Antecedent Disease Is Less Prevalent in Amyotrophic Lateral Sclerosis

Abstract

Background/Aims: Recent studies suggest that antecedent disease could impact the pathophysiology of the motoneuron disease Amyotrophic Lateral Sclerosis (ALS). We performed a case-control study to examine the prevalence of 11 antecedent diseases in ALS. Methods: Prevalence of antecedent disease in a 1,288 patient ALS population (Emory University ALS Clinic, Atlanta, Ga., USA) is compared to an age, gender, and geography-matched 7,561 subject control population using a statistical odds ratio (OR) with 95% confidence interval. Results: Association of ALS with odds of arthritis (OR = 0.14); non-ALS neurological disease (OR = 0.14); liver disease (OR = 0.19); chronic obstructive pulmonary disorder or COPD (OR = 0.23); kidney disease (OR = 0.32); adult asthma (OR = 0.39); diabetes (OR = 0.47); hypertension (OR = 0.56); obesity (OR = 0.6); hyperlipidemia or hypercholesterolemia (OR = 0.62); and thyroid disease (OR = 0.78). Conclusions: The prevalence of antecedent disease was overall less in the ALS population. We present two potential lines of inquiry to explain these results: (1) ‘Other disease as ALS protection' - antecedent diseases infer biochemical neuroprotection to ALS; (2) ‘ALS as other disease protection' - the underpinnings of ALS could infer protection to other diseases, possibly via the mechanism hypervigilant regulation or ‘too-high' regulatory feedback gains.

Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel

“…While there is evidence suggesting that ALS patients may be less likely than the general population to have cardiovascular disease and cardiovascular risk factors [17], no such difference was observed in our population between prevalent ALS patients and controls. The significantly lower prevalence of CKD among ALS patients compared to controls in our study is similar to a previous study, which found an odds ratio of 0.32 (95% CI 0.18-0.57) for ALS patients compared to age- and sex-matched controls [18]. A low CKD prevalence is also consistent with ALS patients' significantly lower BMI.…”

Characterization of the Contribution of Genetic Background and Gender to Disease Progression in the SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis: A Meta-Analysis

“…On a similar note, a recent study of non-familial clinical ALS patients showed that antecedent disease is substantially less prevalent among ALS patients, including metabolic disturbances like diabetes, obesity and thyroid disease, which suggests the possibility of neuroprotection—either “other disease is protective of ALS” or “ALS is protective of other disease” [32]. In fact, the pathophysiological process oscillations seen in models examining the SOD1 G93A underlying pathophysiology, suggest the possibility of “hypervigilant regulation” (in control theory a too-high feedback gain).…”

“…In fact, the pathophysiological process oscillations seen in models examining the SOD1 G93A underlying pathophysiology, suggest the possibility of “hypervigilant regulation” (in control theory a too-high feedback gain). Regulatory delays combined with the too-high feedback gain(s) of hypervigilant regulation, could ultimately result in system instabilities identified in the SOD1 G93A model that dramatically impact the onset and progression of ALS [32–34]. In short, genetic differences underlying cellular and systemic regulation could result in different ALS phenotypes, both in transgenic mouse models and in humans.…”

“…In short, genetic differences underlying cellular and systemic regulation could result in different ALS phenotypes, both in transgenic mouse models and in humans. Further assessment of pathology dynamics will help to distinguish phenotypic characteristics [32, 33, 35]. …”

An Assessment of Possible Neuropathology and Clinical Relationships in 46 Sporadic Amyotrophic Lateral Sclerosis Patient Autopsies

“…Nonetheless, autonomic [7, 8], blood pressure regulation [38–41], and even the potential role of antecedent disease and its affect on homeostasis [e.g. 42], has been previously discussed in the clinical literature. In summary, the widespread identification of overlapping pathological features quantified in this study lends credence to the hypothesis that ALS, FTD, as well as other neuropathologies, could potentially share interrelating etiologies [1, 2, 9], which may represent a larger motor-neurodegenerative-cognitive neuropathological continuum.…”