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The aim of this study was to quantify the improvements in case ascertainment which are considered to explain the rise in the incidence of sporadic Creutzfeldt-Jakob disease. The numbers of cases, falling into five 10-year age groups starting at the age of 30 and three calendar periods of report since 1970, were analyzed by Poisson regression, assuming a constant age distribution. The age-period and age-cohort models were applied and discussed. The age-period model showed that underreporting in 1970-1979 was greater among patients aged 70 years or older. The age-cohort model indicated that a cohort factor increased over the first half of the 20th century (e.g., the incidence in the generation born in 1940 was almost twice that in the generation born in 1920); this increase was probably an artifact due to the past underascertainment pattern. However, from a statistical viewpoint, both models lead to a good fit; the cohort factor may appear to be as relevant as the period factor in describing the trends in incidence. Thus, one can imagine an unlikely worst case scenario, assuming that an unknown cohort factor is involved. In that case, the age-cohort model gives more optimistic predictions than Neilson's model (BMJ 1996;312:1038-9). These results are consistent with both interpretations: The rise in incidence is governed by improvements in case ascertainment, and is greater among old people (the most accepted interpretation); this rise may depend on a cohort factor as well, which may correspond to the zoonotic hypothesis (a totally hypothetical interpretation). Interpreting the increase of sporadic Creutzfeldt-Jakob disease over generations in terms of exposure to putative environmental factors is still a matter of debate; ongoing epidemiologic surveys may provide more information. Presently, this increase can be explained as an artifact due to the past underreporting pattern, with 79% (95% confidence interval: 56, 90) of the cases among persons aged &gt; or =70 years being missed in 1970-1979.

Does Improvement in Case Ascertainment Explain the Increase in Sporadic Creutzfeldt-Jakob Disease Since 1970 in the United Kingdom?