Amyotrophic Lateral Sclerosis Mortality Research Articles

Premorbid lipid levels and long-term risk of ALS—a population-based cohort study

Objective To assess the temporal relationship between premorbid lipid levels and long-term amyotrophic lateral sclerosis (ALS) risk. Methods From Norwegian cardiovascular health surveys (1974–2003), we collected information on total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, and other cardiovascular risk factors. ALS incidence and mortality were identified through validated Norwegian health registries. The relation between premorbid lipid levels and ALS risk was assessed by Cox regression models. Results Out of 640,066 study participants (51.5% females), 974 individuals (43.5% females) developed ALS. Mean follow-up time was 23.7 (SD 7.1) years among ALS cases. One mmol/l increase in LDL-C was associated with 6% increase in risk for ALS (hazard ratio 1.06 [95% CI: 1.01–1.09]). Higher levels of TC and TG were also associated with increased ALS risk, but only within the last 6–7 years prior to ALS diagnosis or death. No association between HDL-C and ALS risk was found. Adjusting for body mass index, birth cohort, smoking, and physical activity did not alter the results. Conclusions Higher levels of LDL-C are associated with increased ALS risk over 40 years later, compatible with a causal relationship. The temporal relationship between TG, TC, and ALS risk suggests that increased levels of these lipid biomarkers represent consequences of ALS.

Environmental risk scores of persistent organic pollutants associate with higher ALS risk and shorter survival in a new Michigan case/control cohort

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal, progressive neurogenerative disease caused by combined genetic susceptibilities and environmental exposures. Identifying and validating these exposures are of paramount importance to modify disease...

Genetic Modifiers of Age at Onset for Amyotrophic Lateral Sclerosis: A Genome-Wide Association Study.

Age at onset (AAO) is an essential clinical feature associated with disease progression and mortality in amyotrophic lateral sclerosis (ALS). Identification of genetic variants and environmental risk factors influencing AAO of ALS could help better understand the disease's biological mechanism and provide clinical guidance. However, most genetic studies focused on the risk of ALS, while the genetic background of AAO is less explored. This study aimed to identify genetic and environmental determinants for AAO of ALS. We performed a genome-wide association analysis using a Cox proportional hazards model on AAO of ALS in 10,068 patients. We further conducted colocalization analysis and in-vitro functional exploration for the target variants, as well as Mendelian randomization analysis to identify risk factors influencing AAO of ALS. The total heritability of AAO of ALS was ~0.16 (standard error [SE] = 0.03). One novel locus rs2046243 (CTIF) was significantly associated with earlier AAO by ~1.29 years (p = 1.68E-08, beta = 0.10, SE = 0.02). Functional exploration suggested this variant was associated with increased expression of CTIF in multiple tissues including the brain. Colocalization analysis detected a colocalization signal at the locus between AAO of ALS and expression of CTIF. Causal inference indicated higher education level was associated with later AAO. These findings improve the current knowledge of the genetic and environmental etiology of AAO of ALS, and provide a novel target CTIF for further research on ALS pathogenesis and potential therapeutic options to delay the disease onset. ANN NEUROL 2023;94:933-941.

Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study

BackgroundWhile systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence. MethodsWe used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3–7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. ResultsIn an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose–response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76). ConclusionsHigher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition noteworthy for upper and lower motor neuron death. Involvement of respiratory motor neuron pools leads to progressive pathology. These impairments include decreases in neural activation and muscle coordination, progressive airway obstruction, weakened airway defenses, restrictive lung disease, increased risk of pulmonary infections, and weakness and atrophy of respiratory muscles. These neural, airway, pulmonary, and neuromuscular changes deteriorate integrated respiratory-related functions including sleep, cough, swallowing, and breathing. Ultimately, respiratory complications account for a large portion of morbidity and mortality in ALS. This state-of-the-art review highlights applications of respiratory therapies for ALS, including lung volume recruitment, mechanical insufflation-exsufflation, non-invasive ventilation, and respiratory strength training. Therapeutic acute intermittent hypoxia, an emerging therapeutic tool for inducing respiratory plasticity will also be introduced. A focus on emerging evidence and future work underscores the common goal to continue to improve survival for patients living with ALS.

