Age at onset of amyotrophic lateral sclerosis is proportional to life expectancy

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with peak onset between 55 and 75 years and a life expectancy of three to five years (1). The incidence of ALS is relatively uniform across Europe, but may be lower in admixed populations (2). Clustering has been reported in Guam and on the Kii peninsula of Japan (3). Age of disease onset in ALS varies across populations and across historical cohorts. Familial ALS (FALS) is generally associated with a younger age of onset. This has been attributed to a higher genetic burden in susceptible people, causing earlier disease onset. A lower age of onset is reported in population isolates where incidence rates are high, and these lower rates of onset have also been attributed to the effects of a higher burden of genetic susceptibility (3). Data from the Irish ALS Register (unpublished) demonstrate that the age of onset of ALS appears to be increasing over time although the adjusted incidence rates and frequency of disease in the very old do not appear to have changed (4). We have tested the hypothesis that the mean age at onset of ALS is directly proportional to life expectancy in that region at the mid-point of the study period, and that this constant proportion accounts for all observed variations in age of onset seen in different geographical populations and between historical cohort studies.