REMPET2

Prodromal progression of [18F]FDG-PET-based Parkinson’s disease-related pattern expression in a cohort of iRBD patients as compared to baseline [123I]MIBG and [123I]FP-CIT-SPECT: a four-year prospective, multicentre, multimodal imaging, observational pilot study (REMPET2)

BACKGROUND
Isolated REM sleep behavior disorder (iRBD) is known to be prodromal for alpha-synucleinopathies like Parkinson’s disease (PD) and dementia with Lewy bodies. The [18F]FDG-PET-based PD-related brain pattern (PDRP) may be used to monitor disease progression and identify those who will phenoconvert. We longitudinally investigated the relationship between PDRP expression changes and motor, olfactory, cognitive, and imaging biomarkers in relation to phenoconversion risk in iRBD subjects.
METHODS
20 iRBD patients underwent two [18F]FDG-PET brain scans an average of 3·7 years apart. They also underwent baseline and repeated cognitive, motor, and olfactory testing, roughly corresponding to the times of the first and second PET scans. Additionally, 17 patients underwent baseline dopamine transporter imaging ([123I]FP-CIT-SPECT), and of these, 15 patients underwent cardiac adrenergic imaging ([123I]MIBG scintigraphy) at baseline and another two after the second [18F]FDG-PET scan.
FINDINGS
At baseline, 8/20 (40%) iRBD subjects expressed a PDRP z-score above the ROC-determined significance threshold of 1·98. At follow-up, 6 additional subjects exhibited suprathreshold PDRP z-scores, for a total of 14/20 (70%). PDRP expression increased in every subject between the two scans (p=0·00008). All subjects with pathological [123I]FP-CIT-SPECT scans at baseline, and all subjects except for one with abnormal [123I]MIBG scintigraphy at baseline, were found to have suprathreshold PDRP z-scores at follow-up. Additionally, four subjects (20%) have phenoconverted to clinical parkinsonism. Of these, three subjects underwent baseline [123I]MIBG and [123I]FP-CIT-SPECT imaging, all with abnormal results. Baseline and follow-up PDRP expression scores, as well PDRP score rate-of-change corresponded to changes in motor function and may signify imminent phenoconversion. This study is registered with the Netherlands Trial Register (NTR), number NL8057.
INTERPRETATION
Our results support the use of serial PDRP expression measurements as a prodromal PD progression biomarker in iRBD patients.
FUNDING
Stichting ParkinsonFonds Nederland and ParkinsonFonds Deutschland. W.H. Oertel is a Hertie Senior Research Professor (Charitable Hertie Foundation, Germany).