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Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis.

David R Shprecher1, Charles H Adler2, Nan Zhang3

  • 1Cleo Roberts Center, Banner Sun Health Research Institute, Sun City, AZ, United States.

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|May 22, 2018
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Summary

Diagnosing Lewy type alpha-synucleinopathy (LTS) pre-mortem is challenging. Probable REM sleep behavior disorder (PRBD), identified with the Mayo Sleep Questionnaire (MSQ), shows promise in predicting LTS in neurodegenerative diseases.

Keywords:
Dementia with Lewy bodiesParkinson diseaseParkinson disease dementiaREM sleep behavior disorder

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Area of Science:

  • Neurology
  • Sleep Medicine
  • Pathology

Background:

  • Accurate pre-mortem diagnosis of Lewy type alpha-synucleinopathy (LTS) remains a significant clinical and research challenge.
  • Probable REM sleep behavior disorder (PRBD) may serve as a cost-effective predictive biomarker for LTS.
  • The Mayo Sleep Questionnaire (MSQ) can aid in the diagnosis of PRBD.

Purpose of the Study:

  • To investigate the utility of probable REM sleep behavior disorder (PRBD) diagnosis, supported by the Mayo Sleep Questionnaire (MSQ), in predicting Lewy type alpha-synucleinopathy (LTS) in a post-mortem study.
  • To assess the diagnostic performance (sensitivity, specificity, PPV, NPV) of PRBD in identifying LTS.

Main Methods:

  • Retrospective analysis of 602 subjects from the Arizona Study of Aging and Neurodegenerative Disorders with clinician assessment for PRBD, with or without MSQ support.
  • Neuropathological assessment for LTS was performed post-mortem.
  • Statistical analysis of PRBD prevalence in subjects with and without LTS, including various neurodegenerative conditions.

Main Results:

  • LTS was histologically confirmed in 79.2% of subjects with PRBD versus 39.5% without PRBD (p < 0.001).
  • PRBD demonstrated a specificity of 93.5% and a positive predictive value (PPV) of 79.2% for predicting LTS.
  • PRBD was significantly more prevalent in subjects with manifest neurodegenerative diseases associated with LTS (DLB, PD, PSP with LTS) compared to controls, Alzheimer's disease, or PSP without LTS.

Conclusions:

  • MSQ-supported PRBD diagnosis is a valuable tool for predicting LTS in patients with established neurodegenerative diseases.
  • PRBD diagnosis may not be as effective in predicting incidental Lewy body disease (ILBD).
  • Further research with polysomnogram-confirmed RBD subjects is needed to understand early pathological changes in the idiopathic stage of RBD.