Skip to main content

Quality of life and depression in patients with amyotrophic lateral sclerosis – does the country of origin matter?



Given the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients’ wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors.


314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain.


Patients from all three countries showed similar levels of functional impairment (ALSFRS-R). Overall, ALS patients assessed their quality of life as lower compared to HCs (p < 0.001 for the anamnestic comparative self-assessment (ACSA), p = 0.002 for the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW). Also, the German and Swedish patients, but not the Polish, reported higher depression levels than the corresponding HCs (p < 0.001). Analysis of ALS groups revealed that functional impairment was related to a lower quality of life (ACSA) and higher depression levels among German ALS patients. Longer time since diagnosis predicted lower depression and (in male subjects) higher quality of life.


ALS patients assess their quality of life and mood lower than healthy individuals within the studied countries. The relationships between clinical and demographic factors are moderated by country of provenance, which bears implications for the design and interpretation of scientific and clinical studies, which should reflect the complexity and heterogeneity of mechanisms determining QoL.

Peer Review reports


Amyotrophic lateral sclerosis is a progressive disease that involves degeneration of the central and peripheral motor system [28] leading finally to quadriplegia, anartria, aphagia and respiratory failure [20]. The course of the disorder is inauspicious with 50% of patients dying within three years of onset [28] but up to 10% surviving for over 10 yearswithout intervention [16, 20]. In the terminal stage, patients may develop locked-in syndrome (LIS) characterized by total loss of movements and communication with preserved consciousness [23]. Currently, approved neuroprotective interventions are limited to riluzole and edaravone, both with modest clinical effect [41, 50]. A combination of sodium phenylbutyrate and tauroursodeoxycholic acid (TUDCA) was recently approved in Canada based on data from the CENTAUR phase-2 study [18]. A phase 3 study PHOENIX of the above combination is presently on-going [43]. As the disease progresses, all patients face a number of difficult decisions to make [5], including for life-extending interventions like non-invasive or invasive ventilatory support, placement of a gastro-feeding tube to secure nutrition. A wide range of support equipment is frequently necessary to enable the patient to stay at home (and not move to a nursing facility) and preserve some degree of communication (e.g. eye tracking communication devices) even in patients with a very advanced disease [4]. A variety of drugs are frequently needed to reduce affective lability, anxiety, depression, nausea, dyspnea and/or pain [4]. For the lack of effective, disease-arresting interventions,the palliative care of the ALS patient and their relatives is symptomatic,with a focus on optimizing personal well-being. Its predictors analyzed to date include clinical state, comorbidities, pain, subjective quality of life, depression, demographic factors (sex, education, employment status), religion and spiritual needs [11, 27, 33, 38]. We here hypothesize that the country of provenance, with its cultural/religious characteristics and dominant value systems might co-determine the quality of life and depression levels in patients with ALS. Hence we prospectively assess the quality of life and depression in patients with ALS and matched healthy controls from threewidely different European countries (Poland, Germany, Sweden) and the relationship of these indices with socio-demographic and clinical factors. The three countries lay in a close geographic proximity in the Northern part of Europe but differed in historically-determined political situation and dominant socio-religious background (Sweden being liberal and historically protestant, Poland generally traditional and catholic and Germany, both).



Three hundred and fourteen ALS patients were consecutively recruited at university in- and out-patient clinics in Warsaw (n = 120), Ulm (n = 140) and Umea (n = 54) prior to the COVID-19 pandemics. They constituted approximately 60–80% of all consecutive patients consulted fulfilling the inclusion criteria at these centers. The most frequent reasons for not participating in the study were patients’ limited time for a visit due to a long commute, mental fatigue, advanced physical impairment and/or lack of informed consent.

The inclusion criteria were: age > 18 years, clinically definite, probable or probable laboratory-supported ALS according to the El Escorial revised criteria [9], sporadic or familial ALS, time since diagnosisof at least 3 months and Polish/German/Swedish mother tongue. Participants with major cognitive impairment and other neurological, psychiatric or general conditions that could (physically or psychologically) potentially influence the study outcome (e.g., diabetes mellitus, stroke or bipolar disease) were excluded from the sample. The healthy control group (HC) consisted of 311 age-, gender-, and education-matched individuals from the three respective countries (n = 100, n = 100 and n = 111) without the diagnosis of neurodegenerative or psychiatric condition. The patients werecompared for age, sex, education and functional status.

Data collection

The study procedures were performed by neurologists specialized in neuromuscular diseases and certified clinical psychologists. The questionnaires and interviews were conducted in patients’ native languages.

