Objective:

We examined the relationship between military service and ALS survival while considering occupational lead exposure.

Background:

Military service has been associated with increased amyotrophic lateral sclerosis (ALS) incidence. Prior studies investigating the impact of military-related factors on ALS survival have yielded mixed results and have not disentangled the effect of lead from military service, despite lead exposure being common in the military and potentially associated with ALS progression.

Design/Methods:

We collected clinical measures and self-reported occupational history including military occupations from 135 ALS patients enrolled in the international CReATe PGB study in 2015-2019. We determined lead exposure from military and civilian occupations using a job-exposure matrix and the military-occupational-classification crosswalk. We evaluated survival using Cox proportional hazard models, considering sex, age of onset, site of symptom onset, smoking, and BMI as covariates.

Results:

Among the 135 ALS cases, 38 reached a survival endpoint (death or permanent assisted ventilation), and median survival was 3.6 years. Among 23 military veterans, 14 had military occupational lead exposure. Among 112 non-veterans, 13 had a lead-exposed civilian occupation. Results presented here are adjusted for age at onset only; further adjustment did not meaningfully change the estimates. Excluding lead exposure, military service was associated with a hazard ratio (HR) of 0.59 (95%CI: 0.23-1.54), and adjustment for lead pronounced this effect (HR=0.36 , 95%CI: 0.13-1.00). The result was similar when restricted to those without lead exposure (HR=0.23, 95%CI: 0.03-1.70). Lead exposure itself was associated with shorter survival (HR=3.25, 95%CI: 1.45-7.28).

Conclusions:

Results suggest that military service prior to onset of ALS is associated with longer survival following ALS onset, an effect that is more pronounced after accounting for occupational lead exposure. This association is independent of other prognostic factors and suggests “military service” may be too broad to capture the variance of multiple exposures. Supported by U54NS092091, R01TS00024, T32ES007069, and P30ES000002