The Generative Brain

Denouel A et al. 2023, The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality, an age-period-cohort analysis (Eur J Epidemiol 38:757-764)

A French national surveillance study that asks whether sporadic CJD, usually treated as a chance event in the brain, also shows the fingerprint of something in the environment. The Paris Brain Institute prion team and the AP-HP national CJD reference centre, with an epidemiologist from Inserm CESP at Villejuif, took 2,475 probable or definite sporadic CJD deaths at ages 45 to 89 recorded by the French surveillance network from 1992 to 2016 and fitted an age-period-cohort model. Mortality rose with each later birth cohort: against people born in 1937, those born in 1962 had about 1.65 times the risk and those born in 1922 about 0.60 times, a pattern the authors read as consistent with an environmental factor acting on susceptibility. They raise animal prions, including sheep scrapie and atypical BSE, diet changes and other exposures only as hypotheses, and call for replication elsewhere. Published online 16 May 2023, open access under CC BY. This entry is information only and says nothing about risk to any individual.

Key facts

  • Six authors: first and corresponding author Angeline Denouel, then Jean-Philippe Brandel, Danielle Seilhean, Jean-Louis Laplanche, Alexis Elbaz and Stephane Haik, with Elbaz and Haik sharing senior authorship; affiliations are the Paris Brain Institute (CNRS UMR 7225, Inserm U1127, Sorbonne University), the AP-HP national CJD reference centre at Pitie-Salpetriere, the Lariboisiere-Fernand Widal biochemistry department with Inserm UMR 1144, and Inserm U1018 CESP at Villejuif.
  • The paper is European Journal of Epidemiology 38(7):757-764, doi 10.1007/s10654-023-01004-5, PMID 37191829, PMC10276107; received 31 January 2023, accepted 6 April 2023, published online 16 May 2023, open access under CC BY 4.0.
  • Data came from the French national CJD surveillance network for January 1992 to December 2016: 2,510 probable or definite sporadic CJD deaths, of which 2,475 aged 45 to 89 were analysed (1,097 men and 1,378 women), after excluding 25 deaths under 45 and 10 at 90 or over; possible cases were not included.
  • Method: Poisson age-period-cohort regression with restricted cubic splines in Stata (apcfit), five year groups for age 45 to 89, period 1992 to 2016 and birth cohorts 1907 to 1967, with 1937 as the reference cohort, plus alternative parametrisations and a repeat in the M1 strain subgroup.
  • Overall sporadic CJD mortality was 4.58 per million person-years (95 percent CI 4.39 to 4.78); rates rose with age to a peak at 75 to 79 years and fell after that.
  • The period effect was steepest from 1992 to 1996 and the authors put it down mainly to surveillance getting better in the early years; standardised rates roughly doubled from 1992 to 1997 and then rose slowly.
  • The cohort effect was the main finding: relative to the 1937 cohort, the 1962 cohort had a 1.65 fold risk of dying of sporadic CJD (95 percent CI 1.19 to 2.27) and the 1922 cohort a 0.60 fold risk (0.51 to 0.69), described as a rather continuous rise across successive cohorts; the full age-period-cohort model fitted better than age-period (P 0.002) or age-cohort (P below 0.001) models.
  • Sex differed by age rather than overall: women had higher rates at younger ages (male to female ratio 0.44 at 45 to 49) and men at older ages (1.54 at 85 to 89), with no sex interaction with period or cohort; the age by sex term was not significant in the M1 only analysis, which the authors link to low power.
  • On causes, the authors stay at the level of hypothesis: they cite sheep scrapie transmission to human PrP mice and to a macaque, and atypical L-type BSE, as highlighting the possibility of a causal link in some cases, and mention rising consumption of animal products and mechanically separated meat, pesticides and antibiotics as candidate exposures that were not tested.
  • Stated limits: under 45s were excluded, non-M1 strains were too few to model, the M1 subgroup had less power, and the model is descriptive; the authors ask for replication in other countries, for studies of specific exposures, and for watching whether measures taken since the mad cow crisis change future sporadic CJD mortality.
  • Funding is recorded inconsistently: the article text says the work was supported by Sante publique France, while the Europe PMC grant field and the OpenAlex funder field both name the Institut de Veille Sanitaire.
  • Declared interests: Haik reports research support from Institut de Recherche Servier, LFB Biomedicaments and MedDay outside the study and patents on compounds to treat prion diseases; Elbaz reports grants outside the study; the other authors declare none.
  • Uptake as counted on 17 October 2026: Europe PMC lists 10 citing records and OpenAlex 9 citations with a field weighted citation impact of 0.67; citing works include a 2024 Nature Reviews Disease Primers overview of prion diseases and a 2025 China CDC Weekly survival study.
  • A companion paper from the same group, published in Eurosurveillance in December 2023, describes the same 1992 to 2016 French series: 25,676 notified suspects, 2,907 prion disease cases, of which 2,510 (86 percent) sporadic, with infectious forms declining and sporadic counts rising.
  • A June 2026 Research Square preprint from the same team, using 2,440 sporadic CJD cases from the same database and years, reports four significant spatial hotspots (South-East, Ile-de-France, Centre-South and Brittany) and different spatial patterns for the M1 and V2 strains, and again raises environmental risk factors; it is not peer reviewed.
  • The Sante publique France case table, updated 31 July 2026, shows yearly sporadic CJD deaths rising from 38 in 1992 to 161 in 2018, then 87 in 2024 and 87 in 2025, which extends past the study window but is not an analysis by cohort.

Timeline

  1. 1992Start of the surveillance window analysed.
  2. 2016End of the surveillance window analysed.
  3. 2023Manuscript received by the European Journal of Epidemiology.
  4. 2023Manuscript accepted.
  5. 2023Published online, open access under CC BY.
  6. 2023Companion 25 year French surveillance paper published in Eurosurveillance.
  7. 2026Same team posts a preprint on strain specific spatial clustering of French sporadic CJD for 1992 to 2016.
  8. 2026Sante publique France updates its yearly CJD case table.
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