Clinical data

Functional/clinical status was assessed with the ALS Functional Rating Scale revised form (ALSFRS-R), with results ranging from 0 (locked-in state) to 48 (no functional impairment) [10]. The clinical assessment included the disease duration (time from first definite paretic disease symptom to the day of the survey), the time from diagnosis (time interval from the diagnosis of ALS to the day of the survey) in months, the possible use of a gastric feeding tube (percutaneous endoscopic gastrostomy - PEG or radiologically inserted gastrostomy RIG), invasive (IV) and non-invasive ventilation (NIV).

Quality of life and depression measures

The measure of global QoL was done with the anamnestic comparative self-assessment (ACSA), which allows estimating current overall well-being on a -5 to 5 scale with the extremes anchored at the memory of the worst (-5) and best (5) periods in the subject’s life [7, 8]. Subjective QoL measurement was obtained using the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW) [19, 30]. This tool first allows subjects to indicate the five most important areas of their lives. This step is followed by an assessment of the subjective importance and satisfaction related to each of the areas. The final numeric score of SEIQoL-DW is expressed on a 0 to 100 scale [19].

Finally, depressiveness was measured with the ALS-Depression-Inventory 12 Items (ADI-12). Numeric scores on that scale range from 12 to 48 with higher results indicating lower mood levels [17].

For the lack of validated Polish and Swedish translations and for the purpose of the study, all three tools were adapted from the original English versions. To ensure high levels of accuracy and content validity, in each language the same procedure was followed, including translation, independent back-translation, and final verification performed by experienced clinical psychologists fluent in English and the required target language. For the German versions, the existing previously validated translations were used.

Regarding the psychometric properties, neither ACSA (as a single-item measure) nor SEIQoL-DW (with its idiographic approach) allows for the assessment of internal consistency, however, both tools were extensively used in the studies of severely ill populations and have satisfactory psychometric properties, for more in-depth analyses: [44] and [7]. The reliability of ADI-12 was satisfactory in all three tested groups (Cronbach alpha = 0.80, 0.91 and 0.89 for Polish, Swedish and German participants, respectively).


The pain was expressed on a quantitative scale (frequency of occurrence pain: How often do you feel pain? 1 = never to 6 = every day; the intensity of pain: How severe is this pain? 1 = lack of pain to 6 = unbearable pain).

Statistical analysis

Continuous variables are reported as means and standard deviations and discrete variables as frequencies and percentages. Two-way ANOVA with bootstrapped p-values (2000 samples) and logistic regression were used to assess the effects of Country (Poland vs. Germany vs. Sweden) and ALS Diagnosis (ALS patients vs. healthy controls) in explaining group differences observed for continuous and dichotomous dependent variables. Main effects in ANOVA were interpreted using Tukey post-hoc tests and interactions by computing simple effects of Diagnosis within each country.

Comparisons of clinical characteristics across ALS groups were conducted using one-way ANOVA (with Tukey post-hocs) and Chi2 test (with Bonferroni-corrected post-hocs).

Additionally, the key quality of life indicators (ACSA, SEIQoL-DW) and depression (ADI) were tested using multivariate regression including all main effects and two-way interactions of predictors. To facilitate interpretation of the coefficients, categorical variables were contrast coded and continuous predictors – mean-centered prior to analysis. P-values < 0.05 were considered statistically significant. Computations were conducted using IBM SPSS (version 25) and R version 4.0.2 [35].

Power and sensitivity calculation

The study was a part of the JPND funded scientific project „NEEDS in ALS” [48] focusing on the end-of-life decisions of patients with ALS. Details of the initial power calculations specific to the primary goals of the project (not directly related to this publication) are available in [5].

Considering the aims and design of the study, we initially performed sensitivity analysis using G*POWER (ver. 3.1, [13]). These showed that - given available sample size and an alpha level of 0.05 - our design offered sufficient power to detect small to small-medium effects (as defined using conventional cut-offs, see: [12]). More specifically, 80% power in 2-way ANOVA was obtained for ηp2 = 0.01 (main effect of diagnosis) and ηp2 = 0.02 (main effect of country and country x diagnosis interaction), in 1-way ANOVA (ALS groups) for ηp2 = 0.03 effects, and, in the regression models, for f2 = 0.07 (tests of single predictors).


Demographic characteristics

No significant effects were observed in the distribution of gender across groups (see Table 1, which summarizes the demographic characteristics of ALS patients and control cohorts, for all the descriptive statistics). ALS patients were slightly older than controls (p = 0.021). Polish individuals were younger than Swedish and German subjects (p = 0.007) and reported a higher level of education compared to the Germans cohorts (p = 0.005). For the Swedish cohort, the control group had a higher level of education than the ALS patients groups (Country x Diagnosis interaction, p = 0.005).

