Structural signature of sporadic Creutzfeldt-Jakob disease

Eur J Neurol. 2019 Aug;26(8):1037-1043. doi: 10.1111/ene.13930. Epub 2019 Mar 25.


Background and purpose: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease caused by an abnormal isoform of the human prion protein. Structural magnetic resonance imaging in patients with pathologically confirmed sCJD was compared with cognitively normal individuals to identify a cortical thickness signature of sCJD.

Methods: This retrospective cross-sectional study compared patients with autopsy-confirmed sCJD with dementia (n = 11) with age- and sex-matched cognitively normal individuals (n = 22). We identified regions of interest (ROIs) in which cortical thickness was most affected by sCJD. Within patients with sCJD, the relationship between ROI cortical thickness and clinical measures (disease duration, cerebrospinal fluid tau and diffusion-weighted imaging abnormalities) was evaluated.

Results: Compared with cognitively normal individuals, patients with sCJD had significantly reduced cortical thickness in multiple ROIs, including the fusiform gyrus, precentral gyrus, precuneus and superior temporal gyrus bilaterally; the caudal middle frontal gyrus, superior frontal gyrus, postcentral gyrus, inferior temporal gyrus and transverse temporal gyrus in the left hemisphere; and the superior parietal lobule in the right hemisphere. Only one patient with sCJD had co-pathology consistent with Alzheimer's disease. Reduced cortical thickness did not correlate with disease duration, presence of diffusion restriction or elevated cerebrospinal fluid tau.

Conclusion: Cortical signature changes in sCJD may reflect brain changes not captured by standard clinical measures. This information may be used with clinical measures to inform the progression of sCJD and patterns of prion protein spread throughout the brain. These results may have implications for prediction of symptomatic progression and plausibly for development of therapeutic strategies.

Keywords: Creutzfeldt-Jakob disease; biomarker; cortical signature; cortical thickness; magnetic resonance imaging; neurodegenerative disorders; prion diseases; rapidly progressive dementia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / diagnostic imaging
  • Creutzfeldt-Jakob Syndrome / pathology*
  • Cross-Sectional Studies
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • tau Proteins / cerebrospinal fluid*


  • tau Proteins

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic