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

Diekmann, Kristin; Kuźma‐Kozakiewicz, Magdalena; Piotrkiewicz, Maria; Gromicho, Marta; Großkreutz, Julian; Andersen, Peter M.; Carvalho, Mamede de; Uysal, Hilmi; Osmanovic, Alma; Schreiber‐Katz, Olivia; Petri, Susanne; Körner, Sonja

doi:10.1007/s00415-020-09799-z

Cited by 33 publications

(45 citation statements)

References 47 publications

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“…Our unbiased approach identified a class dominated by cardiovascular disease and heart failure, which was associated with a modestly reduced survival in the initial analysis, replicating previous findings [1,3]. However, as cardiovascular disease is a composite endpoint of numerous pathophysiological processes that are individually strongly associated with age, it is possible that this grouping and modest survival effect was a reflection of the complex relationship with age and individual components for cardiovascular disease.…”

Section: Discussionsupporting

confidence: 79%

“…Furthermore, it is possible that particular patterns or clusters of comorbidities exist that interact with one another and MND to determine survival, hereafter termed multimorbidity patterns. For example, concomitant lung disease and heart failure may worsen MND‐related respiratory failure, and cardiovascular disease is associated with mortality, as suggested by previous literature [1,3].…”

Section: Introductionmentioning

confidence: 79%

“…A proportion of people with MND (pwMND) have comorbid disease [1][2][3][4][5][6], which could contribute to differential survival. If so, understanding this may allow for better personalised prognostic estimates, a more holistic approach to care, and refinement of pragmatic analyses of real-world disease cohorts and inclusive clinical trials.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of multimorbidity and its impact on survival in people with motor neuron disease

Glasmacher

Kearns

Larraz

et al. 2021

Euro J of Neurology

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

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Prevalence of multimorbidity and its impact on survival in people with motor neuron disease

Glasmacher

Kearns

Larraz

et al. 2021

Euro J of Neurology

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“…A study from Italy found that the presence of hypertension and heart disease such as heart failure or atrial fibrillation had a negative prognostic impact [129]. Another cohort study found that patients with coronary artery disease had faster progression [130]. This field of research needs further attention to clarify these issues and to search for other diseases that could impact on the progression of ALS.…”

Section: Concurrent Illnesses and Concurrent Medicationsmentioning

confidence: 99%

What do we know about the variability in survival of patients with amyotrophic lateral sclerosis?

McCombe

Garton

Katz

et al. 2020

Expert Review of Neurotherapeutics

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Introduction: ALS is a fatal neurodegenerative disease. However, patients show variability in the length of survival after symptom onset. Understanding the mechanisms of long survival could lead to possible avenues for therapy. Areas covered: This review surveys the reported length of survival in ALS, the clinical features that predict survival in individual patients, and possible factors, particularly genetic factors, that could cause short or long survival. The authors also speculate on possible mechanisms. Expert opinion: A small number of known factors can explain some variability in ALS survival. However, other disease-modifying factors likely exist. Factors that alter motor neurone vulnerability and immune, metabolic and muscle function could affect survival by modulating the disease process. Knowing these factors could lead to interventions to change the course of the disease. The authors suggest a broad approach is needed to quantify the proportion of variation survival attributable to genetic and non-genetic factors and to identify and estimate the effect size of specific factors. Studies of this nature could not only identify novel avenues for therapeutic research but also play an important role in clinical trial design and personalized medicine.

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“…Recent studies suggest there is a strong metabolic component in ALS pathogenesis, being that the majority of patients show hypermetabolism, rapid weight loss, and low body mass index [5][6][7]. Moreover, even though obesity represents the second preventable mortality cause worldwide [8], there is growing evidence that being overweight or obese provides a survival advantage in ALS patients [9].…”

Section: Introductionmentioning

confidence: 99%

Effect of Leptin Treatment in a Mouse Model of Tdp-43 Proteinopathy

Ferrer-Donato¹,

Contreras²,

Fernández³

et al. 2021

Preprint

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Amyotrophic Lateral Sclerosis (ALS) is an irreversible neurodegenerative disease with no known cure. Recent studies suggest a strong metabolic component in ALS pathogenesis and have shown an inverse relationship between leptin levels and ALS progression, although the effects of leptin as a treatment have not yet been studied. Therefore, we aim to examine whether the acute treatment with leptin has beneficial effects on brain pathology and cognitive function in the transgenic TDP43A315T line of ALS. Mice were treated intranasally (IN) with 0.03mg/kg of leptin or vehicle (VH) daily for 7 days. Data showed a progressive decline in body weight and motor coordination in TDP43A315T mice. Moreover, Lep-treated TDP43A315T mice showed an earlier disease onset, along with an improvement in motor performance. Altered levels of some of the adipokines and metabolic proteins studied were found in TDP43A315T mice, which were differently expressed among Lep-treated and VH-treated animals. Furthermore, some correlations were found among the serum levels of this proteins in WT and TDP43A315T mice. As far as we know, this is the first pilot study to provide evidence of the therapeutic effect of leptin treatment in a mice model of ALS, although further studies are needed to expound on the underlying mechanisms.

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

Cited by 33 publications

References 47 publications

Prevalence of multimorbidity and its impact on survival in people with motor neuron disease

Prevalence of multimorbidity and its impact on survival in people with motor neuron disease

What do we know about the variability in survival of patients with amyotrophic lateral sclerosis?

Effect of Leptin Treatment in a Mouse Model of Tdp-43 Proteinopathy

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