Birth Cohort Effects in Neurological Diseases: Amyotrophic Lateral Sclerosis, Parkinson’s Disease and Multiple Sclerosis

Abstract

Background: Generational differences in disease rates are the main subject of age-period-cohort (APC) analysis, which is mostly applied in cancer and suicide research. This study applied APC analysis to selected neurological diseases: amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and multiple sclerosis (MS). Methods: The analyses were based on Swiss mortality data. Age-stratified data has been available for MS, PD and ALS since 1901, 1921, and 1942, respectively. APC analysis was performed within the framework of logit models. Main effect models were extended by implementing nested effects, i.e. age effects nested in subperiods, in order to account for the fact that age profiles may change for reasons other than generational influences. Results: In preliminary analyses, APC analysis yielded noteworthy birth cohort effects in all three diseases. After implementing nested effects, the birth cohort effects disappeared in ALS, and smoothed out in PD, where they were greater for the generations born before the 1920s. In MS, the birth cohort effects remained stable, and exhibited a peak in cohorts born in the 1910s and 1920s. Conclusions: APC analysis yielded some evidence for birth cohort effects, i.e. predisposing risk factors that may change in historical terms, in MS and PD, but probably not in ALS.

Age-period-cohort analysis of trends in amyotrophic lateral sclerosis incidence

“…Two previously published APC models for ALS incidence and mortality reported increased risk of death from ALS for those born between 1880 -1920 [11,12], while a third study concluded that there was no evidence of a birth cohort effect in ALS in Switzerland [10]. Our model shows no reportable period or cohort effects on incidence of ALS for those diagnosed in Ireland between 1996-2013.…”

“…The model showed that the increasing mortality rate was better explained by a cohort effect, than by time of death (period effect). A third analysis of mortality data from Switzerland between 1942 and 2008 applied a logit model to investigate APC effects in ALS mortality and concluded that there was no strong evidence of a birth cohort effect on ALS [10].…”

Characteristics and Prognosis of Oldest Old Subjects with Amyotrophic Lateral Sclerosis

“…A possible increase of ALS incidence, especially in oldest subjects [3,4,5,6], related to improved case ascertainment based on better diagnosis of the disease in old people [18] and near complete population coverage may contribute to the phenomenon. Also, changes in environmental exposure may be relevant [3].…”

“…Age-period-cohort analysis suggested a progressive increase with time period in the incidence of ALS, especially for the oldest age group [3,4,5,6]. Moreover, the proportion of extremely old ALS patients is expected to increase as occidental populations age [7].…”

Multiple Sclerosis and Amyotrophic Lateral Sclerosis: Finding and then Losing an Association

“…The same may be true, though to a lesser extent, for ALS. Age-period-cohort effects may also be at work, reflecting the effect of treatments, diagnostic patterns, competing mortality risk, and differences in the distribution of underlying risk factors [8]. Adequate registration of the diseases on death certificates and consistency of diagnosis will not overcome the effects of these other factors, which may obscure associations.…”