A leading Alzheimer’s disease researcher wants Australian recipients of human growth hormone procedures in the 1970s to undergo diagnostic testing for Alzheimer’s disease following recent confirmation of a link in UK patients.
Professor Colin Masters and colleague Professor Steve Collins, who lead the Australian National Creutzfeldt-Jakob Disease Registry at the Florey Institute of Neuroscience and Mental Health in Melbourne, warn the findings could pose a serious public health issue, with more than 2000 Australians potentially at risk.
The study published in Nature Medicine [link here] identified eight likely cases of young onset of Alzheimer’s disease from 1,848 recipients of cadaver-derived pituitary growth hormone (c-hGH) in the UK National Prion Monitoring Cohort.
The procedure has already been attributed to the cause of 80 cases of iatrogenic or medically-derived Creutzfeldt-Jakob disease (CJD) in the UK group.
The study authors said five of the eight c-hGH recipients were referred to the National Prion Clinic with symptoms consistent with early-onset dementia, with progressive cognitive impairment in two or more domains severe enough to affect the performance of daily activities and in some cases, progression was rapid.
Of the eight patients, an Alzheimer’s disease diagnosis had been made before clinic referral in three patients and two patients met diagnostic criteria for probable disease. While the remaining three patients either had mild cognitive impairment symptoms, had subjective cognitive symptoms or were asymptomatic.
The latency from c-hGH exposure to symptoms was three to four decades, and the ages of symptom onset ranged from 38-55 years old.
“The c-hGH recipients that we report here have developed new and progressive disturbances of cognition that meet standard definitions for dementia (five cases) or mild cognitive impairment (one case); they also show changes consistent with Alzheimer’s disease (definite in four cases; suggestive in two patients with a clinical diagnosis of dementia),” wrote the authors.
“Their relatively young age makes sporadic Alzheimer’s disease unlikely and, as inherited causes have been excluded, we considered that their symptoms and biomarker findings are a consequence of Aβ transmission from contaminated c-hGH received in childhood.
“Iatrogenic Aβ transmission has resulted in human disease on several occasions, with iatrogenic CAA now a recognised cause of early-onset stroke, and the individuals whom we describe in this report have received c-hGH batches that contain quantifiable Aβ and can be used to transmit Aβ experimentally in a new host.”
Professor Masters, who discovered the origin of the Aβ amyloid protein, said cadaver-derived hormones were used in Australia for short stature as well as fertility treatment. As a result, four women contracted and died from CJD in the 1980s, and 2,500 people are known to be at risk of CJD.
“We are now faced with a serious public health issue where large numbers of people may be at risk of developing early onset Alzheimer’s because of childhood exposures through Aβ-contaminated neurosurgical instruments and implants, or treatments with human cadaveric pituitary-derived hormones,” he said.
“Given the Nature Medicine article findings, we recommend screening anybody who received hormones derived from human pituitary glands for Alzheimer’s disease. Fortunately, it appears that blood tests are useful in detecting early onset Alzheimer’s disease.
“Testing this group would be cost-effective way of checking this at-risk population and determining the extent of risk.”