Skip to main content
SpringerLink
Log in

Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with loss of muscle function. The pathogenesis is still unclear and the heterogeneity of ALS phenotypes is huge. We investigated a large population of ALS patients and controls concerning comorbidities and medications to detect specific risk or protective factors regarding onset and progression of ALS.

Methods

We investigated a cohort of 200 ALS patients pro- and retrospectively compared to a control group. For comparison of frequencies of comorbidities and medication intake, uni- and multivariate binary logistic regressions were performed. To analyze the influence of comorbidities and medication on the progression of ALS, we used linear regression analysis.

Results

ALS patients showed a relevantly higher prevalence of strokes and depression compared to controls. Moreover, ALS patients reported relevantly more often regular physical activity and their BMI was lower. The coexistence of coronary heart disease was associated with a relevantly faster disease progression. Intake of contraceptives was relevantly higher in controls compared with ALS patients.

Conclusions

Our results suggest stroke, lower BMI, and regular physical activity as risk factors for ALS. Strokes could be a possible trigger of the pathogenetic pathway of ALS and the lower BMI with consecutively lower rate of hyperlipidemia supports the hypothesis of premorbid hypermetabolism in ALS patients. Coexistence of coronary heart disease possibly has a negative influence on respiratory involvement. Contraceptives could be beneficial due to a protective effect of estrogen. Information on influencing factors can help to elucidate the pathogenesis of ALS or provide approaches for possible therapeutic options.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Silani V, Ludolph A, Fornai F (2017) The emerging picture of ALS: A multisystem, not only a “motor neuron disease”. Arch Ital Biol 155:99–109

    PubMed  Google Scholar 

  2. Gallo V, Wark PA, Jenab M et al (2013) Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort. Neurology 80:829–838

    Article  Google Scholar 

  3. O’Reilly ÉJ, Wang H, Weisskopf MG et al (2013) Premorbid body mass index and risk of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 14:205–211. https://www.ncbi.nlm.nih.gov/pubmed/23134505

  4. Dorst J, Kühnlein P, Hendrich C, Kassubek J, Sperfeld AD (2011) Ludolph AC (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258:613–617

    Article  CAS  Google Scholar 

  5. Dupuis L, Corcia P, Fergani A et al (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis symbol. Neurology 70(13):1004–1009

    Article  CAS  Google Scholar 

  6. Körner S, Kollewe K, Ilsemann J et al (2013) (2013) Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis. Eur J Neurol 20:647–654

    Article  Google Scholar 

  7. Moglia C, Calvo A, Canosa A et al (2017) Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study. Amyotroph Lateral Scler Front Degener 18:590–597

    Article  Google Scholar 

  8. Turner MR, Wotton C, Talbot K, Goldacre MJ (2012) Cardiovascular fitness as a risk factor for amyotrophic lateral sclerosis: Indirect evidence from record linkage study. J Neurol Neurosurg Psychiatry 83:395–398

    Article  Google Scholar 

  9. Harwood CA, Westgate K, Gunstone S et al (2016) Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis? Amyotroph Lateral Scler Front Degener 17:377–384

    Article  Google Scholar 

  10. Longstreth WT, McGuire V, Koepsell TD, Wang Y, van Belle G (1998) Risk of amyotrophic lateral sclerosis and history of physical activity: a population-based case-control study. Arch Neurol 55:201–206. https://www.ncbi.nlm.nih.gov/pubmed/9482362

  11. Patel BP, Hamadeh MJ (2009) Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis. Clin. Nutr 28:604–617

    Article  CAS  Google Scholar 

  12. Carreras I, Yuruker S, Aytan N et al (2010) Moderate exercise delays the motor performance decline in a transgenic model of ALS. Brain Res 1313:192–201

    Article  CAS  Google Scholar 

  13. Prell T, Gaur N, Stubendorff B, Rödiger A, Witte OW, Grosskreutz J (2019) Disease progression impacts health-related quality of life in amyotrophic lateral sclerosis. J Neurol Sci 397:92–95. https://www.ncbi.nlm.nih.gov/pubmed/30597420

  14. Korner S, Kammeyer J, Zapf A et al (2019) Influence of environment and lifestyle on incidence and progress of amyotrophic lateral sclerosis in A German ALS population. Aging Dis Int Soc Aging Dis 10:205–216

    Google Scholar 

  15. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169(1–2):3–21

  16. Hollinger SK, Okosun IS, Mitchell CS (2016) Antecedent disease and amyotrophic lateral sclerosis: What is protecting whom? Front Neurol 7:47

    Article  Google Scholar 

  17. Beghi E, Logroscino G, Chiò A et al (2010) Amyotrophic lateral sclerosis, physical exercise, trauma and sports: results of a population-based pilot case-control study. Amyotroph Lateral Scler 11:289–292

    Article  Google Scholar 

  18. Pupillo E, Messina P, Giussani G et al (2014) Physical activity and amyotrophic lateral sclerosis: a European population-based case-control study. Ann Neurol 75:708–716. https://www.ncbi.nlm.nih.gov/pubmed/24706338.

