Dementia With Lewy Bodies, Parkinson Disease, REM Sleep Behavior Disorder
Conditions
Brief 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.
Interventions
DIAGNOSTIC_TESTSkin biopsy
Skin biopsy to detect systemic alpha-synuclein pathology in 5-HT RBD
DIAGNOSTIC_TESTSpeech testing
Speech Testing to quantify evolving signs of 5-HT RBD
DIAGNOSTIC_TESTUltra high field 7T MRI
7T MRI to examine 5-HT RBD for evidence of brainstem neurodegeneration
Sponsors
University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Serotonergic REM sleep behavior (5-HT RBD) participants Inclusion Criteria: * Diagnosis of polysomnogram-confirmed RBD with history of dream enactment or clear dream enactment visualized on video from polysomnogram. * History of dream enactment began shortly after (less than 2 months) starting a serotonergic antidepressant medication. Control Participants Inclusion Criteria: * Age (±3 years) and sex matched to participants with 5-HT RBD * On serotonergic medication for at least 6 months without history of dream enactment. The following serotonergic medications will be included: Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline
Exclusion criteria
Serotonergic REM sleep behavior (5-HT RBD) participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monopitch as measured by fundamental frequency variability. | time point 1 (baseline) and time point 2 (24 months, +/- 3 months) | Participants' voice and speech quality will be examined for synucleinopathy syndrome. The focus on speech function is designed to detect subtle brainstem deficits prior to more overt manifestations of cortical dementia. |
| Phosphorylated alpha synuclein deposits on skin biopsy | time point 1 (baseline) and time point 2 (24 months, +/- 3 months) | Incidence (positive or negative) of phosphorylated alpha synuclein deposits. Indicating direct histopathological confirmation of underlying alpha-synuclein degeneration in 5-HT RBD in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD). |
| Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex | time point 1 (baseline) and time point 2 (24 months, +/- 3 months) | Examination of the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex. | time point 1 (baseline) and time point 2 (24 months, +/- 3 months) | Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex. |
| Speed of articulatory change as measured by F2 Transitions | time point 1 (baseline) and time point 2 (24 months, +/- 3 months) | Speed of articulatory change as measured by F2 Transitions, which are shown to be reduced in people with dysarthria |
Countries
United States
Contacts
Primary ContactJoy Schmidt
Outcome results
None listed