Age-period-cohort analysis of trends in amyotrophic lateral sclerosis in Denmark, 1970-2009

Abstract

Amyotrophic lateral sclerosis (ALS) is a disease of the motor neuron with poorly understood etiology. Recent studies have suggested that the incidence rate of ALS and the rate of death from ALS are increasing, but it is unclear whether this is due to changing exposures or improvements in diagnosis. We used age-period-cohort models to investigate trends in ALS incidence (hospitalization) from 1982 to 2009 and ALS mortality from 1970 to 2009 in Denmark. Among those 45 years of age or older, 4,265 deaths (incidence rate = 5.35 per 100,000 person-years) and 3,228 incident diagnoses (incidence rate = 5.55 per 100,000 person-years) were recorded. Age-adjusted mortality rates increased by an average of 3.0% annually between 1970 and 2009 and by an average of 2.1% annually after 1982. Age-period-cohort analyses suggested that the full age-period-cohort model provided the best fit to the mortality data (P < 0.001), although restriction to the post-1982 period suggested that the age-cohort model provided the best fit. Age-adjusted incidence rates increased by 1.6% annually after 1982 (P < 0.001), which was best explained by the age-period model, with borderline significant cohort effects (P = 0.08). A consistent finding regardless of parameterization or data subset appeared to be an increase in ALS incidence and mortality rate with later birth cohorts, up to a birth year of at least 1910.

Keywords: age-period-cohort model; amyotrophic lateral sclerosis; brain disorders; neurodegenerative disorders; neuroepidemiology.

Figure 1.

Age-specific amyotrophic lateral sclerosis mortality rate in Denmark, 1970–2009.

Figure 2.

A) Amyotrophic lateral sclerosis mortality rate in Denmark, 1970–2009, stratified by age at time of death. B) Amyotrophic lateral sclerosis mortality rate by birth cohort, stratified by age at time of death. Lines correspond to each age group (solid: 45–50 years; short dash: 51–60 years; dotted: 61–70 years; dash-dot: 71–80 years; and long dash: >80 years).

Figure 3.

Age-period-cohort model of all deaths from amyotrophic lateral sclerosis in Denmark, 1970–2009, with average period effect constrained to be zero. A) Estimated period effects relative to 1990. B) Estimated birth cohort effects relative to 1920.

Figure 4.

A) Amyotrophic lateral sclerosis incidence rate in Denmark, 1982–2009, stratified by age at time of diagnosis (discharge). B) Amyotrophic lateral sclerosis incidence rate by birth cohort, stratified by age at time of diagnosis (discharge). Lines correspond to each age group (solid: 45–50 years; short dash: 51–60 years; dotted: 61–70 years; dash-dot: 71–80 years; and long dash: >80 years).

Figure 5.

Age-period-cohort model of amyotrophic lateral sclerosis incidence in Denmark, 1982–2009, with average period effect constrained to be zero. A) Estimated period effects relative to 1990. B) Estimated birth cohort effects relative to 1920.

Figure 6.

Relative amyotrophic lateral sclerosis mortality and incidence rates in women versus men in Denmark, 1970–2009.