Risk factors and amyotrophic lateral sclerosis : an epidemiologic approach

Amyotrophic Lateral Sclerosis (ALS) is a debilitating and rare disorder; progressively the patient’s muscles go into paralyses limiting their ability to walk, do day-to-day tasks, and eat. This thesis covers risk factors related to ALS. In Sweden, we investigated different types of head injuries, fractures and occupational metal and chemical exposures (using a job exposure matrix). In the United States, we looked at different levels of selenium (Se), zinc (Zn), copper (Cu) and manganese (Mn) found in human blood. Study I investigates severe head injury and ALS within the Swedish population. Additionally, we investigated repeated head injury and subtypes of head injury and how these are associated with the risk of ALS. We found that there was an association with severe head injury and the risk of ALS ≤ 1 year before diagnosis. No associations were found > 3 years before ALS diagnosis suggesting no strong support for the association between head injury and ALS. Study II investigates blood levels of trace metals (Se, Zn, Cu, and Mn) and the risk of ALS in United States military veterans. Specifically, we examined the risk of ALS with these metals, how ALS and metal associations varied by clinical features, and how lead effected the associations of metals and ALS. Interestingly, we found inverse associations with Se and Zn in relation to the risk of ALS. Cu was positively associated with ALS, although, adjustment for Pb attenuated this association. We found several inverse associations with Se and ALS, and a few with Zn and ALS by different clinical features. Study III investigates occupational exposures and the risk of ALS in the Swedish population. Uniquely, we used the Nordic Occupational Cancer Study Job Exposure Matrix to identify occupational exposures. We did not find occupational exposures to be associated with the risk of ALS in the general population. However, we did find a positive association with formaldehyde and an inverse association with methylene chloride with the risk of ALS; this was only among those that were 65 years of age or younger. Study IV investigates the association of the incidence of ALS with fractures; we examined any fracture (minus head and face), osteoporotic/non-osteoporotic fractures, and fractures related/not related to trauma. We found that all examined fractures were associated with an increased incidence of ALS. Any fractures (minus head and face) were consistently associated with a higher incidence of ALS from one to eighteen years after fracture diagnosis. In conclusion, our studies show that certain risk factors for ALS can offer insight into the disease etiology and pathophysiology. Bone health is important in relation to ALS and supplementation of Se and Zn might be beneficial for ALS patients. LIST OF SCIENTIFIC PAPERS I. Peters, TL, Fang, F, Weibull, CE, Sandler, DP, Kamel, F, Ye, W. Severe Head Injury and Amyotrophic Lateral Sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013;14:267-72 doi: 10.3109/21678421.2012. 754043. II. Peters, TL, Beard, JD, Umbach, DM, Allen, K, Keller, J, Mariosa, D, Sandler, DP, Schmidt, S, Fang, F, Ye, W, Kamel, F. Blood Levels of Trace Metals and Amyotrophic Lateral Sclerosis. Neurotoxicology, in press. III. Peters, TL, Kamel, F, Lundholm, C, Feychting, M, Weibull, CE, Sandler, DP, Wiebert, P, Sparén, P, Ye, W, Fang, F. Occupational Exposures and the Risk of Amyotrophic Lateral Sclerosis. Manuscript submitted. IV. Peters, TL, Weibull, CE, Fang, F, Sandler, DP, Lambert, PC, Ye, W, Kamel, F. Association of Fractures with the Incidence of Amyotrophic Lateral Sclerosis. Manuscript. CONTENTS