  19. Abel EL (2007) Football increases the risk for Lou Gehrig’s disease, amyotrophic lateral sclerosis. Percept Mot Skills 104:1251–1254

    Article  Google Scholar 

  20. Chiò A, Benzi G, Dossena M, Mutani R, Mora G (2005) Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players. Brain 128:472–476

    Article  Google Scholar 

  21. Huisman MHB, Seelen M, De Jong SW et al (2013) Lifetime physical activity and the risk of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 84:976–981

    Article  Google Scholar 

  22. Mattsson P, Lönnstedt I, Nygren I, Askmark H (2012) Physical fitness, but not muscle strength, is a risk factor for death in amyotrophic lateral sclerosis at an early age. J Neurol Neurosurg Psychiatry 83:390–394

    Article  Google Scholar 

  23. Seelen M, van Doormaal PTC, Visser AE et al (2014) Prior medical conditions and the risk of amyotrophic lateral sclerosis. J Neurol 261:1949–1956

    Article  CAS  Google Scholar 

  24. Sutedja NA, Van Der Schouw YT, Fischer K et al (2011) Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 82:638–642

    Article  CAS  Google Scholar 

  25. Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P (1999) Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53:1059–1063

    Article  CAS  Google Scholar 

  26. Jawaid A, Murthy SB, Wilson AM et al (2010) A decrease in body mass index is associated with faster progression of motor symptoms and shorter survival in ALS. Amyotroph Lateral Scler 11:542–548. https://www.ncbi.nlm.nih.gov/pubmed/20500116

  27. Dupuis L, Oudart H, René F, Gonzalez De Aguilar JL, Loeffler JP (2004) Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci USA 101:11159–11164

    Article  CAS  Google Scholar 

  28. Dardiotis E, Siokas V, Sokratous M et al (2018) Body mass index and survival from amyotrophic lateral sclerosis. Neurol Clin Pract 8:437–444

    Article  Google Scholar 

  29. Moura MC, Novaes MRCG, Eduardo EJ, Zago YSSP, Freitas RDNB, Casulari LA (2015) Prognostic factors in amyotrophic lateral sclerosis: a population-based study. PLoS One 10:e0141500. https://www.ncbi.nlm.nih.gov/pubmed/26517122

  30. Dedic SIK, Stevic Z, Dedic V, Stojanovic VR, Milicev M, Lavrnic D (2012) Is hyperlipidemia correlated with longer survival in patients with amyotrophic lateral sclerosis? Neurol Res 34:576–580

    Article  Google Scholar 

  31. Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10:75–82

    Article  CAS  Google Scholar 

  32. Bouteloup C, Desport J-C, Clavelou P et al (2009) Hypermetabolism in ALS patients: an early and persistent phenomenon. J Neurol 256:1236–1242. https://www.ncbi.nlm.nih.gov/pubmed/19306035

  33. Haverkamp LJ, Appel V, Appel SH (1995) Natural history of amyotrophic lateral sclerosis in a database population. Brain 118:707–719. https://brain.oxfordjournals.org/content/brain/118/3/707.full.pdf

  34. Turner MR, Goldacre R, Talbot K, Goldacre MJ (2016) Cerebrovascular injury as a risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 87:244–246

    Article  Google Scholar 

  35. Rosenbohm A, Kassubek J, Weydt P et al (2014) Can lesions to the motor cortex induce amyotrophic lateral sclerosis? J Neurol 261:283–290

    Article  Google Scholar 

  36. Sivandzade F, Bhalerao A, Cucullo L (2019) Cerebrovascular and Neurological Disorders: Protective Role of NRF2. Int J Mol Sci 20:3433

    Article  CAS  Google Scholar 

  37. Kahl A, Blanco I, Jackman K et al (2018) Cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases. Sci Rep 8:2701. https://www.ncbi.nlm.nih.gov/pubmed/29426953

  38. Mandrioli J, Ferri L, Fasano A et al (2018) Cardiovascular diseases may play a negative role in the prognosis of amyotrophic lateral sclerosis. Eur J Neurol 25:861–868

    Article  CAS  Google Scholar 

  39. D’Amico E, Factir-Litvak P, Santella RM, Mitsumoto H (2013) Clinical perspective of oxidative stress in sporadic ALS. Free Radic Biol Med 29:997–1003