Table 1 Descriptive statistics and between-group comparisons of the demographic and clinical characteristics

Clinical characteristics of the three ALS cohorts

There were significant differences between countries in the disease duration (p < 0.001) and time since diagnosis (p < 0.001). The highest means were observed in the Swedish cohort, followed by the Polish and German groups (detailed statistics are presented in Table 2, which summarizes the clinical characteristics of patients and controls). Despite varied disease duration, no significant differences in ALSFRS-R scores (p = 0.375) or progression rate (p = 0.098) at the time of evaluation were observed. Also, the proportion of patients with bulbar vs. spinal onset was similar across groups (p = 0.098).

Table 2 Comparison of clinical characteristics of German, Polish, and Swedish samples of ALS patients

Quality of life and depression measures

The two-way ANOVA revealed a similar pattern of results for all three key measures (effect of illness, effect of country and country x diagnosis interaction). The quality of life in ALS patients was lower (p < 0.001 for ACSA, p = 0.002 for SEIQoL-DW) and depression levels higher compared to control groups (p < 0.001, see Table 1; Fig. 1 for descriptive statistics). Significant effects of country were revealed for all measures (each p < 0.001) with the Swedish sample reporting higher quality of life and lower depression level than the two other groups, and Polish participants obtaining lower SEIQoL-DW and higher depression scores when compared with other countries. Noticeably, a significant country x diagnosis interaction was observed for ADI scores, with ALS groups scoring on average higher than controls in both Germany and Sweden, but not in Poland.

Fig. 1
figure 1

Mean scores of ACSA (a), SEIQoL-DW (b), and ADI (c) across studied groups. Error bars depict 95% bootstrap confidence intervals

Note: ACSA: anamnestic comparative self-assessment; SEIQoL-DW: Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting; ADI: ALS-Depression-Inventory 12 Items


Polish HCs assessed their severity of pain as higher compared to ALS patients (p = 0.020). There were no significant differences in severity and frequency of pain between patients and controls in the other groups. A significant effect of country was revealed for frequency of pain (p = 0.043) with Polish patients reporting higher frequency than German and Swedish patients. There was no significant difference in the severity of pain between countries.

Multiple regression models in the ALS cohorts

A series of multiple regression models were fitted for each of the key indicators (ACSA, SEIQoL-DW and depression). For each model, the same set of predictors was used: country, age (in years), months since disease onset (disease duration) and gender. The regression model included the main effects and all two-way interactions of the predictors listed above, hence obtained differences might be interpreted as adjusted for demographic and clinical variables (significance of the tested effects is reported in Table 3, complete set of estimates in Table 4).

Table 3 Summaries of the multiple regression models predicting ACSA, SEIQoL-DW and ADI scores in ALS groups. Significant effects are printed in bold
Table 4 Regression coefficients obtained in multiple regression models predicting ACSA, SEIQoL-DW and ADI results in ALS patients

Analysis of ACSA scores revealed a significant main effect of the functional state: higher scores of ALSFRS corresponded to a higher quality of life (b = 0.05, p = 0.025). This relationship was moderated by the effects of the Country (p = 0.004 for the interaction effect, Fig. 1A). Simple slopes analysis showed that the ALSFRS-R - ACSA relationship was significant only in the German patients (b = 0.14, p < 0.001), whereas in Poland (b = -0.01, p = 0.901) and Sweden (b = 0.01, p = 0.848) no such effect was observed. Furthermore, a marginally significant association between sex and disease duration was observed (p = 0.046, Fig. 1B). In female participants there were no significant changes in ACSA related to the disease duration (b = 0.00, p = 0.790), while in male patients a longer disease duration was related to higher subjective life quality (b = 0.041, p = 0.013).

The model focused on SEIQoL-DW revealed a significant effect of the Country (p = 0.001). Pairwise comparisons showed that Polish participants declared a significantly lower quality of life (M = 64.2) when compared both with German (M = 71.8, p = 0.004) and Swedish participants (M = 75.8, p = 0.004).