Long-term air pollution and risk of amyotrophic lateral sclerosis mortality in the Women's Health Initiative cohort

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with no cure. Although the etiology of sporadic ALS is largely unknown, environmental exposures may affect ALS risk. ObjectiveWe investigated relationships between exposure to long-term ambient particulate matter (PM) and gaseous air pollution (AP) and ALS mortality. MethodsWithin the Women's Health Initiative (WHI) cohort of 161,808 postmenopausal women aged 50–79 years at baseline (1993–1998), we performed a nested case-control study of 256 ALS deaths and 2486 matched controls with emphasis on PM constituents (PM2.5, PM10, and coarse PM [PM10-2.5]) and gaseous pollutants (NOx, NO2, SO2, and ozone). Time-varying AP exposures estimates were averaged 5, 7.5, and 10 years prior to ALS death using both a GIS-based spatiotemporal generalized additive mixed model and ordinary kriging (empirical and multiple imputation, MI). Conditional logistic regression was used to estimate the relative risk of ALS death. ResultsIn general, PM2.5 and PM10-related risks were not significantly elevated using either method. However, for PM10-2.5, odds ratios (ORs) were >1.0 for both methods at all time periods using MI and empirical data for PM10-2.5 (coarse) except for 5 and 7.5 years using the kriging method with covariate adjustment. ConclusionThis investigation adds to the body of information on long-term ambient AP exposure and ALS mortality. Specifically, the 2019 US Environmental Protection Agency (EPA) Integrated Science Assessment summarized the neurotoxic effects of PM2.5, PM10, and PM10-2.5. The conclusion was that evidence of an effect of coarse PM is suggestive but the data is presently not sufficient to infer a causal relationship. Further research on AP and ALS is warranted. As time from symptom onset to death in ALS is ∼2–4 years, earlier AP measures may also be of interest to ALS development. This is the first study of ALS and AP in postmenopausal women controlling for individual-level confounders.

A new method for estimating under-recruitment of a patient registry: a case study with the Ohio Registry of Amyotrophic Lateral Sclerosis

We developed a disease registry to collect all incident amyotrophic lateral sclerosis (ALS) cases diagnosed during 2016–2018 in Ohio. Due to incomplete case ascertainment and limitations of the traditional capture-recapture method, we proposed a new method to estimate the number of cases not recruited by the Registry and their spatial distribution. Specifically, we employed three statistical methods to identify reference counties with normal case-population relationships to build a Poisson regression model for estimating case counts in target counties that potentially have unrecruited cases. Then, we conducted spatial smoothing to adjust outliers locally. We validated the estimates with ALS mortality data. We estimated that 119 total cases (95% CI [109, 130]) were not recruited, including 36 females (95% CI [31, 41]) and 83 males (95% CI [74, 99]), and were distributed unevenly across the state. For target counties, including estimated unrecruited cases increased the correlation between the case count and mortality count from r = 0.8494 to 0.9585 for the total, from 0.7573 to 0.8270 for females, and from 0.6862 to 0.9292 for males. The advantage of this method in the spatial perspective makes it an alternative to capture-recapture for estimating cases missed by disease registries.

Amyotrophic lateral sclerosis mortality rates in Latin America and the Caribbean: a meta-analysis

