Dopaminergic damage pattern predicts phenoconversion time in isolated rapid eye movement sleep behavior disorder

The exact phenoconversion time from isolated rapid eye movement (REM) sleep behavior disorder (iRBD) to synucleinopathies remains unpredictable. This study investigated whole-brain dopaminergic damage pattern (DDP) with disease progression and predicted phenoconversion time in individual patients.

Age-matched 33 iRBD patients and 20 healthy controls with ¹¹C-CFT-PET scans were enrolled. The patients were followed up 2-10 (6.7 ± 2.0) years. The phenoconversion year was defined as the base year, and every 2 years before conversion was defined as a stage. Support vector machine with leave-one-out cross-validation strategy was used to perform prediction.

Dopaminergic degeneration of iRBD was found to occur about 6 years before conversion and then abnormal brain regions gradually expanded. Using DDP, area under curve (AUC) was 0.879 (90% sensitivity and 88.3% specificity) for predicting conversion in 0-2 years, 0.807 (72.7% sensitivity and 83.3% specificity) in 2-4 years, 0.940 (100% sensitivity and 84.6% specificity) in 4-6 years, and 0.879 (100% sensitivity and 80.7% specificity) over 6 years. In individual patients, predicted stages correlated with whole-brain dopaminergic levels (r =  - 0.740, p < 0.001).

Our findings suggest that DDP could accurately predict phenoconversion time of individual iRBD patients, which may help to screen patients for early intervention.