Analysis of ADI scores showed that lower ALSFRS-R scores (b = -0.20, p < 0.001) and shorter disease duration (b = -0.07, p = 0.004) were independently both related to higher level of depression. A significant effect of the country (p = 0.002) could be explained by lower depression scores observed in Swedish patients (M = 21.43) when compared with Polish (M = 25.17, p = 0.001) and German (M = 24.68, p = 0.022) participants. The last significant effect, the interaction of ALSFRS-R and the country (p = 0,026, Fig. 1C), closely mirrored effects observed for ACSA scores. ALSFRS-R was not significantly related to declared depression in Polish (b = − 0.09, p = 0.31) and Swedish (b = -0.16, p = 0.06) patients, while in German patients a lower ALSFRS-R score predicted a significantly higher depression levels (b = -0.36, p < 0.001). Due to a low number of patients using PEG or NIV/IV, these variables could not be included as predictors in the regression analyses. Partial correlations between PEG and NIV presence and quality of life measures controlling for the effects of sex, age, ALS-FRS results, and time since ALS onset showed no significant effects (all uncorrected p/values > 0.1; see Suppl. Material).


Subjective life satisfaction is conditioned by a combination of physical, psychological, social and environmental factors. The determinants of wellbeing in ALS exceed medical and physical domains. For a progressive and irreversible loss of physical autonomy along the disease course, social, intellectual and spiritual factors may have a more prominent role [11, 14, 40]. We hypothesized that, in this context, both socio-economical and socio-cultural factors differentiating studied countries might significantly shape patients’ wellbeing.

Comparisons of ALS patients and healthy controls

Not surprisingly, the ALS patients in all three countries (n = 314) assessed their quality of life as lower than healthy individuals. Similar effects have previously been reported among German ALS patients at with more advanced disease stage and a longer duration (n = 159) [21] but not in an other smaller study cohorts [22, 24]. Furthermore, despite apparent differences between countries, neither of the two analyses performed on QoL measures revealed any interaction effects, suggesting that the negative impact of ALS on QoL is comparable across studied populations. This pattern of intercountry differences is not specific to our results and closely matches the results observed in many large-scale studies performed on representative samples, including our previous report [5]. Relatively highest levels of wellbeing indices are regularly reported in Sweden, followed by the results from Germany, and lowest scores from Poland (see: results of the Third European Quality of Life Survey [1]).

The coherent picture of the effects of diagnosis and country being additive, becomes more complex when contrasted with the results observed for depression, where significant effects of ALS could be observed only in Sweden and Germany, but not in the Polish group. This surprising finding seems to be driven mainly by unusually high depression scores in the Polish control group. Similarly, the analysis of pain intensity showed a paradoxical effect of significantly higher pain levels in healthy Polish controls when compared with ALS patients. Both these effects might be to some extent interpreted as symptoms of a culturally specific phenomenon known as the Polish culture of complaining [45]. From a broader methodological perspective, it illustrates that - even within the same country, language, and culture - the invariance of scores might be difficult to achieve.

Predictors of QoL and depression in ALS patients

In the second step of the analysis, the use of multivariate regression allowed us to disentangle more universal relationships from country-specific effects and better understand the contribution of clinical and demographic predictors in explaining the QoL and depression levels. However, before discussing the detailed results, it is essential to emphasize that we describe a multivariate model adjusted for the differences in scores across countries. This strategy allows us to interpret the effects of other predictors more confidently without assuming full invariance of scores among countries/language versions.

We start the discussion by addressing one of the ongoing debates in ALS literature - the potential significance of functional state in explaining patients’ psychological wellbeing. The association between a higher quality of life and patients’ disease progression was reported in single- (n = 330) and multi-center (n = 325) studies conducted in Germany [34, 49], as well as Iranian (n = 132) and Brazilian (n = 45) cohorts [3, 39]. On the other hand, in an American study (n = 62) Robbins et al. showed that the QoL was not determined by physical decline in general [37]. Similar incoherence was observed in studies focused on depression levels. Poor physical state correlated with higher depression levels (as measured using Beck Depression Inventory) [21] in German patients. At the same time, no such correlations were observed in smaller samples from the US (n = 56 and n = 36, respectively) [32, 36] and Germany [24]. Our results contribute to that discussion by revealing a considerable heterogeneity of effects across countries. In our case, results from Poland and Sweden suggest no relationship between the functional state and depression or quality of life measured by ACSA, and results from Germany showing significant negative psychological consequences of ALS progression. To the best of our knowledge, no such results were ever reported within a single, large scale and multinational study.

