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Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?

Multiple studies have shown that antecedent diseases are less prevalent in amyotrophic lateral sclerosis (ALS) patients than the general age-matched population, which suggests possible neuroprotection. Antecedent disease could be protective against ALS or, conversely, the asymptomatic early physiolo...

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Autores principales: Hollinger, Sabrina K., Okosun, Ike S., Mitchell, Cassie S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810157/
https://www.ncbi.nlm.nih.gov/pubmed/27065942
http://dx.doi.org/10.3389/fneur.2016.00047
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author Hollinger, Sabrina K.
Okosun, Ike S.
Mitchell, Cassie S.
author_facet Hollinger, Sabrina K.
Okosun, Ike S.
Mitchell, Cassie S.
author_sort Hollinger, Sabrina K.
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description Multiple studies have shown that antecedent diseases are less prevalent in amyotrophic lateral sclerosis (ALS) patients than the general age-matched population, which suggests possible neuroprotection. Antecedent disease could be protective against ALS or, conversely, the asymptomatic early physiological underpinnings of ALS could be protective against other antecedent disease. Elucidating the impact of antecedent disease on ALS is critical for assessing diagnostic risk factors, prognostic outcomes, and intervention timing. The objective of this study was to examine the relationship between antecedent conditions and ALS onset age and disease duration (i.e. survival). Medical history surveys for 1439 Emory ALS Clinic patients (Atlanta, GA, USA) were assessed for antecedent hypertension, hyperlipidemia, diabetes, obesity, asthma, arthritis, chronic obstructive pulmonary disease (COPD), thyroid, kidney, liver, and other non-ALS neurological diseases. The ALS onset age and disease duration are compared between the antecedent and non-antecedent populations using chi square, Kaplan–Meier, and ordinal logistic regression. When controlled for confounders, antecedent hypertension (high blood pressure), hyperlipidemia (high cholesterol), arthritis, COPD, thyroid disease, and non-ALS neurological disease are found to be statistically associated with a delayed ALS onset age, whereas antecedent obesity [body mass index (BMI) > 30] was correlated to earlier ALS onset age. With the potential exceptions of liver disease and diabetes (the latter without other common comorbid conditions), antecedent disease is associated with overall shorter ALS disease duration. The unique potential relationship between antecedent liver disease and longer ALS disease duration warrants further investigation, especially given liver disease was found to be a factor of 4–7 times less prevalent in ALS. Notably, most conditions associated with delayed ALS onset are also associated with shorter disease duration. Pathological homeostatic instability exacerbated by hypervigilant regulation (over-zealous homeostatic regulation due to too high regulatory feedback gains) is a viable hypothesis for explaining the early-life protection against antecedent disease and the overall lower antecedent disease prevalence in ALS patients; the later ALS onset age in patients with antecedent disease; and the inverse relationship between ALS onset age and disease duration.
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spelling pubmed-48101572016-04-08 Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom? Hollinger, Sabrina K. Okosun, Ike S. Mitchell, Cassie S. Front Neurol Neuroscience Multiple studies have shown that antecedent diseases are less prevalent in amyotrophic lateral sclerosis (ALS) patients than the general age-matched population, which suggests possible neuroprotection. Antecedent disease could be protective against ALS or, conversely, the asymptomatic early physiological underpinnings of ALS could be protective against other antecedent disease. Elucidating the impact of antecedent disease on ALS is critical for assessing diagnostic risk factors, prognostic outcomes, and intervention timing. The objective of this study was to examine the relationship between antecedent conditions and ALS onset age and disease duration (i.e. survival). Medical history surveys for 1439 Emory ALS Clinic patients (Atlanta, GA, USA) were assessed for antecedent hypertension, hyperlipidemia, diabetes, obesity, asthma, arthritis, chronic obstructive pulmonary disease (COPD), thyroid, kidney, liver, and other non-ALS neurological diseases. The ALS onset age and disease duration are compared between the antecedent and non-antecedent populations using chi square, Kaplan–Meier, and ordinal logistic regression. When controlled for confounders, antecedent hypertension (high blood pressure), hyperlipidemia (high cholesterol), arthritis, COPD, thyroid disease, and non-ALS neurological disease are found to be statistically associated with a delayed ALS onset age, whereas antecedent obesity [body mass index (BMI) > 30] was correlated to earlier ALS onset age. With the potential exceptions of liver disease and diabetes (the latter without other common comorbid conditions), antecedent disease is associated with overall shorter ALS disease duration. The unique potential relationship between antecedent liver disease and longer ALS disease duration warrants further investigation, especially given liver disease was found to be a factor of 4–7 times less prevalent in ALS. Notably, most conditions associated with delayed ALS onset are also associated with shorter disease duration. Pathological homeostatic instability exacerbated by hypervigilant regulation (over-zealous homeostatic regulation due to too high regulatory feedback gains) is a viable hypothesis for explaining the early-life protection against antecedent disease and the overall lower antecedent disease prevalence in ALS patients; the later ALS onset age in patients with antecedent disease; and the inverse relationship between ALS onset age and disease duration. Frontiers Media S.A. 2016-03-29 /pmc/articles/PMC4810157/ /pubmed/27065942 http://dx.doi.org/10.3389/fneur.2016.00047 Text en Copyright © 2016 Hollinger, Okosun and Mitchell. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Hollinger, Sabrina K.
Okosun, Ike S.
Mitchell, Cassie S.
Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title_full Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title_fullStr Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title_full_unstemmed Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title_short Antecedent Disease and Amyotrophic Lateral Sclerosis: What Is Protecting Whom?
title_sort antecedent disease and amyotrophic lateral sclerosis: what is protecting whom?
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810157/
https://www.ncbi.nlm.nih.gov/pubmed/27065942
http://dx.doi.org/10.3389/fneur.2016.00047
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