Age-period-cohort effect on motor neuron disease mortality in the United States, 2001-2020

Motor neuron diseases (MND) are progressively fatal diseases causing loss of motor neurons throughout the body. Recent studies have suggested an increase in prevalence and mortality of amyotrophic lateral sclerosis (ALS), the most common adult-onset MND. It is unclear whether the increase is because of earlier diagnosis or potentially new exposures. Age-period-cohort (APC) analysis can help identify contributors to temporal disease trends by differentiating impacts of biological aging, historical time period, and birth cohort. The aim of this study is to evaluate APC effects on MND mortality in the United States from 2001 to 2020.

We analyzed deaths by MND for the period 2001-2020 in subjects aged 40-84 years. We used APC modeling to compute net drift, local drift, longitudinal age curve, rate ratios (RR), and confidence intervals (CI) for each period and cohort. Analysis used the APC Web Tool provided by the United States' National Cancer Institute.

Over the 20-year period, there were 119,890 MND deaths. Men consistently had higher mortality compared to women. Analysis yielded noteworthy birth cohort effects for men. For men, the cohort RR decreased from 1919 to 1953 and peaked again between 1959 and 1963. Men born after 1973 had a reduced RR = 0.77 (95% CI = 0.63-0.94). Women born after 1973 had a cohort RR = 1.00 (95% CI = 0.75-1.34).

APC analysis revealed potentially impactful age, period, and cohort effects in U.S. MND mortality between 2001 and 2020, with higher mortality among men and evidence of sex-specific cohort patterns. Cohort effects suggest potential generational differences in risk. Further investigation is needed to disentangle ascertainment effects from true etiologic influences.