Considering a broad range of predictors and their interactions, we could contribute to a discussion on a second contentious issue - the adaptation process following ALS diagnosis. That is also an area of research far from reaching a consensus. Earlier American [6] and German [21] studies carried out in patients at a similar or more advanced disease stage did not detect any correlations between the disease duration and depression levels. However, prospective studies have revealed that ALS patients’ desire to hasten death decreased significantly within a year of diagnosis, despite progressive physical function decline [25]. It supports the existence of one or more efficient adaptation mechanism. In our analysis of depression levels, a longer disease duration was predictive of a relatively better mood (after controlling for all the covariates). These results are coherent with more recent studies [22, 26]. At the same time, a similar adaptive mechanism was observed in our analysis of the subjective QoL, but the disease length’s effect was this time limited to male patients only. This findings again points to the vital role of moderators and the complexity of the studied phenomena.

Finally, as our study was conducted simultaneously in three large cohorts, it might also be worth mentioning one of the negative results of the statistical analyses, namely the lack of statistically significant effects of age. Age is recognized to influence the QoL and depression measures in the general population [2, 42]. In ALS, it was shown to be related to specific coping strategies [31] and likely to influence processes of decision-making related to care [15]. In the specific context of ALS, the wellbeing mainly depended on efficient individual coping strategies and velocity of disease progression [24], rather than processes significantly determined by age (or its correlates), as shown in our cohort.

To summarize, we believe that our study provides a cautionary tale by showing the intrinsic complexity and heterogeneity of the mechanism determining patients’ psychological wellbeing. The set of factors determining QoL or depression levels seems to significantly vary between countries, which should be taken into account both in the interpretation of the existing literature, as well as in designing future research (including international clinical trials in ALS, where the changes in QoL and depression following the pharmacological intervention are frequently secondary end-points) [46, 47, 29 and others].

Study limitations

1) The patients who participated in the study were followed at specialized multidisciplinary care centers, which might have influenced their overall well-being.

2) Some of the Swedish patients who were recruited to the study had a longer disease duration and comparable functional impairment implicating a more benign disease course and longer adaptation period.

3) The regression approach adjusted for the non-equality of mean scores between ALS groups. However, the interpretability of the regression coefficients of main effects still required metric invariance. Strong violations of that assumption could cast doubt on some of our conclusions.

4) The analysis would be more comprehensive if it considered the socioeconomic background and information about support (e.g. health-system, social support, etc.). Regrettably, such data were not available within this project.

5) The data was gathered prior to the COVID19 pandemic and does not reflect the present (unstable) situation of the healthcare systems in the three countries. At the same time, our results may reflect more stable processes not affected by transient external factors.


Our results confirmed that ALS patients assess their quality of life as lower and depression levels as higher than healthy individuals. We also demonstrate that both QoL and depression (at least in some studied subgroups of patients) are significantly affected by two opposing forces: the beneficial process of adaptation to the diagnosis, and declining functional state leading to significant psychological costs. Our results also bear methodological implications, pointing to the importance of the use of country-specific control groups, taking into account the heterogeneity of the effects and limited generalizability of the results across cultural contexts (even in relative geographical proximity) at all stages of the research process.

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.



Amyotrophic lateral sclerosis, HCs:healthy controls


Quality of life


Amyotrophic lateral sclerosis functional rating scale-revised


Anamnestic comparative self-assessment


Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting


Locked-in syndrome


Sodium phenylbutyrate and tauroursodeoxycholic acid


Percutaneous endoscopic gastrostomy


Radiologically inserted gastrostomy


Invasive ventilation


Non-invasive ventilation


ALS-Depression-Inventory 12 Items


  1. Ahrendt D, Dubois H, Mezger E. (2015). An overview of quality of life in Europe. Global handbook of quality of life, 625–661.

  2. Alcañiz M, Solé-Auró A. Feeling good in old age: factors explaining health-related quality of life. Health Qual Life Outcomes Mar. 2018;13(1):48.

    Article  Google Scholar 

  3. Alencar MA, da Silva IMM, Hilário SM, de Andrade Rangel MF, Abdo JS, Araújo CM, Souza LC. Quality of life, disability, and clinical variables in amyotrophic lateral sclerosis. Arq Neuropsiquiatr. 2022;80(3):255–61.

    Article  PubMed  Google Scholar 

  4. Andersen PM, Abrahams S, Borasio GD, Carvalho M, Chio A, Van Damme P, Hardiman O, Kollewe K, Morrison KE, Petri S, Pradat PF, Silani V, Tomik B, Wasner M, Weber M. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force. Eur J Neurol. 2012;19(3):360–75.

    Article  PubMed  Google Scholar 

  5. Andersen PM, Kuźma-Kozakiewicz M, Keller J, Aho-Oezhan HEA, Ciecwierska K, et al. Therapeutic decisions in ALS patients: cross-cultural differences and clinical implications. J Neurol. 2018;265(7):1600–6.

