Abstract Details

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years. Age-specific incidence declines after 80 years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations, and improving ascertainment for public health purposes.

To phenotype the clinical features and investigation profile of sCJD in adults over 80 years.

We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011-2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared.

10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3 months; p<0.001). Pyramidal signs (48.3% vs 34.2%; p=0.008) and akinetic mutism (55.1% vs 33.2%; p<0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; p=0.01) and cerebellar signs (65.4% vs 78.6%, p=0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of CSF RT-QuIC (92.9% vs 91.9%, p=0.74) was comparable, EEG was superior (41.5% vs 25.4%; p=0.006), and MRI was inferior (67.8% vs 91.4%; p<0.001).

Late-onset sCJD has distinct clinical features, shorter survival, and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain, and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive.