Diagnostic profiles of patients with late-onset Creutzfeldt–Jakob disease differ from those of younger Creutzfeldt–Jakob patients: a historical cohort study using data from the German National Reference Center

Abstract

In contrast to other neurodegenerative diseases, sporadic Creutzfeldt-Jakob disease (sCJD) is rarely diagnosed in patients older than 75 years. Data describing the characteristics of sCJD in the very old are rare and inconclusive. Therefore, a historical cohort study was designed to evaluate clinical, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) features of this group. Patients older than 75 years identified via the German surveillance program from 2001 to 2012 (n = 73) were compared to a random subsample of sCJD patients younger than 75 (n = 73) from the same time period using an historical cohort design. Older patients showed a faster disease progression represented by an earlier point of diagnosis and a shorter survival time (p < 0.001). In the early stages of disease, older patients presented slightly more often with dementia (p = 0.127) or dysarthria (p = 0.238), whereas disorders of the extrapyramidal (p = 0.056) and visual system (p = 0.015) were more common in the younger group. Atypical MRI profiles such as MRI lesions restricted to one hemisphere (p < 0.001) or cortical lesions only (p = 0.258) were found more frequently in patients older than 75 years, whereas typical cortical and basal ganglia hyperintensities were more common in the younger group (p = 0.001). We demonstrated for the first time that patients with late-onset sCJD differ from younger sCJD patients with respect to MRI profiles and initial clinical presentation, but not among CSF markers. Misclassification of Creutzfeldt-Jakob disease cases in patients older than 75 years seems likely due to atypical clinical and radiological presentation. This might contribute to lower sCJD incidence rates in this age group.