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Prodromal Lewy Body Disorder Features in REM Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy.

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Summary

Isolated rapid eye movement sleep behavior disorder (iRBD) with synucleinopathy presents with widespread clinical impairments before diagnosis. Early assessment is crucial for individuals with this prodromal synuclein disease.

Keywords:
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Area of Science:

  • Neuroscience
  • Neurology
  • Sleep Medicine

Background:

  • Isolated rapid eye movement sleep behavior disorder (iRBD) is a precursor to synucleinopathies like Parkinson's disease (PD) and dementia with Lewy bodies (DLB).
  • Biological heterogeneity in iRBD may affect disease progression and clinical presentation.
  • Understanding early clinical features in biomarker-defined synucleinopathy is crucial for timely intervention.

Purpose of the Study:

  • To investigate the clinical characteristics of individuals with iRBD and confirmed synucleinopathy.
  • To compare clinical and biological features between iRBD patients and healthy controls.
  • To identify early signs of neurodegeneration in prodromal synuclein disease.

Main Methods:

  • Utilized data from the Parkinson's Progression Markers Initiative (PPMI), a longitudinal, multi-center observational study.
  • Included polysomnogram (PSG)-confirmed iRBD participants positive for CSF α-synuclein seeds, without a PD or DLB diagnosis.
  • Assessed clinical features including mild cognitive impairment (MCI), subthreshold parkinsonism, and neuropsychiatric, autonomic, and sensory symptoms compared to healthy controls (HCs).

Main Results:

  • iRBD participants (N=197) showed significantly worse cognitive performance and higher odds of subthreshold parkinsonism, neuropsychiatric, autonomic, and sensory symptoms compared to HCs (N=136).
  • Common iRBD symptoms included hyposmia (75%), pain (54%), urinary issues (52%), constipation (49%), lightheadedness (40%), and anxiety (36%).
  • While few met criteria for prodromal DLB, most iRBD individuals exhibited multi-domain impairments, with abnormal dopamine transporter imaging linked to higher anxiety and antidepressant use.

Conclusions:

  • iRBD associated with synucleinopathy presents with multi-domain clinical impairment preceding formal diagnosis.
  • These findings underscore the importance of comprehensive clinical evaluation in early, biomarker-defined synuclein diseases.
  • Early detection of these diverse symptoms can aid in managing prodromal synucleinopathies.