Background: Recent studies have described a low occurrence of Amyotrophic Lateral Sclerosis (ALS) in Latin America. Significant differences in ALS risk have been reported among ethnic populations in the region. We conducted a meta-analysis using population-based data to describe ALS mortality rates in Latin America. We explored sources of heterogeneity among key covariates. Methods: National mortality registries from Latin American countries were searched to identify ALS deaths according to the International Classification of Diseases (ICD-9: code 335.2 and ICD-10: code G12.2). Crude and standardized mortality rates were calculated. A random-effect meta-analysis was conducted to estimate pooled mortality rates. Subgroup analysis was performed as a means of investigating heterogeneity. Results: Overall, 28,548 ALS deaths and 819 million person-years of follow-up (PYFU) from ten Latin American countries were considered. Standardized mortality varied among countries. The highest mortality rates were observed in Uruguay and Costa Rica at 1.3 and 1.2 per 100,000 PYFU, respectively. The pooled crude mortality rate was 0.38 (95%CI: 0.28–0.53) and the pooled standardized mortality was 0.62 (95%CI: 0.49–0.77) per 100,000 PYFU. Heterogeneity was high (I2: 99.9%, Cochran’s Q p < 0.001). Subgroup analysis showed a higher mortality rate among countries with a higher proportion of Caucasian populations and higher income levels. Conclusion: There is a lower ALS occurrence in Latin America compared to Europe and North America. This meta-analysis supports the hypothesis of a higher ALS risk among the Caucasian population. Further studies are needed to investigate the role of ancestral origins in ALS, taking socioeconomic status into consideration.

Long-Term Air Pollution and Risk of Amyotrophic Lateral Sclerosis Mortality in the Women's Health Initiative Cohort

Long-Term Air Pollution and Risk of Amyotrophic Lateral Sclerosis Mortality in the Women's Health Initiative Cohort

Incidence of and Mortality From Amyotrophic Lateral Sclerosis in National Football League Athletes

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; understanding ALS risk factors is a critical public health issue. To evaluate the incidence of and mortality from ALS in National Football League (NFL) athletes and to describe characteristics associated with ALS within this cohort. This population-based cohort study included all 19 423 NFL athletes who debuted between 1960 and 2019 and played 1 or more professional game. It was conducted between October 3, 2020, and July 19, 2021. Participation in the NFL, including playing 1 or more professional games. Cases of ALS and death information were identified based on public records from NFL statistics aggregators, news reports, obituaries, and National Death Index results. The standardized incidence ratio and the standardized mortality ratio were calculated based on data acquired from surveillance studies of ALS accounting for age, sex, and race. Secondary analyses examined the association of body mass index, NFL career duration, race, birth location, and markers of fame, using a nested case-control design, matching athletes with ALS to athletes without ALS, by NFL debut year. A total of 19 423 male former and current NFL players (age range, 23-78 years) were included in this cohort study and were followed up for a cumulative 493 168 years (mean [SD] follow-up, 30.6 [13.7] years). Thirty-eight players received a diagnosis of ALS, and 28 died during the study time frame, representing a significantly higher incidence of ALS diagnosis (standardized incidence ratio, 3.59; 95% CI, 2.58-4.93) and mortality (standardized mortality ratio, 3.94; 95% CI, 2.62-5.69) among NFL players compared with the US male population, adjusting for age and race. Among NFL athletes, nested-case-control analyses found that those who received a diagnosis of ALS had significantly longer careers (mean [SD] duration, 7.0 [3.9] years) than athletes without ALS (mean [SD] duration, 4.5 [3.6] years; odds ratio, 1.2; 95% CI, 1.1-1.3). There were no differences in ALS status based on proxies of NFL fame, body mass index, position played, birth location, or race. The age-, sex-, and race-adjusted incidence of and mortality from ALS among all NFL players who debuted between 1960 and 2019 were nearly 4 times as high as those of the general population. Athletes with a diagnosis of ALS had longer NFL careers than those without ALS, suggesting an association between NFL duration of play and ALS. The identification of these risk factors for ALS helps to inform the study of pathophysiological mechanisms responsible for this fatal neurodegenerative disease.

