Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis survival

Abstract

BackgroundMilitary veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases.MethodsWe followed 616 medical record-confirmed cases from enrollment (2005–2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment.ResultsWe observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73.ConclusionsAlthough most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.

Motor neuron disease mortality rates in U.S. states are associated with well water use

“…A Legionella -ALS hypothesis is supported by similarities in the descriptive epidemiology of Legionnaires’ disease and ALS: the peak incidence of both diseases occurs after age 50 years; both show a male predominance; and the only established behavioral risk factor for ALS, cigarette smoking, is a risk factor for infection with Legionella (63). Military veterans appear to have an increased risk for ALS, regardless of deployment status (64). That finding is intelligible because hospitalization for pneumonia, including that caused by Legionella , is many times more common in recruit than in civilian populations (65,66).…”

Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

“…1,2 A lower bound for the genetic contribution is given by the proportion of variance associated with common single-nucleotide polymorphisms (SNPs) genome-wide, the SNP-based heritability estimated as 8.5% (CI 95% = [7.5-9.5]) in Europeans 3 and 15% (CI 95% = [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]) in East Asians. 4 Epidemiological studies have also identified environmental and occupational risk factors, such as metal and pesticide exposure 5 and defense force occupation, 6,7 but generally studies are underpowered. 8 Hence, lifetime environmental exposures paired with genetic susceptibility likely contribute to an increased risk for ALS.…”

“…5 Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht 3584 CG, Netherlands. 6 Mater Research Institute, The University of Queensland, Brisbane, QLD 4101, Australia. 7 Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.…”

Neuropathological profile of long‐duration amyotrophic lateral sclerosis in military Veterans

“…Approximately 10% of ALS cases are classified as familial ALS, in which the disorder tends to be inherited in an autosomal dominant fashion (16,40), and numerous contributory genes have been identified (1). Other risk factors for the development of ALS include age (6), male gender (16) and military service (7,38,43,50,88). Despite differences in etiology, sporadic and familial ALS possess similar patterns of neuropathological degeneration (2).…”

“…Previous studies have noted that 50% of patients die within the first 3 years after disease onset, and only a small fraction of cases (~10%) survive 10 years or longer (24,63,74). Furthermore, large database and population-based studies have reported the median death in the US and Europe as approximately 3 years after disease onset (7,41,44,73). Previous studies have shown most cases of ALS have survival rates of less than 10 years and suggest that patients with ALS that survive 10 years or more represent a group with altered biology (23,87).…”