Temporal trends in motor neuron disease mortality in Spain (2000-2024): Population ageing versus generational risk factors.

OBJECTIVE: To analyse temporal trends in motor neuron disease (MND) mortality in Spain (2000-2024) and disentangle the independent contributions of age, period, and birth cohort effects. METHODS: A population-based ecological time-series analysis was conducted using nationwide mortality data. Age-standardised mortality rates (ASMR) were analysed using joinpoint regression (ages 0-85+). To isolate underlying drivers and mitigate random variability, age-period-cohort (A-P-C) modelling was applied to a targeted adult cohort (ages 25-84). RESULTS: A total of 23,663 MND deaths were recorded. Absolute annual deaths rose by 81.1% (682 in 2000 to 1235 in 2024). Men showed a steady upward ASMR trend (AAPC: 0.5%; 95% CI 0.3-0.7). Women showed an initial sharp increase (2000-2003; APC: 7.0%; 95% CI 0.7-19.1) followed by stabilisation (APC: 0.1%; 95% CI -1.3 to 0.5). The A-P-C model revealed strong cohort effects in both sexes, with an inverted U-shaped pattern peaking in the 1950-1955 cohorts, followed by marked declines. Period effects in men showed stability, whilst a moderate secular decline was observed in women. Local trends revealed declines in the younger cohorts and an increase in mortality risks limited to the older age groups (75-84 years). CONCLUSIONS: The rising absolute MND mortality burden in Spain is primarily driven by population ageing rather than a generalised increase in lifetime risk. Long-term trends are heavily shaped by generational birth-cohort dynamics, showing a notable risk reduction in more recent generations.