Incidence, prevalence and mortality of amyotrophic lateral sclerosis in Taiwan

Incidence, prevalence and mortality of amyotrophic lateral sclerosis in Taiwan

Amyotrophic lateral sclerosis mortality rates among ethnic groups in a predominant admixed population in Latin America: a population-based study in Ecuador

Current evidence suggests heterogeneity of amyotrophic lateral sclerosis (ALS) among geographic areas and populations. Lower mortality rates have been reported in admixed populations compared to European origin populations. We aimed to describe and compare ALS mortality rates among ethnic groups using a population-based approach in a multiethnic country. Annual mortality cause registers were searched to determine ALS deaths from the National Institute of Statistics and Censuses in Ecuador (INEC) from 1990 to 2016. Mid-year population was considered for each year. The time trend was assessed using a negative binomial regression. Rate ratio statistics were performed to compare the age and sex standardized rates based on the 2010 US population among ethnic groups. Overall, 570 ALS deaths were identified. ALS mortality showed an age-related profile with a peak between 55 and 70 years. After age–sex standardization on the 2010 US population, mortality rate was 0.33 (CI 0.30–0.36) per 100,000. The time trend showed an increase of ALS mortality (p < 0.001). There was no statistical difference in age–sex standardized mortality rates per 100,000 when admixed was compared to white (p = 0.231) and black (p = 0.125). Differences reached statistical significance between admixed and other ethnics (p = 0.015). Our population-based study supports the hypothesis that ALS occurrence is lower in predominant admixed populations from Latin America compared to European and Northern American populations. Further studies are needed to clarify the role of ancestral origin in ALS susceptibility.

Respiratory Deficiency in the Optn−/−Mouse, A Novel Model of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a devastating and fatal neurodegenerative disease with no current cure. Patients with ALS die 3–5 years after diagnosis when they ultimately succumb to inadequate ventilation, hypoxia, and respiratory failure. Several genes associated with ALS have recently been discovered. One of these genes encodes optineurin (OPTN) which is associated with neurodegeneration in both ALS and glaucoma. Optineurin has multiple roles in various biochemical pathways such as regulation of inflammation and autophagy. Through these functions, OPTN appears to be neuroprotective but the exact mechanism by which loss of OPTN results in progressive neural degeneration and respiratory failure in ALS is still unclear.Since respiratory pathology is a significant cause of morbidity and mortality in ALS, this study sought to characterize the respiratory pathology in a novel ALS mouse model – the Optn−/− mouse. The hypothesis driving this work is that the Optn−/− mouse has respiratory insufficiency due to degeneration of the respiratory motor unit – motor neuron, nerve, neuromuscular junction and muscle. Whole body plethysmography (WBP) was used to assess breathing at baseline and during a respiratory challenge with hypercapnic and hypoxic conditions (FiCO2: 0.07, FiO2: 0.10; nitrogen balance). During the respiratory challenge, compared to the WT mice, Optn−/− mice had significantly lower peak inspiratory flow and peak expiratory flow. Peak inspiratory flow and peak expiratory flow are indirect measures of inspiratory and expiratory muscle strength. Furthermore, throughout the challenge period Optn−/− mice spent a greater amount of time in apnea indicating pathology in the respiratory control centers. The weakness and pathology in control of breathing during the respiratory challenge progresses as the mice age. Post mortem immunohistochemical studies of the neuromuscular junctions within the diaphragm showed that Optn−/− mice had fragmented synaptotagmin staining indicating presynaptic degeneration. Finally, the hypoglossal nerves of Optn−/− mice had significantly reduced g‐ratio which indicates pathology and decompaction of myelin sheaths. In conclusion, the Optn−/− ALS mouse model displays respiratory insufficiency, aberrant control of breathing, and increased nerve demyelination.Support or Funding InformationR21 NS098131‐02 (MKE) and K08HD077040‐07 (MKE)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Genioglossus activation during maximal sniff manoeuvres: Is upper airway function relevant in the clinical assessment of inspiratory and expiratory muscle strength?

Genioglossus activation during maximal sniff manoeuvres: Is upper airway function relevant in the clinical assessment of inspiratory and expiratory muscle strength?

Coffee, tea, and caffeine intake and amyotrophic lateral sclerosis mortality in a pooled analysis of eight prospective cohort studies.

