Abstract
Background: Sporadic amyotrophic lateral sclerosis (ALS) is probably caused by multiple genetic and environmental factors causing motor neuron degeneration.Although environmental risk factors have been extensively studied in ALS, most environmental risk factors are still unknown.Systematic reviews of the literature suggest this may be due to limitations in study design: most
... read more
risk factor studies had a hospital-based study design, which introduces the risk of referral bias. This source of bias can be eliminated in a population-based casecontrol study, which enables the provision of class I evidence according to the Armon criteria (1) for exogenous risk factor studies in ALS. Objectives: To determine the association between ALS and multiple exogenous factors: smoking; alcohol; education; medical history; medication use; nutrition; family history; hormonal factors; occupational history; occupational exposures (pesticides, metals, electrical accidents, etc.); physical activity. Methods: A population based study has been performed in the Netherlands between January 2006 and June 2011 (mean population 16,426,273; area 41,528 km2 ).Patients were ascertained from five sources.Diagnosis was made according to the El Escorial criteria.700 incident sporadic ALS patients and 2100 controls filled in questionnaires to obtain data about exogenous factors. Results: Multivariate analyses showed an increased risk of ALS in current smokers (OR 1.38; p = 0.04).Current smoking was also associated with shorter survival (hazard ratio of 1.51 (p = 0.02) adjusted for vital capacity, gender, age and site of onset).Current alcohol consumption was found to be an independent protective factor for ALS (OR = 0.52; p = 6.6x10-5 ), but did not have an effect on survival.Relatives of sporadic ALS patients had a mildly elevated risk of dementia (recurrence risk lambda 1.16; 95% CI: 1.01-1.33).The risk of Parkinson Disease (PD) was not elevated ( lambda 1.14; 95% CI: 0.83-1.55).A reduced risk of vascular diseases was found in relatives of sporadic ALS patients (stroke: lambda 0.94; 95% CI: 0.82-1.07 and myocardial infarction: lambda 0.87; 95% CI: 0.76-0.98).Longest job held in the agricultural sector is associated with an increased risk of developing ALS (OR 1.7; 95% CI: 1.01- 3.00, p = 0.045) (adjusted for smoking, use of alcohol, and age).Last job held in the agricultural sector is associated with ALS as well (OR 1.8; 95%CI: 1.1-3.1, p = 0.03).Subsequently a Job Exposure Matrix (JEM) was used, which enables the linking of occupations to profiles of environmental exposures by providing semi-quantitative assessments of exogenous exposures for each occupation.Mean lifetime occupational exposures to chromium, nickel, diesel motor exhaust, and mine dust were significantly higher in patients compared with controls.Exposure to pesticides was not significantly increased in patients. Results on the other exogenous factors will be presented, as well as the result of a multivariate analysis including all exogenous risk factors.Discussion and conclusions: Cigarette smoking, occupation in the agricultural sector, and a low level of education are risk factors for ALS.Current smoking is associated with a worse prognosis, alcohol consumption reduces the risk of ALS.Familial aggregation of ALS, dementia and PD is substantially lower than previously thought.The lowered risk of vascular diseases in relatives of ALS patients supports the view that a beneficial vascular risk profile increases ALS susceptibility.More risk factors will be analyzed and presented at the symposium.The multivariate analysis, including all exogenous risk factors, will determine which risk factors are independently associated with ALS.
show less
