Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Predicting Alpha-Synuclein Pathology Pre-Mortem

Parkinsonism Relat Disord; ePub 2018 May 17; Shprecher, et al

Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. However, probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments, such as the Mayo Sleep Questionnaire (MSQ), may provide a cost effective means of predicting LTS, according to a recent investigation. Since 2007, 602 subjects in the Arizona Study of Aging and Neurodegenerative Disorders had clinician assessment for PRBD (298 with, 304 without support of the MSQ), completed cognitive and movement examinations, and had neuropathological assessment. Mean age at death was 84.8 years. Investigators found:

  • Histological evidence of LTS was found in 80/101 (79.2%) cases with PRBD and 198/501 (39.5%) without PRBD.
  • Overall sensitivity for predicting LTS by PRBD diagnosis was 28.8%, specificity 93.5%, positive predictive value (PPV) 79.2%, negative predictive value (NPV) 60.5%.
  • Subjects with PRBD died an average of 4.5 years earlier than those without.
  • PRBD was not present in any of 46 subjects with incidental Lewy body disease.


Shprecher DR, Adler CH, Zhang N, et al. Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis. [Published online ahead of print May 17, 2018]. Parkinsonism Relat Disord. doi:10.1016/j.parkreldis.2018.05.020.

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