Rhythm Disturbances in iRBD May Be Marker of Early Parkinson Disease

Valerie Cochen De Cock, MD, professor of sleep and neurology, Beau Soleil Clinic

Valérie Cochen De Cock, MD

In patients with idiopathic REM sleep behavior disorder (iRBD), impaired rhythm production and perception are correlated with early markers of Parkinson disease, suggesting that rhythmic skill-testing may have potential to be a short and inexpensive tool for screening in patients with iRBD.

The study results, collected and analyzed by Valérie Cochen De Cock, MD, professor of sleep and neurology, Beau Soleil Clinic, and colleagues, ultimately showed that those with iRBD (n = 21) with spontaneous tapping variability correlated with non&#8208;motor aspects of daily living (r = .57; P <.001), dysautonomia (r = .56; P <.01), olfaction deficits (r = .43; P = .04), and right caudate dopamine fixation ratio (r = .42; P <.05). Additionally, paced tapping variability correlated with odor discrimination (Pearson’s correlation coefficient, 0.53; P = .02).

For those with iRBD (threshold, 16.9% ±9.4) performed poorer than controls (n = 38; threshold, 12.3% ±7.3) in detecting rhythmic irregularity in a complex rhythm (P = .04). This anisochrony detection with music was not correlated with the typical early markers of Parkinson.

“There is consistent evidence that rhythm perception and production can be deteriorated in Parkinson probably as a result of the dysfunctional basal&#8208;ganglia&#8208;cortical circuitry characteristic of the disease,” Cochen De Cock and colleagues wrote. “Variability in rhythmic abilities in Parkinson can explain why, in most of the cases, compensation provided by an external rhythmic auditory cue can improve patients’ motor performance, such as gait.”

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These data suggest for the first time that degraded rhythmic abilities may mark the evolution of neurodegeneration in the basal&#8208;ganglia&#8208;cortical circuitry. The study authors noted that whether or not these rhythmic deficits manifest prior to cardinal motor symptoms of Parkinson may be worth investigation, with iRBD being a natural candidate in which to address the question. “[It leads] to synucleinopathies within 12 years in more than 70% of the cases,” they wrote.

When using a simpler rhythm (anisochrony detection with tones) there was no difference between those with iRBD (12.8% ±5.1) and the controls (12.3% ±5.0; P = 0.6) nor were there differences in discriminating simple durations (iRBD: 21.0% ±10.4; controls: 21.4% ±8.3; P = .3).

Those with Parkinson (n = 38) did not differ with controls on any of the perceptual tasks, including duration discrimination (24.7% ±11.8; P = .2) and anisochrony detection (tones: 13.4% ±6.1, P = .4; music: 12.5% ±6.5, P = .4).

Cochen De Cock and colleagues noted that rhythm production was tested in 2 conditions in order to examine the ability to generate a spontaneous endogenous rhythm, tapping rate, and variability in a finger-tapping task without external stimulation; and the ability to synchronize to an external rhythm with finger tapping to external auditory cues. Rhythm perception was measured with a task in which the participants had to detect a deviation from a regular rhythm.

In total, 55% of the iRBD group complained of olfaction dysfunction, a significantly larger proportion than that of the control group (21%; P = .03), but significantly lower than those with Parkinson (100%; P = .001). Olfaction threshold (iRBD: 3.2 ±2.1; controls: 7.4 ±1.7; P <.0001), discrimination (iRBD: 8.6 ±3.2; controls: 11.4 ±2.0; P = .001), identification (iRBD: 7.6 ±3.2; controls: 13.1 ±1.6; P <.0001), and sum scores (iRBD: 19.4 ±7.1; controls: 31.9 ±3.4; P <.0001)

were lower in participants with iRBD. Those with Parkinson had similar scores (respectively in the same order, 3.7 ±1.5; 7.8 ±3.4; 6.8 ±3.6; and 18.2 ±7.0; P >.4 for all).

Additionally, moderate and severe hyposmia and anosmia were present in 75% of the participants with iRBD and PD but not in the control group (P = .0001) who all had normosmia or mild hyposmia. The sensitivity of olfaction dysfunction (moderate, severe, or anosmia) to be associated with iRBD was 75%, and specificity was 100%.

“Prospective follow&#8208;up of these dysfunctions could also allow a better understanding of the networks that support them and how they adapt as neurodegeneration goes on,” Cochen De Cock and colleagues concluded. “Finally, this intriguing finding of rhythm disturbances in iRBD could be a new abnormal biomarker that could complete the cluster of other markers actually utilized to predict imminent phenoconversion to overt PD, or other synucleinopathies, within 3 or 4 years, and then to realistically test promising neuroprotective agents.”

REFERENCES

Cochen de Cock V, de Verbizier D, Picot MC, et al. Rhythm disturbances as a potential early marker of Parkinson’s disease in idiopathic REM sleep behavior disorder. Ann Clin Trans Neurol. Published online February 14, 2020. doi: 10.1002/acn3.50982