Caffeine is associated with a lower risk of some neurological diseases, but few prospective studies have investigated caffeine intake and risk of amyotrophic lateral sclerosis (ALS) mortality. We therefore determined associations between coffee, tea and caffeine intake, and risk of ALS mortality. We conducted pooled analyses of eight international, prospective cohort studies, including 351565 individuals (120688 men and 230877 women). We assessed coffee, tea and caffeine intake using validated food-frequency questionnaires administered at baseline. We used Cox regression to estimate study- and sex-specific risk ratios and 95% confidence intervals (CI) for ALS mortality, which were then pooled using a random-effects model. We conducted analyses using cohort-specific tertiles, absolute common cut-points and continuous measures of all exposures. During follow-up, 545 ALS deaths were documented. We did not observe statistically significant associations between coffee, tea or caffeine intake and risk of ALS mortality. The pooled multivariable risk ratio (MVRR) for ≥3 cups per day vs. >0 to <1 cup per day was 1.04 (95% CI, 0.74-1.47) for coffee and 1.17 (95% CI, 0.77-1.79) for tea. The pooled MVRR comparing the highest with the lowest tertile of caffeine intake (mg/day) was 0.99 (95% CI, 0.80-1.23). No statistically significant results were observed when exposures were modeled as tertiles or continuously. Our results do not support associations between coffee, tea or total caffeine intake and risk of ALS mortality.

Amyotrophic Lateral Sclerosis Mortality in the United States, 2011–2014

Background: The International Classification of Disease, 10th Revision (ICD-10) did not include a code specific for Amyotrophic lateral sclerosis (ALS) until 2017. Instead, code G12.2 included both ALS and other motor neuron diseases (MND). Our objective was to determine US mortality rates for ALS exclusively by excluding other MND and progressive supranuclear palsy. Methods: All mortality data coded as G12.2 under the pre-2017 rubric were obtained for 2011–2014. Deaths without ALS listed in one of the un-coded cause-of-death fields were excluded. ALS death rates per 100,000 persons were age-adjusted to the 2000 US standard population using the direct method. Results: The proportion of excluded records coded G12.2 but not ALS was 0.21, resulting in 24,328 ALS deaths. The overall age-adjusted mortality rate was 1.70 (95% CI 1.68–1.72). The rate among males was 2.09 (95% CI 2.05–2.12) and females was 1.37 (95% CI 1.35–1.40). The overall rate among whites was 1.84, blacks 1.03, and other races 0.70. For both sexes and all races, the rate increased with age and peaked among 75–79 year-olds. Rates tended to be greater in states at higher latitudes. Conclusions: Previous reports of ALS mortality in the United States showed similar age, sex, and race distributions but with greater age-adjusted mortality rates due to the inclusion of other diseases in the case definition. When using ICD-10 data collected prior to 2017, additional review of multiple-cause of death data is required for the accurate estimation of ALS deaths.

Exercise Training as a Therapeutic Potential for Respiratory Muscle Weakness in Patients with Amyotrophic Lateral Sclerosis

PURPOSE Amyotrophic lateral sclerosis (ALS) is a devastating, incurable disease with five year mortality of higher than 95% mainly due to respiratory failure. Our goal was to investigate existing literature with attempts to improve ALS symptoms and mortality. METHODS A systemic search in PUBMED was performed to identify research papers and selected articles published in peer-reviewed journals. RESULTS This review outlined the two major sources of reactive oxygen species (ROS) that plays an important role on respiratory muscle weakness in ALS, which are mitochondria and NADPH oxidase. Previous animal studies have demonstrated that blocking sources of ROS enhanced respiratory muscle function and increased life span. We further discussed multiple therapeutic approaches to slow down the disease progression of ALS patients, including diaphragm pacing and intermittent hypoxia training. These previous approaches have suggested that exercise training might have beneficial impacts on the ALS patients. Regardless, exercise training, in the past years, has not been recommended due to its potential effect on accelerating disease progression. The impacts of training may benefit or harm the individuals depending on the training intensity and type of exercise (i.e. aerobic vs. resistance training). CONCLUSIONS Our systemic review suggests that excess ROS plays an important role in the pathogenesis of ALS, and exercise training might delay disease progression and symptoms. However, training effect of exercise on ALS patients has remained unclear. 색인어: 루게릭병, í˜¸í¡ë¶€ì „, ìš´ë™í›ˆë ¨, ì‚°í™”ì  ìŠ¤íŠ¸ë ˆìŠ¤ Keywords: Amyotrophic lateral sclerosis, Respiratory failure, Exercise training, Oxidative stress

