Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder

Summary

This project will test the hypotheses that people with 5-HT RBD have systemic alpha- synuclein pathology, prodromal DLB signs, and brainstem lesions in regions that control REM sleep. AIM 1 will seek to detect abnormally phosphorylated alpha- synuclein aggregates on targeted skin biopsy in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD). Aim 2 will use ultra-high field MRI at 7T to examine the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures. Aim 3 will test for speech deficits. While these aims are independent we suspect that the severity of autonomic, speech and cognitive deficits will correlate with loss of neuromelanin signal on MRI and pathology on skin biopsy. The investigation is a longitudinal designed study to examine histopathology, neuroimaging changes and speech function from baseline (Time 1) to a follow-up after 30 months (Time 2). A total of 60 individuals, 30 with 5-HT RBD and 30 controls, will be recruited at Time 1, brought back at Time 2, and tested across all Aims at both study visits.

Eligibility

Age range

18–75 years

Sex

All

Healthy volunteers

Yes

Interventions

• Diagnostic Test
  Skin biopsy

  Skin biopsy to detect systemic alpha-synuclein pathology in 5-HT RBD

• Diagnostic Test
  Speech testing

  Speech Testing to quantify evolving signs of 5-HT RBD

• Diagnostic Test
  Ultra high field 7T MRI

  7T MRI to examine 5-HT RBD for evidence of brainstem neurodegeneration

Location