    Article  PubMed  Google Scholar 

  6. Atassi N, Cook A, Pineda CM, Yerramilli-Rao P, Pulley D, Cudkowicz M. Depression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2011;12(2):109–12.

    Article  PubMed  Google Scholar 

  7. Bernheim JL. How to get serious answers to the serious question:‘How have you been?’: subjective quality of life (QOL) as an individual experiential emergent construct. Bioethics. 1999;13(3–4):272–87.

    Article  PubMed  Google Scholar 

  8. Bernheim JL, Theuns P, Mazaheri M, et al. The potential of Anamnestic Comparative Self-Assessment (ACSA) to Reduce Bias in the measurement of Subjective Well-Being. J Happiness Stud. 2006;7:227–50.

    Article  Google Scholar 

  9. Brooks BR, Miller RG, Swash M, Munsat TL. World Federation of Neurology Research Group on Motor Neuron Diseases: El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1(5):293–9.

    Article  CAS  PubMed  Google Scholar 

  10. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function, BDNF ALS Study Group (Phase III). J Neurol Sci. 1999;169(1–2):13–21.

    Article  CAS  PubMed  Google Scholar 

  11. Chio A, Gauthier A, Montuschi A, Calvo A, Di Vito N, Ghiglione P, Mutanii R. A cross sectional study on determinants of quality of life in ALS. J Neurol Neurosurg Psychiatry. 2004;75:1597–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cohen J. (1988). Statistical Power Analysis for the Social Sciences (2nd. Edition). Hillsdale, New Jersey, Lawrence Erlbaum Associates.

  13. Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41:1149–60.

    Article  PubMed  Google Scholar 

  14. Felgoise SH, Stewart JL, Bremer BA, Walsh SM, Bromberg MB, Simmons Z. The SEIQoL-DW for assessing quality of life in ALS: strengths and limitations. Amyotroph Lateral Scler. 2009;10:456–62.

    Article  PubMed  Google Scholar 

  15. Foley G, Timonen V, Hardiman O. Acceptance and decision making in amyotrophic lateral sclerosis from a life-course perspective. Qual Health Res. 2014;24(1):67–77.

    Article  PubMed  Google Scholar 

  16. Forsgren L, Almay BG, Holmgren G, Wall S, Acta Neurol, Scand, Forsgren L, Almay BG, Holmgren G, Wall S. (1983). Epidemiology of motor neuron disease in northern Sweden. Acta Neurol Scand, 68(1):20 – 9.

  17. Hammer EM, Häcker S, Hautzinger M, Meyer TD, Kübler A. Validity of the ALS-Depression-inventory (ADI-12)--a new screening instrument for depressive disorders in patients with amyotrophic lateral sclerosis. J Affect Disord. 2008;109(1–2):213–9.

    Article  PubMed  Google Scholar 

  18. Heo Y-A. (2022). Sodium Phenylbutyrate and Ursodoxicoltaurine: first approval, CNS drugs, Jul 30.

  19. Hickey AM, Bury G, O’Boyle CA, Bradley F, O’Kelly FD, Shannon W. A new short form individual quality of life measure (SEIQoL-DW): application in a cohort of individuals with HIV/AIDS. The BMJ. 1996;313(7048):29–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, Burrell JR, Zoin MC. Amyotrophic lateral sclerosis. Lancet. 2011;377:942–55.

    Article  CAS  PubMed  Google Scholar 

  21. Körner S, Kollewe K, Abdulla S, Zapf A, Dengler R, Petri S. Interaction of physical function, quality of life and depression in Amyotrophic lateral sclerosis: characterization of a large patient cohort. BMC Neurol. 2015. 15;84.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lulé D, Häcker S, Ludolph A, Birbaumer N, Kübler A. Depression and quality of life in patients with amyotrophic lateral sclerosis. Dtsch Arztebl Int. 2008;105(23):397–403.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lulé D, Zickler C, Häcker S, Bruno MA, Demertzi A, Pellas F, Laureys S, Kübler A. Life can be worth living in Locked-In syndrome. Prog Brain Res. 2009;177:339–51.

    Article  PubMed  Google Scholar 

  24. Lulé D, Ehlich B, Lang D, Sorg S, Heimrath J, Kübler A, Birbaumer N, Ludolph AC. Quality of life in fatal disease: the flawed judgement of the social environment. J Neurol. 2013;260(11):2836–43.

    Article  PubMed  Google Scholar 

  25. Lulé D, Nonnenmacher S, Sorg S, Heimrath J, Hautzinger M, Meyer T, Kübler A, Birbaumer N, Ludolph AC. Live and let die: existential decision processes in a fatal disease. J Neurol. 2014;261(3):518–25.

