Introduction Sporadic Creutzfeldt-Jakob Disease (sCJD) is the commonest human prion disease, with a median age of onset of 68 years. We aimed to characterise the clinical, investigation, and neuropatho- logical features in young individuals with sCJD using data derived from national CJD surveillance.

Methods We interrogated the NCJDRSU database for individuals diagnosed with definite (post-mortem confirmed) or probable sCJD assessed from 2011-2021. We extracted data on clinical features, MRI, EEG, RT-QuIC, 14-3-3, and PRNP sequencing. Neuropathological findings were also studied where available. This data was compared in young individuals (≤50y) compared to all others.

Results 47 young individuals (4%) were identified (age at onset 25-50) from a total of 1178 cases. 14 (29.8%) were autopsy-confirmed. Psychiatric disturbance at presentation (36.2% vs 22%, p = 0.03) and longer disease duration (by 46 days, 95% CI 15-88, p < 0.01) were commoner in this group. CSF RT-QuIC showed lower sensitivity (81% vs 94%, p=0.01) in younger individuals. There was no difference in the sensi- tivity of MR brain, CSF 14-3-3, or EEG. There were no significant neuropathological differences in autopsy confirmed cases.

Conclusions Younger individuals with sCJD are more likely to present with neuropsychiatric symptoms, longer disease duration, and lower sensitivity of RT-QuIC.