Blood hemoglobin A1c levels and amyotrophic lateral sclerosis survival

BackgroundThere are inconsistences regarding the correlation between diabetes or fasting blood glucose concentrations and the risk and survival of amyotrophic lateral sclerosis (ALS) in the previous studies. Moreover, the association between hemoglobin A1c (HbA1c) levels, which reflect long-term glycemic status, and ALS survival was not examined.MethodsA prospective cohort study including 450 Chinese sporadic ALS patients (254 men and 196 women; mean age: 55.4 y). We identified 223 deaths during average 1.6 years of follow-up. We assessed levels of fasting HbA1c (primary exposure) and glucose (secondary exposure) via ion exchange high-performance liquid chromatography and hexokinase/glucose-6-pgosphate dehydrogenase methods, respectively. Multivariate Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ALS mortality across the exposures.ResultsOur results indicated that, higher levels of HbA1c, but not fasting blood glucose concentrations, were significantly associated with higher risks of mortality. The adjusted HR was 1.40 (95% confidence interval (95% CI): 1.02–1.99) for HbA1c of 5.7–6.4%, and 2.06 (95% CI: 1.07–3.96) for HbA1c ≥6.5%, relative to HbA1c <5.7% (P trend =0.01), after adjustment for age, smoking, obesity, disease severity, site of onset, lifestyle, and other potential confounders. The adjusted HR was 1.38 (95% CI: 0.81–2.35, P trend =0.13) for fasting glucose concentrations ≥7.0 mmol/L vs <5.6 mmol/L. We did not observe any significant interactions between HbA1c levels and age, sex, smoking, body mass index, rate of disease progression of ALS, and site of onset (P-interactions >0.05 for all).ConclusionIn this prospective study, we observed that individuals with higher HbA1c levels at the baseline had higher risk of mortality, which is independent of other known risk factors.

Mortality from Amyotrophic Lateral Sclerosis and Parkinson's Disease Among Different Occupation Groups - United States, 1985-2011.

Amyotrophic lateral sclerosis (ALS) and Parkinson's disease, both progressive neurodegenerative diseases, affect >1 million Americans (1,2). Consistently reported risk factors for ALS include increasing age, male sex, and cigarette smoking (1); risk factors for Parkinson's disease include increasing age, male sex, and pesticide exposure, whereas cigarette smoking and caffeine consumption are inversely associated (2). Relative to cancer or respiratory diseases, the role of occupation in neurologic diseases is much less studied and less well understood (3). CDC evaluated associations between usual occupation and ALS and Parkinson's disease mortality using data from CDC's National Institute for Occupational Safety and Health (NIOSH) National Occupational Mortality Surveillance (NOMS), a population-based surveillance system that includes approximately 12.1 million deaths from 30 U.S. states.* Associations were estimated using proportionate mortality ratios (PMRs), standardizing indirectly by age, sex, race, and calendar year to the standard population of all NOMS deaths with occupation information. Occupations associated with higher socioeconomic status (SES) had elevated ALS and Parkinson's disease mortality. The shifts in the U.S. workforce toward older ages and higher SES occupations† highlight the importance of understanding this finding, which will require studies with designs that provide evidence for causality, detailed exposure assessment, and adjustment for additional potential confounders.

Occupational exposure and amyotrophic lateral sclerosis in a prospective cohort

ObjectiveTo prospectively study suspected occupational risk factors for amyotrophic lateral sclerosis (ALS).MethodsFor this case–cohort analysis within the prospective Netherlands Cohort Study, 58 279 men and 62 573 women aged 55–69...