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Environmental exposures impact amyotrophic lateral sclerosis (ALS) risk and progression, a fatal and progressive neurodegenerative disease. Better characterization of these exposures is needed to decrease disease burden. To identify exposures in the residential setting that associate with ALS risk, survival, and onset segment. ALS and control participants recruited from University of Michigan completed a survey that ascertained exposure risks in the residential setting. ALS risk was assessed using logistic regression models followed by latent profile analysis to consider exposure profiles. A case-only analysis considered the contribution of the residential exposure variables via a Cox proportional hazards model for survival outcomes and multinomial logistic regression for onset segment, a polytomous outcome. This study included 367 ALS and 255 control participants. Twelve residential variables were associated with ALS risk after correcting for multiple comparison testing, with storage in an attached garage of chemical products including gasoline or kerosene (odds ratio (OR) = 1.14, padjusted < 0.001), gasoline-powered equipment (OR = 1.16, padjusted < 0.001), and lawn care products (OR = 1.15, padjusted < 0.001) representing the top three risk factors sorted by padjusted. Latent profile analysis indicated that storage of these chemical products in both attached and detached garages increased ALS risk. Although residential variables were not associated with poorer ALS survival following multiple testing corrections, storing pesticides, lawn care products, and woodworking supplies in the home were associated with shorter ALS survival using nominal p values. No exposures were associated with ALS onset segment. Residential exposures may be important modifiable components of the ALS susceptibility and prognosis exposome. [ABSTRACT FROM AUTHOR]

Background: Environmental exposures contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal and progressive neurological disease. Identification of these exposures is important for targeted screening and risk factor modification. Objective: To identify occupational exposures that are associated with a higher risk of ALS using both survey and standard occupational classification (SOC) coding procedures, and to highlight how exposure surveys can complement SOC coding. Methods: ALS participants and neurologically healthy controls recruited in Michigan completed a detailed exposure assessment on their four most recent and longest held occupations. Exposure scores were generated from the exposure survey, and occupations were assigned to SOC codes by experienced exposure scientists. Results: This study included 381 ALS and 272 control participants. ALS participants reported higher duration-adjusted occupational exposure to particulate matter (OR = 1.45, 95% CI 1.19–1.78, p < 0.001), volatile organic compounds (OR = 1.22, 95% CI 1.02–1.45, p = 0.029), metals (OR = 1.48, 95% CI 1.21–1.82, p < 0.001), and combustion and diesel exhaust pollutants (OR = 1.20, 95% CI 1.01–1.43, p = 0.041) prior to ALS diagnosis, when adjusted for sex, age, and military service compared to controls. In multivariable models, only occupational exposure to metals remained significant risk (OR = 1.56, 95% CI 1.11–2.20, p = 0.011), although in an adaptive elastic net model, particulate matter (OR = 1.203), pesticides (OR = 1.015), and metals (1.334) were all selected as risk factors. Work in SOC code "Production Occupations" was associated with a higher ALS risk. SOC codes "Building and Grounds Cleaning and Maintenance Occupations", "Construction and Extraction Occupations", "Installation, Maintenance, and Repair Occupations", and "Production Occupations" were all associated with a higher exposure to metals as determined using survey data. Discussion: Occupational exposure to particulate matter, volatile organic compounds, metals, pesticides, and combustion and diesel exhaust and employment in "Production Occupations" was associated with an increased ALS risk in this cohort. [ABSTRACT FROM AUTHOR]

Introduction: Environmental exposures strongly influence ALS risk and identification is needed to reduce ALS burden. Participation in hobbies and exercise may alter ALS risk and phenotype, warranting an assessment to understand their contribution to the ALS exposome., Methods: Participants with ALS and healthy controls were recruited from University of Michigan and self-completed a survey to ascertain hobbies, exercise, and avocational exposures. Exposure variables were associated with ALS risk, survival, onset segment, and onset age., Results: ALS (n = 400) and control (n = 287) participants self-reported avocational activities. Cases were slightly older (median age 63.0 vs. 61.1 years, p = 0.019) and had a lower educational attainment (p < 0.001) compared to controls; otherwise, demographics were well balanced. Risks associating with ALS after multiple comparison correction included golfing (odds ratio (OR) 3.48, p adjusted  = 0.004), recreational dancing (OR 2.00, p adjusted  = 0.040), performing gardening or yard work (OR 1.71, p adjusted  = 0.040) five years prior to ALS and personal (OR 1.76, p adjusted  = 0.047) or family (OR 2.21, p adjusted  = 0.040) participation in woodworking, and personal participation in hunting and shooting (OR 1.89, p adjusted  = 0.040). No exposures associated with ALS survival and onset. Those reporting swimming (3.86 years, p adjusted  = 0.016) and weightlifting (3.83 years, p adjusted  = 0.020) exercise 5 years prior to ALS onset had an earlier onset age., Discussion: The identified exposures in this study may represent important modifiable ALS factors that influence ALS phenotype. Thus, exposures related to hobbies and exercise should be captured in studies examining the ALS exposome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Amyotrophic 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 risk. We previously reported that persistent organic pollutants (POPs) associate with ALS risk and survival and aimed to replicate these findings in a new cohort., Method: Participants with and without ALS recruited in Michigan provided plasma samples for POPs analysis by isotope dilution with triple quadrupole mass spectrometry. ORs for risk models and hazard ratios for survival models were calculated for individual POPs. POP mixtures were represented by environmental risk scores (ERS), a summation of total exposures, to evaluate the association with risk (ERS risk ) and survival (ERS survival )., Results: Samples from 164 ALS and 105 control participants were analysed. Several individual POPs significantly associated with ALS, including 8 of 22 polychlorinated biphenyls and 7 of 10 organochlorine pesticides (OCPs). ALS risk was most strongly represented by the mixture effects of OCPs alpha-hexachlorocyclohexane, hexachlorobenzene, trans -nonachlor and cis -nonachlor and an interquartile increase in ERS risk enhanced ALS risk 2.58 times (p<0.001). ALS survival was represented by the combined mixture of all POPs and an interquartile increase in ERS survival enhanced ALS mortality rate 1.65 times (p=0.008)., Conclusions: These data continue to support POPs as important factors for ALS risk and progression and replicate findings in a new cohort. The assessments of POPs in non-Michigan ALS cohorts are encouraged to better understand the global effect and the need for targeted disease risk reduction strategies., Competing Interests: Competing interests: SAG: Listed as an inventor on a patent, issue number US10660895, held by University of Michigan titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics. Served on a DSMB and provided scientific advisory for a documentary about ALS. JB: Nothing to declare. D-GJ: Nothing to declare. BM: Nothing to declare. RJR: Nothing to declare. SB: Nothing to declare. ELF: Listed as an inventor on a patent, issue number US10660895, held by University of Michigan titled “Methods for Treating Amyotrophic Lateral Sclerosis” that targets immune pathways for use in ALS therapeutics., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)