Risk factors associated with amyotrophic lateral sclerosis based on the observational study: a systematic review and meta-analysis

Abstract

ObjectiveAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively.MethodsWe searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis.ResultsA total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses.ConclusionsHead trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies.INPLSY registration numberhttps://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.

History of ALS and the competing theories on pathogenesis: IFCN handbook chapter

“…Numerous non-genetic risk factors for ALS have been considered over many decades, but few have met the rigors required by epidemiologists, and replicable definitive non-genetic risk factors of ALS have not been identified ( Duan et al, 2023 ). Head trauma, physical activity, electric shock, military service, pesticides, and lead, amongst others, are considered potential risk factors for ALS onset and progression ( Andrew et al, 2021 , Beaudin et al, 2022 , Zhu et al, 2023 ). But, older age and male sex so far remain the only definitive non-genetic risks for ALS ( Longinetti and Fang, 2019 ).…”

The influence of environmental risk factors in the development of ALS in the Mediterranean Island of Cyprus

“…It is believed that sALS is equally influenced by the interaction of multiple genes (polygenic traits) and environmental risk factors (11). Numerous studies have focused on the environmental risk factors that are positively associated with ALS (12)(13)(14)(15)(16)(17)(18). However, dietary factors such as vitamin E supplements and polyunsaturated fatty acids consumption, as well as type 2 diabetes, have shown an inverse association with ALS since they were associated with a lower risk of ALS (11,16,19).…”