REM Sleep Without Atonia Thresholds Linked to Cardiac Sympathetic Denervation but Not Striatal Dopamine Loss in Probable RBD

Quantitative thresholds for REM sleep without atonia (RWA) are widely used to support the diagnosis of REM sleep behavior disorder (RBD), a parasomnia that often precedes Parkinson disease and related synucleinopathies. But the optimal cutoff values and their relationship to the underlying neurodegenerative process have remained unclear, particularly across different populations. A new multicenter study from the University of Tsukuba and the Yoyogi Sleep Disorder Center in Tokyo, published in Sleep Medicine, provides the clearest link yet between RWA thresholds and a specific pathological feature: cardiac sympathetic denervation.

The study enrolled 91 Japanese patients with probable RBD (either isolated or associated with Parkinson disease). Each patient underwent video-polysomnography with quantitative RWA analysis, cardiac 123I-MIBG scintigraphy to assess sympathetic nerve integrity, and dopamine transporter imaging (123I-FP-CIT-SPECT) to measure striatal dopamine loss. The team applied three RWA quantification methods: the SINBAR criteria (submental plus flexor digitorum superficialis phasic activity), AASM tonic criteria (submental sustained activity), and AASM phasic criteria (FDS phasic bursts). Self-reported symptoms were also assessed using the RBD Questionnaire Japanese version (RBDQ-JP).

RWA thresholds differ from Western norms

The optimal diagnostic thresholds in this Japanese cohort were substantially lower than the Western standard of 27.2% for SINBAR criteria. The SINBAR threshold of 11.3% and the AASM phasic threshold of 9.4% both maximized sensitivity and specificity for identifying probable RBD in this population. This population difference likely reflects genetic and environmental factors influencing muscle activity during REM sleep and underscores the need for region-specific normative data.

RWA linked to cardiac sympathetic denervation, not striatal dopamine

The key finding was a strong association between RWA and cardiac sympathetic nerve damage. Among the 46 patients who met either the SINBAR or AASM phasic RWA threshold, 45 (97.8%) showed reduced cardiac MIBG uptake (heart-to-mediastinum ratio below 2.2), a well-established marker of cardiac sympathetic denervation.

In contrast, there was no significant correlation between the percentage of REM sleep without atonia and striatal dopamine transporter binding, nor with motor symptom severity as measured by the MDS-UPDRS-III. This dissociation suggests that RWA is more closely tied to the peripheral autonomic pathology of synucleinopathy than to the central dopaminergic degeneration that drives the motor features of Parkinson disease.

Self-report underestimates PSG-confirmed RWA

The study also found only a weak correlation between PSG-quantified RWA and the RBD Questionnaire Japanese version scores (r_s = 0.14-0.37). Notably, 19.7% of patients who exceeded the RWA threshold scored below the RBDQ-JP cutoff of 19.5, meaning their condition would have been missed by self-report alone. This reinforces the importance of objective PSG confirmation when RBD is suspected clinically.

Why it matters

These findings clarify the neurobiological substrate of RWA: elevated REM sleep without atonia reflects cardiac sympathetic denervation, a hallmark of peripheral alpha-synuclein deposition, rather than striatal dopamine loss. This dissociation is important because it suggests that RWA measured during routine PSG may serve as an early indicator of peripheral autonomic involvement in synucleinopathy, potentially before motor symptoms or significant dopamine loss emerge.

For clinical practice, the population-specific thresholds highlight the need for locally validated cutoff values rather than relying on Western norms. For research, the strong specificity of RWA for cardiac sympathetic denervation (97.8% of threshold-meeting patients had abnormal MIBG) positions PSG-quantified RWA as a cost-effective screening tool that could complement nuclear imaging in the workup of suspected RBD.

The weak correlation between self-report and PSG findings also carries a practical message: reliance on questionnaires alone misses roughly one in five patients who meet objective RWA criteria. As RBD gains recognition as an early prodromal marker for synucleinopathy, objective PSG confirmation becomes increasingly important for accurate diagnosis and for enrollment in neuroprotective trials.

The study is cross-sectional and cannot determine whether RWA precedes or follows sympathetic denervation. Longitudinal follow-up will be needed to establish whether RWA thresholds predict conversion to clinically defined synucleinopathy.

Bottom line

Quantitative RWA thresholds in Japanese patients with probable RBD are lower than Western norms and strongly predict cardiac sympathetic denervation but not striatal dopamine loss. PSG-confirmed RWA captures pathology that self-report questionnaires miss, supporting the role of objective sleep staging in the workup of suspected synucleinopathy.

Source: Mihashi I, Takei Y, Kawana F, Suzuki T, Fujimaki M, Hosaka T, Shioya A, Kokubo T, Yanagisawa M, Inoue Y, Saiki S. REM sleep without atonia thresholds are associated with reduced cardiac MIBG uptake but not with DAT-SPECT binding in probable REM sleep behavior disorder. Sleep Medicine. 2026 Jul 9;147:109132. DOI: 10.1016/j.sleep.2026.109132. PMID: 42442330.

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