Status: Enrolling by invitation
Keywords: Parkinson's Disease , REM Sleep Behavior Disorder , Dream enactment , Neurodegenerative Disease , Dementia with Lewy bodies , RBD
IRB Number: 00045164
Specialty: Neurology, Neurology, Neurology, Neurology, Neurology
Sub Specialties: Dementia, Movement Disorders, Parkinson's Disease, Sleep Disorders, Neurodegenerative Disorders
Study Design and Purpose:
For unclear reasons, the rate of Parkinson disease (PD) in Utah is 30% higher than the national average. 1 As rate of Alzheimer disease is actually 10% lower than national average, longevity is not an adequate explanation for this finding. 80% of PD patients will eventually develop dementia. Dementia with Lewy bodies (DLB) and PD dementia, collectively known as Lewy body dementia (LBD), are the second leading cause of age-associated neurodegenerative dementia. 2,3 With a growing geriatric population, there is an urgent need to develop early detection and prevention strategies for LBD. This protocol is designed to clarify prevalence of risk factors for LBD, determine which risk factors and biomarkers are associated with diagnosis of LBD over time, and establish a cohort at-risk for LBD to allow rapid recruitment into future neuroprotection trials.
It has three components:
- Survey study- to obtain a representative sample of the local geriatric population.
- Cohort- enrolling a subset of at-risk and control participants (recruited primarily from the survey.)
- Biorepository- enrolling cohort and affected PD/atypical parkinsonism subjects.
- Determine the proportion of the Utah population aged 50 and over with iRBD and other risk factors (anosmia, constipation, mild cognitive impairment (MCI), psychosis, environmental exposures, family history) for LBD. This will be done using a survey in our geriatrics and primary care clinics.
- Determine relationship between history of sleep walking, as well as putative LBD risk factors, for presence of iRBD.
- Establish a cohort of “at risk” and control participants in a prospective study of LBD risk (with annual cognitive, motor, olfactory, color vision assessments). “At risk” will include those with iRBD, two or more first degree relatives affected, MCI, psychosis, anosmia, impaired color vision, or constipation.
- Measure baseline and annual symptom severity using the Hong Kong RBD self-report, 20 and explore relationship with risk of neurodegenerative disease, in our at-risk cohort.
- Determine how clinical characteristics of our cohort change over time. Baseline and annual assessments will include neurological exam (focused on possible motor symptoms of a parkinsonian disorder), neuropsychological assessment, olfactory and color vision testing.
- Determine rates of neurodegenerative disease in our cohort over time. This will be done using standard clinical criteria for diagnosis of dementing and parkinsonian disorders at each annual follow up exam.
- Determine contribution of baseline clinical characteristics to risk of neurodegenerative disease diagnosis.
- Create a biological sample bank containing “at risk”, control, and related neurodegenerative disease (PD, atypical parkinsonism) subject samples compatible with specific hypothesis generating (gene expression, metabolomic profiling, proteomic) and genetic techniques. Samples will be collected at each annual visit from cohort participants, but only once from subjects enrolled with a diagnosis of manifest parkinsonian disorder.
- Measure saliva alpha synuclein levels in all participants (where feasible), and annually in our cohort study participants. Hypotheses: 1) saliva alpha-synuclein levels will be elevated in subjects with alpha-synucleinopathy (PD, DLB, MSA) relative to controls or other disorders; 2) saliva alpha-synuclein level will correlate with imminent risk of alpha-synucleinopathy in the cohort study.
- Measure metabolomic profile of iRBD, newly diagnosed (untreated) PD, treated PD, diagnosed atypical parkinsonism, and control subjects. This will be done using peripheral blood as the tissue source. Hypotheses: 1) Analysis of metabolomic profiles will show clear differentiation between iRBD and control groups; 2) metabolomic profiles connoting risk of RBD will show overlap with those of manifest early (de novo) PD, treated PD, and or DLB; 3) metabolites related to cellular respiration will be linked to risk of neurodegenerative disease in iRBD subjects.
- Measure gene expression profile of iRBD, newly diagnosed (untreated) PD, treated PD, diagnosed atypical parkinsonism, and control subjects. This will be done using peripheral blood as the tissue source.
Hypotheses: 1) Analysis of gene expression profiles will show clear differentiation between iRBD and control groups; 2) gene expression profiles connoting risk of RBD will show overlap with those of manifest early (de novo) PD, treated PD, and/or DLB.
12. Measure impact of initial Parkinson disease medication therapy on selected biomarkers (metabolomics, gene expression). This will be done by measuring biomarker profiles before, and 6 weeks after, PD subjects starting first antiparkinsonian drug.
Principal Investigator: David Shprecher