    Article  PubMed  Google Scholar 

  26. Lulé D, Kübler A, Ludolph AC. Ethical principles in patient-centered Medical Care to support quality of life in amyotrophic lateral sclerosis. Front Neurol. 2019;10:259.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Medrano CRV, Aho-Özhan H, Weiland U, Uttner I, Ludolph AC, Lulé D. Disease progression but not physical state per se determines mental wellbeing in ALS. J Neurol. 2020;267:3593–601.

    Article  Google Scholar 

  28. Mitchell JD, Borasio GD. Amyotrophic lateral sclerosis. Lancet. 2007;369:2031–41.

    Article  CAS  PubMed  Google Scholar 

  29. Mora JS, Genge A, Chio A, Estol CJ, Chaverri D, Hernández M, Marín S, Mascias J, Rodriguez GE, Povedano M, Paipa A, Dominguez R, Gamez J, Salvado M, Lunetta C, Ballario C, Riva N, Mandrioli J, Moussy A, Kinet JP, Auclair C, Dubreuil P, Arnold V, Mansfield CD, Hermine O. AB10015 STUDY GROUP, Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2020;21(1–2):5–14.

    Article  CAS  PubMed  Google Scholar 

  30. Neudert C, Wasner M, Borasio GD. Patients’ assessment of quality of life instruments: a randomised study of SIP, SF-36 and SEIQoL-DW in patients with amyotrophic lateral sclerosis. J Neurol Sci. 2001;191(1–2):103–9.

    Article  CAS  PubMed  Google Scholar 

  31. Oh J, An J, Park K. Coping in people with amyotrophic lateral sclerosis and motor neuron disease: systematic review. J Clin Nurs. 2021;30(13–14):1838–53.

    Article  PubMed  Google Scholar 

  32. Yerramilli-Rao P, Cudkowicz M, Atassi N. Functional decline is Associated with hopelessness in amyotrophic lateral sclerosis. J Neurol Neuropsychol. 2017;8(2). Sherman A .Atassi H.

  33. Pagnini F, Banfi LCh, Rossi P, Fossati G, Marconi F, Castelnuovo A, Corbo G, Molinari M E. Pain in Amyotrophic lateral sclerosis: a psychological perspective. Neurol Sci. 2012;33:1193–6.

    Article  PubMed  Google Scholar 

  34. Peseschkian T, Cordts I, Günther R, Stolte B, et al. A Nation-Wide, multi-center study on the quality of life of ALS Patients in Germany. Brain Sci. 2021;14(3):372.

    Article  Google Scholar 

  35. R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2020.

    Google Scholar 

  36. Rabkin JG, Wagner GJ, Del Bene M. Resilience and distress among amyotrophic lateral sclerosis patients and caregivers. Psychosom Med. 2000;62:271–9.

    Article  CAS  PubMed  Google Scholar 

  37. Robbins RA, Simmons Z, Bremer BA, Walsh SM, Fischer S. Quality of life in ALS is maintained as physical function declines. Neurology. 2001;56:442–4.

    Article  CAS  PubMed  Google Scholar 

  38. Schrempf T, Finsel J, Uttner I, Ludolph AC, Lulé D. Neuropsychological deficits have only limited impact on psychological well-being in amyotrophic lateral sclerosis. J Neurol. 2022;269:1369–74.

    Article  PubMed  Google Scholar 

  39. Shamshiri H, Fatehi F, Abolfazli R, Harirchian MH, Sedighi B, Zamani B, Roudbari A, Razazian N, Khamseha F, Nafiss S. Trends of quality of life changes in amyotrophic lateral sclerosis patients. J Neurol Sci. 2016;368:35–40.

    Article  PubMed  Google Scholar 

  40. Simmons Z, Bremer BA, Robbins RA, Walsh SM, Fischer S. Quality of life in ALS depends on factors other than strength and physical function. Neurology. 2000;55:388–92.

    Article  CAS  PubMed  Google Scholar 

  41. Sojka P, Andersen PM, Forsgren L. Effects of riluzole on symptom progression in amyotrophic lateral sclerosis. Lancet. 1997;349(9046):176–7.

    Article  CAS  PubMed  Google Scholar 

  42. Stordal E, Mykletun A, Dahl AA. The association between age and depression in the general population: a multivariate examination. Acta Psychiatr Scand. 2003;107(2):132–41.

