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Decoding Prodromal Lewy Body Disease: Clinical Differences Between Isolated REM Sleep Behavior Disorder and Hyposmia
Luke Vikram Banerjee1, Jacopo Pasquini1,2, Robin Henderson3
1Clinical Ageing Research Unit, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
European Journal of Neurology
|August 6, 2026
Summary
Prodromal Lewy body diseases show distinct subtypes. Isolated REM Sleep Behavior Disorder (iRBD) presents a greater autonomic symptom burden, particularly constipation and urinary issues, compared to hyposmia with dopamine transporter deficit.
Area of Science:
- Neurology
- Neuroscience
- Clinical Medicine
Background:
- Lewy body diseases (LBDs) exhibit heterogeneity, apparent even in early stages.
- Prodromal heterogeneity may reflect distinct subtypes with varying clinical, imaging, and biomarker profiles.
- This study characterizes two key prodromal cohorts: isolated REM Sleep Behavior Disorder (iRBD) and hyposmia with dopamine transporter deficit.
Purpose of the Study:
- To provide a detailed clinical characterization of two enriched prodromal Lewy body disease cohorts.
- To compare clinical profiles of iRBD and hyposmia with dopamine transporter deficit against healthy controls.
- To identify specific symptom differences between prodromal LBD subtypes.
Main Methods:
- Cross-sectional study of 360 iRBD, 1101 hyposmia/dopamine transporter deficit, and 283 healthy controls (Parkinson's Progression Markers Initiative).
- Compared Montreal Cognitive Assessment (MoCA), SCOPA-AUT, and MDS-UPDRS Parts I-III using earliest available assessments.
- Utilized age/sex-adjusted permutation testing for group differences and descriptive analysis for item-level contributions.
Main Results:
- Both prodromal cohorts scored significantly worse than controls across all assessments.
- Isolated REM Sleep Behavior Disorder (iRBD) showed higher autonomic dysfunction (SCOPA-AUT) and non-motor symptom scores (MDS-UPDRS Part I) than hyposmia.
- Constipation and urinary symptoms were the primary drivers of increased symptom burden in iRBD.
Conclusions:
- Isolated REM Sleep Behavior Disorder (iRBD) is linked to a significantly higher autonomic symptom burden than hyposmia with dopamine transporter deficit in prodromal Lewy body disease.
- Urinary and constipation symptoms represent the most substantial differences between these prodromal subtypes.
- These findings support distinct clinical phenotypes within prodromal LBD, aiding subtype identification and management.
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