Anticipation of age at onset in multiple sclerosis: a Sardinian cohort study

BACKGROUND: To assess the temporal trend in multiple sclerosis (MS) onset during the last 50 years in Sardinia, Italy. METHODS: The authors used a cohort study to assess age at onset in 1,513 MS patients at the MS clinic in Cagliari, all born and living in Sardinia. They also assessed age at onset in 41 pairs of familial patients from two generations and 78 pairs of affected sibs. Each familial couple was paired with three couples of sporadic patients born in the same year as the familial ones. The time interval between the first symptoms and diagnosis was analyzed in first and second-diagnosed patients from both familial and control couples. RESULTS: Mean age at onset progressively decreased from the most remote to the most recent decade of birth (log-rank test 778.27, p < 0.0001), being 41 years in the former decade and 22 years in the latter. A genetic influence was ruled out, because the younger member of familial patients coming from two generations had onset 14.0 years earlier than the older one (p < 0.0001), as in the paired control couples (11.6 years, p < 0.0001). Moreover, mean onset in younger sibs was 3.4 years earlier than in older ones (p = 0.01), similar to that of control couples (4.1 years, p < 0.0001). CONCLUSION: Age at onset decreases progressively from older to younger generations in Sardinian MS patients. Nongenetic but recent widespread environmental changes might contribute to shortening of the preclinical phase-overt disease interval