The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.

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We have analysed the familial occurrence of Creutzfeldt-Jakob disease (CJD) in 27 families selected from a total of 73 families. Fifteen per cent of all cases of CJD have a family history of disease consistent with autosomal dominant transmission. The onset of disease in familial cases is significantly earlier than in sporadic cases. A maternal effect was not found, nor was there evidence for prenatal vertical transmission of the virus. Temporal and spatial separations between affected members demonstrates that incubation periods ranging at least from one to four decades are to be expected. Affected siblings tend to die at the same age, and not at the same time, which is consistent with some form of vertical transmission (either prenatal or early postnatal), assuming rather uniform incubation periods. CJD occurred in four families in members related by marriage, evidence in favour of horizontal or common source transmission in occasional cases. The familial occurrence of CJD and Alzheimer's disease (AD) were compared using data on 52 families with AD. The age at death and duration of disease in familial AD is greater than in familial CJD. Familial AD also occurs in a pattern of autosomal dominant transmission, without maternal effect. There were four families with AD in which one or more members died from CJD. There were an additional 17 families with AD in which one or more members presented with clinical features resembling CJD. Although virus causing an experimental spongiform encephalopathy was isolated from the brain of two cases of familial AD, most cases of sporadic and familial AD tested failed to cause disease when brain tissue was inoculated into nonhuman primates. The precise mechanism of spread of the virus in familial CJD remains unknown. The results of the present study are consistent with the hypothesis of a genetically inherited susceptibility to infection which is acquired in early infancy or childhood. Other proposed mechanisms such as prenatal vertical transmission or a common environmental source of infection seem less likely.