    Google Scholar 

  40. Roos E, Mariosa D, Ingre C et al (2016) Depression in amyotrophic lateral sclerosis. Neurology 86:2271–2277

    Article  CAS  Google Scholar 

  41. Körner S, Kollewe K, Abdulla S, Zapf A, Dengler R, Petri S (2015) Interaction of physical function, quality of life and depression in amyotrophic lateral sclerosis: Characterization of a large patient cohort. BMC Neurol 2015:15

    Google Scholar 

  42. Lulé D, Häcker S, Ludolph A, Birbaumer N, Kübler A (2008) Depression and quality of life in patients with amyotrophic lateral sclerosis. Dtsch Arztebl Int 105:397–403. https://www.ncbi.nlm.nih.gov/pubmed/19626161

  43. Rabkin JG, Albert SM, Del Bene ML et al (2005) Prevalence of depressive disorders and change over time in late-stage ALS. Neurology 65:62–67

    Article  CAS  Google Scholar 

  44. Moore MJ, Moore PB, Shaw PJ (1998) Mood disturbances in motor neurone disease. J Neurol Sci 160(Suppl 1):S53–S56. https://www.ncbi.nlm.nih.gov/pubmed/9851650

  45. Verschueren A, Kianimehr G, Belingher C et al (2019) Wish to die and reasons for living among patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Front Degener 20:68–73

    Article  Google Scholar 

  46. Paganoni S, McDonnell E, Schoenfeld D et al (2017) Functional decline is associated with hopelessness in amyotrophic lateral sclerosis (ALS). J Neurol Neurophysiol. https://doi.org/10.4172/2155-9562.1000423

    Article  PubMed  PubMed Central  Google Scholar 

  47. Il CC, Lee YD, Gwag BJ, Cho SI, Kim SS, Suh-Kim H (2008) Effects of estrogen on lifespan and motor functions in female hSOD1 G93A transgenic mice. J Neurol Sci 268:40–47

    Article  Google Scholar 

  48. Groeneveld GJ, Van Muiswinkel FL, Sturkenboom JM, Wokke JHJ, Bär PR, Van Den Berg LH (2004) Ovariectomy and 17β-estradiol modulate disease progression of a mouse model of ALS. Brain Res 1021:128–131

    Article  CAS  Google Scholar 

  49. Heitzer M, Kaiser S, Kanagaratnam M et al (2017) Administration of 17β-estradiol improves motoneuron survival and down-regulates inflammasome activation in male SOD1(G93A) ALS mice. Mol Neurobiol 54:8429–8443. https://www.ncbi.nlm.nih.gov/pubmed/27957680

  50. Veldink JH, Sommer H, Weber M et al (2018) Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model. Lancet Neurol 17:423–433

    Article  Google Scholar 

  51. Mandrioli J, Malerba SA, Beghi E et al (2018) Riluzole and other prognostic factors in ALS: a population-based registry study in Italy. J Neurol 265:817–827

    Article  CAS  Google Scholar 

  52. Zoccolella S, Beghi E, Palagano G et al (2008) Analysis of survival and prognostic factors in amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 79:33–37

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The study was funded by the EU (ONWebDUALS project, JNPD 01ED1511B). We thank all project members and contributors.

Author information

Authors and Affiliations

  1. Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, C, Germany

    Kristin Diekmann, Alma Osmanovic, Olivia Schreiber-Katz, Susanne Petri & Sonja Körner

  2. Department of Neurology, Medical University of Warsaw, Warsaw, Poland

    Magdalena Kuzma-Kozakiewicz

  3. Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland

    Maria Piotrkiewicz

  4. Faculty of Medicine, Institute of Physiology-Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal

    Marta Gromicho & Mamede de Carvalho

  5. Department of Neurology, University Hospital Jena, Jena, Germany

    Julian Grosskreutz

  6. Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden

    Peter M. Andersen

  7. Department of Neurology, Faculty of Medicine, Akdeniz University, Antalya, Turkey

    Hilmi Uysal

  8. Center for Systems Neuroscience (ZSN), Hannover, Germany

    Susanne Petri

Authors
  1. Kristin Diekmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Magdalena Kuzma-Kozakiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Piotrkiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marta Gromicho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julian Grosskreutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter M. Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mamede de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hilmi Uysal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alma Osmanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Olivia Schreiber-Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Susanne Petri
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sonja Körner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sonja Körner.

Ethics declarations

Conflicts of interest

All authors declare that they do not have any conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 14 kb)

Supplementary file2 (DOC 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diekmann, K., Kuzma-Kozakiewicz, M., Piotrkiewicz, M. et al. Impact of comorbidities and co-medication on disease onset and progression in a large German ALS patient group. J Neurol 267, 2130–2141 (2020). https://doi.org/10.1007/s00415-020-09799-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-09799-z

Keywords

Search

Navigation