Amyotrophic Lateral Sclerosis

Prospective Epidemiological Study of ALS

This project looks at the relationships between lifestyle factors and risk of amyotrophic lateral sclerosis (ALS). In a previous project, based on the follow-up of nearly one million participants in the Cancer Prevention Study II, we documented a 60% lower risk of ALS among men and women who reported regular use of vitamin E specific supplements as compared with non-users. This and other results which have important potential implications for the prevention of ALS need to be confirmed in a separate, large and rigorous prospective study. For this purpose, we plan to document ALS incidence and mortality in five large and well-established prospective cohorts – the Nurses’ Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Cancer Prevention Study II Nutrition (CPS IIN), the Multiethnic Cohort (MEC), and the NIH-American Association of Retired Persons Diet and Health Study (AARP-DH) — comprising a total of over one million men and women. Primary aims include the investigation of the associations between risk of ALS and use of antioxidant vitamins, non-steroidal anti-inflammatory drugs (NSAIDs) and cigarette smoking. In addition, we will explore the association between dietary factors and ALS risk. The main strengths of the proposed investigation are its prospective design and the availability of detailed, validated and updated exposure information in some of the cohorts. Further, by taking advantage of these cohorts with many years of follow-up already accumulated, we will be able with a modest budget and in a few years to achieve results which would otherwise require a much longer and more expensive investigation.

Prospective Study of ALS Mortality Among World War II, Korea, and Vietnam Veterans

Recent reports have focused attention on a possible link between military service in the first Gulf War and an increased risk of ALS. In a preliminary study we found a significant increase in ALS mortality among military personnel deployed in World War II, Korea, and Vietnam. Further, we found a strong inverse association between regular use of specific vitamin E supplements and ALS mortality.

This study examines whether men who served in the military during WWII, Korea, or Vietnam have a higher risk of ALS mortality as compared with men who did not serve, and to examine the association between use of vitamin E supplements and ALS risk. To address these issues, we will use information collected on 508,334 men participating in the CPS II cohort, as well as a follow up through the National Death Index.

The specific questions we are addressing are as follows: 1. Is ALS mortality higher among men who served in the military before the first Gulf war than among men who were never enrolled, and, if so, is this increased mortality explained by differences in lifestyle such as smoking, diet, use of vitamin supplements, or occupation after military service? 2. Among men who served in the military, is ALS mortality higher among men who served during wartime? Specifically, we will compare ALS mortality among men who served during WWII, Korea, or Vietnam with that of men who served only during peacetime. Further, we will explore associations with country or region of service. 3. Is ALS mortality lower among men who regularly (at least 15 days per month) use specific vitamin E supplements than among men who do not use these supplements? We will examine this question overall and in analyses restricted to men who served in the military. Further, we are examining the association between duration of use of specific vitamin E supplements and ALS mortality.