    Article  CAS  PubMed  Google Scholar 

  43. Sun Y, Bedlack R, Armon C, Beauchamp M, Bertorini T, Bowser R, Bromberg M, Caress J, Carter G, Crayle J, Cudkowicz ME, Glass JD, Jackson C, Lund I, Martin S, Paganoni S, Pattee G, Ratner R, Salmon K, Wicks P. ALSUntangled #64: butyrates. Amyotroph Lateral Scler Frontotemporal Degener. 2022;28:1–6. &cond=ALS&draw=2&rank=4), NCT05021536.

    Article  CAS  Google Scholar 

  44. Wettergren L, Kettis-Lindblad A, Sprangers M, Ring L. The use, feasibility and psychometric properties of an individualised quality-of-life instrument: a systematic review of the SEIQoL-DW. Qual Life Res Aug. 2009;18(6):737–46.

    Article  CAS  Google Scholar 

  45. Wojciszke B. The negative social world: the polish culture of complaining. Int J Sociol. 2004;34(4):38–59.

    Article  Google Scholar 

  46. WRITING GROUP ON BEHALF OF THE EDARAVONE (MCI-186) ALS 17 STUDY GROUP. Exploratory double-blind, parallel-group, placebo-controlled extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(sup1):20–31.

    Article  CAS  Google Scholar 

  47. WRITING GROUP ON BEHALF OF THE EDARAVONE (MCI-186) ALS 18 STUDY GROUP. Exploratory double-blind, parallel-group, placebo-controlled study of edaravone (MCI-186) in amyotrophic lateral sclerosis (Japan ALS severity classification: Grade 3, requiring assistance for eating, excretion or ambulation). Amyotroph Lateral Scler Frontotemporal Degener. 2017;18(sup1):40–8.

    Article  CAS  Google Scholar 


  49. Vázquez MC, Aho-Özhan H, Weiland U, Uttner I, Ludolph AC, Lulé D. Disease progression but not physical state per se determines mental wellbeing in ALS. J Neurol. 2020;267(12):3593–601.

    Article  Google Scholar 

  50. Yoshino H. Edaravone for the treatment of amyotrophic lateral sclerosis. Expert Rev Neurother. 2019;19(3):185–93.

    Article  CAS  PubMed  Google Scholar 

Download references


The authors gratefully acknowledge the ALS patients and their families who made this study possible.


This is an EU Joint Program – Neurodegenerative Disease Research (JPND; 01ED1405) project. The project is supported through the following organizations under the aegis of JPND –, e.g. Germany, Bundesministerium für Bildung und Forschung (BMBF, FKZ), Sweden, Vetenskapsr å det Sverige, and Poland, Narodowe Centrum Badan i Rozwoju (NCBR). This work was additionally supported by the Deutsche Forschungsgemeinschaft (LU 336/13 − 2 BI 195/54 − 2), the BMBF (#01GM1103A) ,the Knut and Alice Wallenberg Foundation (KAW #2014.0305), the Kompetenznetzwerk Baden-Württemberg and ERA-NET-E Rare 3/IV/MAXOMOD/11.2020. The funding bodies played no role in the design of the study and collection, analysis, interpretation of data, and in writing the manuscript.

Author information

Authors and Affiliations



KC: the design of the substudy on wellbeing, acquisition of data, analysis and interpretation of data, writing the first draft and drafting the article, DL: conception and study design, revision, final approval, MB: analysis and interpretation of data, OH: carried out the data collection, German database preparation, draft review, AM?: carried out the data collection, contribution to the Polish database, draft review, JF: carried out the data collection, German database preparation, draft review, KN: carried out the data collection, contribution to the Polish database, review and editing, PMA: Swedish database preparation, revision, final approval, ACL: revision, final approval, MKK: conception and study design, analysis and interpretation of data, revision, final approval. All the authors have read and agreed to the final manuscript.

Corresponding author

Correspondence to Magdalena Kuźma-Kozakiewicz.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the relevant national ethical committees: the Bioethics committee of the Medical University of Warsaw, Poland (KB/138/2013), Ethikkommission Universität Ulm, Germany (Nr. 19/12 MND-Net) and Etikprövningsnämnden, EPN, Sweden (Dnr 2013-64-31 M, Dnr 2017-200-32 M and Dnr 2017-441-32 M) in accordance with theprinciples of the 1964 Declaration of Helsinki and its later amendments. All participants signed an informed consent from according to the GCP prior to inclusion.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ciećwierska, K., Lulé, D., Bielecki, M. et al. Quality of life and depression in patients with amyotrophic lateral sclerosis – does the country of origin matter?. BMC Palliat Care 22, 72 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: