Age-period-cohort analysis of the incidence of multiple sclerosis over twenty years in Lorraine, France

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system. An increase in MS incidence over time is reported in several regions of the world. We aimed to describe the evolution of the annual MS incidence in the Lorraine region, France, from 1996 to 2015 and to analyze potential components of a possible change by a temporal effect of age at MS onset, MS onset period, and birth cohort, overall and for each sex. Cases were identified from ReLSEP, a population-based registry of MS cases living in Lorraine, northeastern France, with MS onset between 1996 and 2015. Age-period-cohort modeling was used to describe trends in MS incidence. Annual age- and sex-standardized incidences were relatively stable: 6.76/100 000 population (95%CI [5.76-7.91]) in 1996 and 6.78/100 000 (95%CI [5.72-7.97]) in 2015. The incidence ratio between women and men was 2.4. For all time periods, the peak incidence occurred between ages 25 and 35 years. Age-period-adjusted cohort and age-cohort-adjusted period analyses did not reveal a period or cohort effect. The incidence of MS remained stable over the study period in Lorraine, and we could not identify any particular effect of disease onset period or birth period on this evolution.

Figure 1

Change in overall annual sex- and age-standardized incidence of multiple sclerosis per 100,000 inhabitants in Lorraine from 1996 to 2015 (a), with 95% confidence intervals, and by sex standardized on age for women (b) and men (c), with 95% confidence intervals.

Figure 2

Time series of annual average incidence variation in multiple sclerosis per 100,000 population over age classes by period, all sexes combined (a), for men (b) and for women (c).

Figure 3

Time series of the change in annual average incidence for multiple sclerosis per 100,000 population during successive cohorts by period, all sexes combined (a), for men (b) and women (c).

Figure 4

Time series of annual average incidence variation in multiple sclerosis per 100,000 population next age by birth cohort, all sexes combined (a), for men (b) and for women (c).

Figure 5

Diagram of the age-period-cohort model and its sub-models. The models are nested from right to left. APC age-period-cohort model, AC age-cohort model, AP age-period model, Ad age-drift model, PC period-cohort model, Pd period-drift model, Cd cohort-drift model, A age model, P period model, C cohort model, A age model, t trend model, At age-trend model, Pt period-trend model, Ct cohort trend model, 1: intercept model. The term drift means that there must be some temporal variation in rates that cannot be interpreted as the effect of other non-specified parameters in the model.