Discordance Between Striatal Dopaminergic Imaging and Motor Performances in REM Sleep Behavior Disorder

Idiopathic REM sleep behavior disorder (iRBD) is a marker of early neurodegenerative synucleinopathy. Nigrostriatal dopaminergic dysfunction is often considered the primary pathological mechanism behind motor symptoms; however, other mechanisms have been proposed. The study aim was to identify whether there were iRBD patients with a discordance between motor testing and abnormal nigrostriatal uptake, and to characterise those patients.

This multicenter study included 108 subjects with polysomnography-confirmed iRBD who underwent [123I]-Ioflupane SPECT (DaT-SPECT) and quantitative motor testing within the same year. Participants were divided into 4 groups (motor slowing/DAT normal, motor normal/DAT positive, both normal, and both abnormal) and were investigated for differences in clinical characteristics. All participants were followed prospectively for a median of 2.5 years.

43/108 (40%) had discordance between DaT-SPECT and quantitative motor testing, with similar proportion of motor slowing/DAT normal and motor normal/DAT positive participants (n=20 and n=23 respectively). Motor slowing/DAT normal participants had worse MoCA scores (24.9 vs 26.4, p=0.022), a higher frequency of MCI (60% vs 22%, p=0.001), and more autonomic symptoms (SCOPA-AUT=18.7 vs 12.2, p=0.027) compared to the other groups. 3/20 (15%) of the motor slowing/DAT normal group phenoconverted (PD=2, DLB=1), at a median interval of 1.8 years.

This study revealed that motor alterations and abnormal nigrostriatal uptake are commonly discordant in iRBD, and that motor abnormalities are common even in those with normal DaT-SPECT. The presence of substantial cognitive and autonomic dysfunction in the motor slowing/DAT normal group suggests a different, likely more diffuse, progression pattern.