Shared etiology of late- and adult-onset multiple sclerosis

Late-onset multiple sclerosis (LOMS), defined as disease onset at or after 50 years, is increasingly recognized and associated with distinct features. However, it remains unclear whether LOMS differs etiologically from adult-onset multiple sclerosis (AOMS).

To determine whether established MS risk factors differ between LOMS and AOMS and influence age at onset.

We conducted a Swedish population-based case-control study including 3950 incident MS cases and 7340 controls. Cases were classified as LOMS (n = 396) or AOMS (n = 3554). Associations between risk factors and LOMS and AOMS were estimated using logistic regression. Case-only analyses assessed associations with age at onset.

Most MS risk factors, including MS heredity, HLA-DRB1*15:01, Epstein-Barr nuclear antigen (EBNA)-1 antibody levels, smoking, and low sun exposure, were associated with both onset groups, with stronger effects in AOMS. Elevated body mass index at age 20 years was associated with AOMS, while estimates in LOMS were imprecise. Case-only analyses showed no association with disease timing. Exposure distribution varied across birth cohorts, suggesting cohort effects.

Established MS risk factors appear to be more clearly related to disease susceptibility than to timing of onset. The broadly consistent risk factor profiles support a shared etiology, although modest differences cannot be excluded.