A longitudinal ¹⁸F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

Background: Pathogenic prion protein may start to deposit in some brain regions and cause functional alterations in the asymptomatic stage in Creutzfeldt–Jakob disease. The study aims to determine the trajectory of the brain metabolic changes for prion protein diseases at the preclinical stage. Methods: At baseline, we enrolled five asymptomatic PRNP G114V mutation carriers, six affected genetic PRNP E200K CJD patients and 23 normal controls. All participants completed clinical, diffusion-weighted imaging (DWI) and ¹⁸F fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG-PET) examinations. Longitudinal follow-up was completed in five asymptomatic mutation carriers. We set three-time points to identify the changing trajectory in the asymptomatic carriers group including baseline, 2-year and 4-year follow-up. Results: At baseline, DWI signals, the cerebral glucose standardized uptake value rate ratio (SUVR) and clinical status in 5 asymptomatic cases were normal. At the follow-up period, mild hypometabolism on PET images was found in asymptomatic carriers without any DWI abnormal signal. Further group quantitatively analysis showed hypometabolic brain regions in the asymptomatic genetic CJD group were in the insula, frontal, parietal, and temporal lobes in 4-year follow-up. The SUVR changing trajectories of all asymptomatic cases were within the range between the normal controls and affected patients. Notably, the SUVR of one asymptomatic individual whose baseline age was older showed a rapid decline at the last follow-up. Conclusions: Our study illustrates that the neurodegenerative process associated with genetic CJD may initiate before the clinical presentation of the disease.