Objective:

To assess whether duration and/or onset age of REM sleep behavior disorder (RBD) in isolated RBD (iRBD) patients affect the outcome of evolving into an overt synucleinopathy.

Background:

iRBD patients are known to be at high risk for developing an overt synucleinopathy [i.e., dementia with Lewy bodies (DLB) or Parkinson’s disease (PD)] and RBD often precedes years or decades before diagnosis of DLB or PD.

Design/Methods:

Participants with polysomnography-confirmed iRBD who have been followed prospectively for >4 years were included. 

Results:

Fifteen participants (45%) developed DLB (phenoconverters) and 18 participants (55%) remained as iRBD (stable iRBD). Follow-up years did not differ between phenoconverters and stable iRBD (6.2 ± 2.5 vs 6.3 ± 1.2 years; p=0.86). Time from baseline visit to DLB diagnosis was 4.0 ± 1.9 years and time from RBD onset to DLB diagnosis was 10.9 ± 5.4 years. At baseline, phenoconverters were older (69.4 ± 6.8 vs 63.7 ± 5.6 years old; p=0.013), had lower MMSE score (27.3 ± 1.5 vs 28.9 ± 1.3; p=0.002), and had more negative DaTQUANT putamen z-scores on 123I-FP-CIT SPECT (-1.71 ± 1.42 vs -0.28 ± 1.21; p=0.004). Sex (male; 87% vs 78%; p=0.51), education years (16.7 ± 2.5 vs 17.4 ± 2.4 years; p=0.38), APOE4 carrier (27% vs 35%; p=0.60), and UPDRS part III score (3.2 ± 3.2 vs 1.5 ± 2.1; p=0.073) did not differ between the two groups. Phenoconverters presented shorter RBD duration (6.9 ± 4.4 vs 16.3 ± 12.3 years; p=0.008) and older RBD onset (62.5 ± 8.3 vs 47.3 ± 14.9 years old; p=0.001).

Conclusions:

These findings suggest that iRBD patients with shorter duration and older onset of RBD are associated with an increased likelihood of progression into an overt synucleinopathy.