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Original Investigation |

Participation in Physical Activity and Risk for Amyotrophic Lateral Sclerosis Mortality Among Postmenopausal Women

Yvonne L. Eaglehouse, PhD, MPH1,2; Evelyn O. Talbott, DrPH2; Yuefang Chang, PhD3; Lewis H. Kuller, MD, DrPH2
[+] Author Affiliations
1Division of Cancer Prevention and Population Science, Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
2Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
3Department of Neurological Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
JAMA Neurol. 2016;73(3):329-336. doi:10.1001/jamaneurol.2015.4487.
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Importance  Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no known cause. Case studies primarily of athletes and several case-control studies have suggested that high levels of strenuous physical activity (PA) may increase the risk for ALS. This relationship has yet to be evaluated among women in population-based cohort studies.

Objective  To evaluate the relationship between PA and risk for ALS mortality in a large cohort of postmenopausal women.

Design, Setting, and Participants  The Women’s Health Initiative (WHI) enrolled 161 809 postmenopausal women, aged 50 to 79 years (mean [SD] age, 63.6 [7.24] years), between 1993 and 1998 into either a clinical trial or an observational study at 40 clinical research centers across the United States. We conducted a cohort study from November 2014 to September 2015 using baseline and mortality data during an average of 9.6 years of follow-up from the entire WHI cohort, through September 1, 2013 (with 1.1% lost to follow-up), to address whether there is a relationship between PA and ALS mortality.

Exposures  The WHI assessed frequency and duration of mild, moderate, and strenuous PA at baseline via self-administered questionnaire.

Main Outcomes and Measures  Underlying cause of death from ALS collected from death certificates.

Results  The WHI enrolled 161 809 women, of whom 165 died of ALS; women who died of ALS were older (median age, 66 years; interquartile range, 61-69 years) compared with the total WHI study population (median age, 63 years; interquartile range, 57-69 years). Age-adjusted ALS mortality rates varied from 7.4 (95% CI, 5.5-9.9)/100 000 person-years for no strenuous PA to 10.6 (95% CI, 5.6-20.0)/100 000 person-years for strenuous PA 3 or more days per week (P = .07). Adjusted for age and body mass index (calculated as weight in kilograms divided by height in meters squared), the odds ratio for death from ALS for participants with strenuous PA 3 or more days per week compared with no reported strenuous PA was 1.56 (95% CI, 1.02-2.37; P = .04).

Conclusions and Relevance  To our knowledge, this is the first cohort study to report an increased risk for ALS mortality associated with strenuous PA in postmenopausal women. The association between strenuous PA and ALS risk observed does not compromise the overall benefit of strenuous PA for total mortality, coronary heart disease, and breast cancer reported in other WHI investigations, but it may provide an important clue to the etiology of ALS, if replicated by other studies.

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Figure 1.
Age-Adjusted Hazard Ratios for Amyotrophic Lateral Sclerosis Mortality in Women With 3 or More Days per Week of Strenuous Physical Activity vs None at Baseline and Ages 50, 35, and 18 Years

Error bars indicate 95% confidence intervals.

aP < .05.

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Figure 2.
Age-Adjusted Amyotrophic Lateral Sclerosis (ALS) Mortality Rates for Women With 3 or More Days per Week of Strenuous Physical Activity (PA) vs None by Baseline Body Mass Index (BMI), Diabetes, and Smoking Status

PYs indicates person-years; error bars, 95% confidence intervals.

aP < .05 for difference in age-adjusted death rates.

bCalculated as weight in kilograms divided by height in meters squared.

cThere were only 3 deaths from ALS among women with diabetes, with no deaths from ALS among diabetic women who performed strenuous PA on 3 or more days per week; age-adjusted mortality rates and 95% confidence intervals could not be calculated by level of strenuous PA.

dSmoking status was defined as never (<100 cigarettes/lifetime), past (≥100 cigarettes/lifetime and no use within the past 6 months), or current (any use within the past 6 months).

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