisons. Cohen’s d was used as effect size parameter with 0.2, 0.5, and 0.8 as thresholds for a small, medium, and large effect, respectively.

Results

Swedish ECAS and demographics

Age correlated significantly with the ECAS total score (r(109) = −0.34, p = 0.004), the ALS-nonspecific score (r(109) = −0.41, p < 0.001), and memory (r(109) = −0.40, p < 0.001). Years of education correlated significantly with the ECAS total score (r(109) = 0.28, p = 0.036) and the ALS-specific score (r(109) = 0.32, p = 0.009). All reported p-values are Bonferroni-Holm-adjusted for 16 comparisons. There were no differences in ECAS performance between sexes. Swedish ECAS cutoff scores are listed in Table 3.

Table 3 Cut-offs for the Swedish ECAS for the total cohort and stratified for age and education.

	All participants		Age- and education adjusted groups
			Cutoffs
	Mean (SD)	Cutoffs	Age ≤65, education ≤12 years	Age ≤65, education >12 years	Age >65, education ≤12 years	Age >65, education >12 years
	N = 111		n = 13	n = 44	n = 21	n = 33
ECAS total	115.23 (9.35)	96.53	96.43	103.60	89.44	94.96
ECAS ALS specific	84.50 (7.22)	70.07	66.62	74.18	66.78	69.64
ECAS ALS nonspecific	30.74 (3.82)	23.10	27.28	26.77	19.49	21.25
Memory	18.84 (3.76)	11.33	15.60	15.07	7.32	9.69
Visuospatial	11.80 (0.44)	10.91	11.10	11.24	10.59	10.69
Language	26.30 (1.98)	22.34	22.34	23.45	22.07	21.35
Fluency	19.60 (2.39)	14.82	12.22	17.14	11.86	15.76
Executive function	38.59 (5.46)	27.68	24.38	30.38	25.45	27.34

ECAS: Edinburgh Cognitive and Behavioral ALS Screen.

ECAS ALS specific score includes language, fluency and executive functions. ECAS ALS non-specific score includes memory and visuospatial functions.

Polish ECAS and demographics

Age correlated significantly with the ECAS total score (r(122) = −0.46, p < 0.001), the ALS-specific score (r(122) = −0.50, p < 0.001), language (r(122) = −0.29, p = 0.015), and executive functioning (r(122) = −0.52, p < 0.001). Education correlated significantly with the ECAS total score (r(122) = 0.27, p = 0.022), the ALS-specific score (r(122) = 0.25, p = 0.044), language (r(122) = 0.25, p = 0.044) and fluency (r(122) = 0.33, p < 0.001). All reported p-values are Bonferroni-Holm- adjusted for 16 comparisons. There were no differences in ECAS performance between sexes. Calculated cutoffs are listed in Table 4.

Table 4 Cutoffs for the Polish ECAS for the total cohort and stratified for age and education.

	All participants		Age- and education adjusted groups
			Cut-offs
	Mean (SD)	Cut-offs	Age ≤61, education ≤12 years	Age ≤61, education >12 years	Age >61, education ≤12 years	Age >61, education >12 years
	N = 124		n = 19	n = 43	n = 32	n = 37
ECAS total	111.58 (10.70)	90.18	92.87	99.55	82.27	91.34
ECAS ALS specific	82.72 (8.55)	65.62	69.72	73.15	58.52	66.58
ECAS ALS non-specific	28.86 (3.99)	20.88	18.65	22.61	19.95	20.17
Memory	17.54 (3.47)	10.60	8.73	12.50	11.14	8.92
Visuospatial	11.32 (1.28)	8.76	7.81	10.31	7.55	9.26
Language	26.98 (1.55)	23.88	25.04	25.47	21.75	24.55
Fluency	19.95 (2.64)	14.67	14.08	16.29	13.90	14.38
Executive function	35.79 (6.85)	22.09	25.96	27.42	16.84	22.19

Comparison of ECAS performance

The comparison of language cohorts revealed group differences in the ECAS ALS nonspecific section (H(2) = 26.23, p < 0.001, d = 0.57), memory (H(2) = 23.12, p < 0.001, d = 0.53), and executive function (H(2) = 15.05, p < 0.018, d = 0.42) (Figure 1). In post-hoc tests, the Swedish cohort scored higher in memory and consequently in the ALS nonspecific section compared to the German (memory: z = 4.56, p < 0.001, d = 0.69; ALS nonspecific: z = 4.61, p < 0.001, d = 0.70) and Polish (memory: z = 3.52, p = 0.021, d = 0.48; ALS nonspecific: z = 4.18, p < 0.002, d = 0.58) cohorts (Figure 1). These differences were most evident in the younger subgroup of the Swedish cohort compared to the younger German subgroup (memory: z = 5.05, p < 0.001, d = 1.15; ALS nonspecific: z = 5.00, p < 0.001, d = 1.13) and younger Polish subgroup (memory: z = 4.02, p = 0.003, d = 0.79; ALS nonspecific: z = 4.19, p = 0.002, d = 0.83), and also for the Swedish subgroup with lower educational level compared to the German subgroup with lower educational level (ALS nonspecific: z = 3.82, p = 0.007, d = 0.99).

Figure 1 Comparison of performance on the ECAS of healthy cohorts in Sweden (n = 111), Germany (n = 86) and Poland (n = 124). Box plots illustrate the median and interquartile range (IQR), whiskers represent the minimum and maximum values that are not outliers. Circles represent mild outliers (1.5 × IQR below first quartile or above third quartile), stars represent extreme outliers (3.0 × IQR below first quartile or above third quartile). p-Values refer to post-hoc comparisons between language cohorts and are Bonferroni–Holm corrected.

The overall Swedish cohort performed better than the Polish cohort regarding executive functioning (z = 3.49, p = 0.023, d = 0.48, Figure 1), whereas the Polish cohort performed better in language (z = −3.44, p = 0.027, d = 0.47). Differences in executive functioning were most prominent in the respective older subgroups, where the Swedish subgroup scored higher than the Polish subgroup (z = 4.21, p = 0.001, d = 0.82). Differences in language were shown for a higher educational level, where the respective Polish (z = −3.63, p = 0.015, d = 0.62) and German (z = −3.79, p = 0.008, d = 0.73) subgroups scored higher than the Swedish subgroup.

Differences between the German and Polish cohort could only be found regarding executive functioning for the higher educational level, with the German subgroup scoring higher (z = 3.46, p = 0.025, d = 0.67).

For all post-hoc tests, p-values were corrected via Bonferroni-Holm method for 70 comparisons.

Both the Swedish and Polish cutoffs are rather high when compared to a number cutoffs for some other language cohorts, but comparable to the level of the English, Italian, and Dutch versions (Table 5).

Table 5 Overview of cut-offs for different national versions of ECAS.

Language	ECAS total score	ECAS ALS-specific score	ECAS non-specific score	n
English (original) (5)	105	77	24	40
English (revised British) (19)	(100, 98, 110, 108)	N/A	N/A	80
Italian (17)	(92, 89, 108, 107)	(71, 64, 79, 79)	(24, 22, 27, 26)	248
Dutch (18)	(97, 89, 107, 102)	(71, 64, 78, 75)	(23, 22, 26, 23)	690
Swedish (this report)	(96, 89, 104, 95)	(66, 67, 74, 69)	(27, 20, 26, 21)	111
Polish (this report)	(93, 82, 96, 91)	(69, 59, 73, 67)	(19, 20, 23, 20)	124
Greek (9)	93	68	23	52
Norwegian (10)	92	65	24	85
German (16)	(93, 78, 99, 98)	(56, 56, 84, 73)	(22, 20, 22, 22)	86
English (Ireland) (20)	(96, 76, 100, 95)	(70, 57, 73, 68)	(23, 15, 24, 25)	82
Afrikaans (21)	(90, 78, 100, 85)	(65, 57, 74, 63)	(20, 18, 24, 20)	108
Persian (11)	88	61	23	31
English (South Africa) (21)	(95, 74, 95, 84)	(66, 50, 69, 68)	(18, 19, 22, 14)	53
Japanese (12)	86	65	16	28
Czech (13)	86	61	23	102
isiXhosa (21)	(76, 72, 91, 87)	(59, 54, 69, 63)	(14, 12, 18, 20)	100
Chinese (14)	81	58	19	84
Spanish (15)	73	53	19	40

Parentheses designate subgroup cut-offs, the order is: younger and less education, older and less education, younger and high education, older and high education.

Discussion

Since its introduction in 2014, the ECAS has become a valuable tool as part of the global assessment of ALS/FTD patients not only for optimizing the personalized clinical management of a patient, but also as an outcome measure in a range of research studies (7,8,29,31,32). As previously shown for a number of language adaptations (16–21), age and education correlated significantly with performance also in the Polish and Swedish ECAS’s. In summary, the younger the participant the better the performance; also, the higher the education level the better the performance. These findings strengthen the importance of establishing age- and education-adjusted cutoffs (Table 5), which we presented here for the Polish and Swedish versions of the ECAS.

The comparison between Swedish, German and Polish healthy subjects revealed significant differences in performance in certain ECAS domains, not only for the total group, but also when stratified for age and education subgroups (Figure 1). This was rather unexpected in a comparison study of cohorts from seemingly similar European countries. Both for the younger subgroups and for the groups with less years of education, the Swedish cohort scored higher in memory than the German and the Polish cohorts. These differences did not show in older subgroups and those with more years of education, but the older Swedish subgroup showed better performance in executive functioning than the respective Polish subgroup. For the higher education subgroup, the Polish and German cohorts scored higher in language than the Swedish group. These diverse differences in cognitive performance between the three cohorts highlight not only the importance of age- and education-adjusted cutoffs in general, but further emphasize differences in neuropsychological performance of populations of different countries and cultures. Cross-cultural differences in cognitive processes like memory and attention have been reported between Western culture and East-Asian cultures (33,34). Also, in a combined analysis of large international data sets, significant differences in cognitive performance were found for senior populations of the same age groups in the United States, Northern, Continental and Southern Europe, China, India and Mexico, respectively (26). In line with this, we have previously reported significant differences in ECAS cognitive performance of healthy subjects in China and Germany, most notably the Chinese controls performed higher in spelling compared to the German control cohort (22,27). In addition, Chinese ALS patients performed poorer in executive subfunctions and better in the language subfunction of spelling compared to German ALS patients (22). Part of these significant differences in ECAS performance across populations presented here and in a past study (22) may be attributed to different language versions and cultural adaptations of the ECAS, but also to distinct linguistic and cultural background characterizing each population. Differences in cognitive performance may also stem from diverse educational systems, lifestyle, physical and occupational activities, experience of different economic conditions and mental health, among others (23–26). In a recent pan-European comparison of the data from the Survey on Health, Aging and Retirement in Europe (SHARE)(35) with neuropsychological testing of more than 22,000 senior citizens, the Scandinavian populations (including Sweden) showed better baseline performance in verbal fluency and memory than Western Europe (including Germany) and Central/Eastern Europe (including Poland), which were relatively on the same level (24). However, the Scandinavians had the highest rate of cognitive decline longitudinally (24), which is partly in line with our results regarding memory, where the younger Swedish group performed better than the respective German and Polish subgroups, while this difference was no longer apparent between older subgroups. However, this was not true for any other cognitive function of the ECAS, where the performance of older Swedes was equivalent or even better (in the case of executive functioning) compared to the older German and Polish subgroups. The Scandinavian populations in the SHARE-study had the largest proportion of highly educated, the smallest proportion of physically inactive and the lowest prevalence of cardiovascular diseases, all factors recognized to influence cognitive performance in the elderly (24). Overall, across the European regions significant differences in terms of sociodemographic and health characteristics have been observed (24), the exact mechanisms and the influence on overall cognition and its decline with age, however, are poorly understood and need further research. Hence, in order to make a statement about cognition in international ALS populations, it is important to adapt test instruments both linguistically and culturally for these populations and to standardize them for healthy samples. Comparisons between patient populations should then best be made by comparing z-scores to their respective healthy population, which is also important for international clinical studies.

This study presents novel general as well as age- and education-adjusted cutoffs for the adapted Swedish and Polish ECAS versions. Also for the first time, it shows statistically that seemingly similar healthy European cohorts perform differently in the respective ECAS. We may only speculate on reasons for these discrepancies, whether this is due to differences in the population itself or due to the linguistic and cultural adaptation of the ECAS. When interpreting the results, it should be noted that some subgroups have small sample sizes, which constrains generalizable conclusions. Also, it should be mentioned that the Swedish ECAS was only done in oral version, however, comparing the oral and written versions in the German and Polish ECAS showed no differences. The next step are validation studies for the Swedish and Polish ECAS. In addition, ECAS versions B and C are about to be standardized and validated for repeated measures, a step that greatly expands neuropsychological testing and prevents learning effects.

Conclusions and relevance

In summary, the study presents for the first time cutoffs for the Swedish and Polish ECAS and shows the importance of age- and education-adjusted ECAS cutoffs not only in general, but also for populations of different countries. The results have implications when comparing cognitive performance in studies across populations (e.g. when comparing patients with ALS or FTD with a C9orf72HRE mutation in different countries) but also when using ECAS as an instrument for inclusion assessment or outcome measure in international clinical drug trials.

Acknowledgements

We thank the many individuals who participated in this study. We thank Professor Thomas H. Bak from the University of Edinburgh for his help in translating the Polish version of ECAS. We also thank Dr. Lillian Carlsson Pähn from the Eksjö Community Hospital for participating in the validation of the Swedish version of ECAS in 2016.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data availability statement

Respecting the privacy of the participants and adhering to the European Union General Data Protection Regulation (EU) 2016/679 (GDPR), the data underlying the findings of this study are available from the authors (email). The national versions of ECAS used in this study are freely available for noncommercial use at the ECAS website.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This is an EU Joint Programme – Neurodegenerative Disease Research (JPND) project (“NEEDSinALS” 01ED1405). The project is supported through the following organizations under the egis of JPND—www.jpnd.eu e.g. Germany, Bundesministerium für Bildung und Forschung (BMBF, FKZ); Sweden, Vetenskapsrådet Sverige; Poland, Narodowe Centrum Badan’ i Rozwoju (NCBR). This work was additionally funded by Bundesministerium für Bildung und Forschung (FTLDc O1GI1007A, MND-Net 01GM1103A; PaCeMed 01DS18031), the Kompetenznetzwerk Präventivmedizin Baden-Württemberg (K.N.K.B.008.04), the Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), the Swedish Brain Foundation [grants no. 2013-0279, 2016-0303, 2018-0310], the Swedish Research Council [grants no. 2012-3167, 2017-03100], the Knut and Alice Wallenberg Foundation [grants no. 2012.0091, 2014.0305], the Västerbotten County Council [grant no. 2013-7590]. The funding sources played no role in the preparation of this manuscript.