A Diagnostic Test for Dementia With Lewy Bodies

Study Overview
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Brief Summary
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The Syn-D Study will be evaluating α-synuclein in patients with suspected MCI-AD and MCI-DLB. Using a simple diagnostic test will improve clinical accuracy in diagnosing, earlier diagnosis, and distinguish between neurodegenerative diseases.

Detailed Description
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In collaboration with approximately 10 centers that specialize in DLB and dementia we will recruit a total of 80 individuals for the study: 40 subjects with suspected MCI-DLB and 40 with suspected MCI-AD will be recruited. All subjects will be enrolled into a 12 month longitudinal study where skin biopsies will be performed at 3 sites on each patients at 12 month intervals (baseline and 1 year). Detailed quantified examination, cognitive evaluation, history, and questionnaires will be performed at each visit and will be reviewed by a central panel of disease experts to confirm the diagnosis. Subjects enrolled in the study will have baseline evaluations and follow up visits at 12 months to define any changes to clinical diagnosis. Skin biopsies will be repeated at the 12 month follow up visit to determine the rate of P-SYN accumulation over time and rates of nerve fiber degeneration within punch skin biopsies.

Official Title
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A Diagnostic Test for Dementia With Lewy Bodies

Conditions
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MCI-AD, Early Stage Alzheimer's Disease, MCI-DLB, Early Stage Dementia With Lewy Bodies

Intervention / Treatment
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* Diagnostic Test: Syn-One Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 50 to 85 years of age Clinical diagnosis of mild cognitive impairment, and a presumed etiology of DLB or AD at enrollment Exclusion Criteria: Clinical evidence of severe peripheral vascular disease (Fazekas score of ≥ 3, or a large vessel stroke of ≥ 2 cm, history of ulceration, poor wound healing, vascular claudication) Clinically active coronary artery or cerebrovascular disease Current smoker or alcoholism History of allergic reaction to local anesthesia (for biopsy collection) Use of anticoagulants (aspirin or Plavix alone is allowed) Significantly impaired wound healing or history of scarring or keloid formation

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MCI-AD<br>Will be diagnosed using 'preclinical AD' criteria of mild cognitive impairment supported by a positive biomarker for AD. MCI defined as: 1. History of cognitive decline, noticed by either the patient, family member(s) or a medical practitioner but still independent in most complex daily activities. 2. Documentation of cognition not normal e.g., by MoCA or neuropsychological testing; 3. Does not meet the definition of dementia with MOCA <18 or global CDR 1 or greater (although exceptions may exist with appropriate justification). 4. Supportive AD biomarker (has positive biomarkers for both Aβ and neuronal injury using CSF or neuroimaging). | Diagnostic Test: Syn-One Test<br>* CND Life Sciences is expanding the utility of its diagnostic technology, the Syn-One Test, to pathologically distinguish between early DLB and Alzheimer's disease to prevent misdiagnoses and establish the relationship between progression and α-synuclein deposition by measuring α- synuclein accumulation in patient's nerve fibers using a simple skin punch biopsy.<br>|
| MCI-DLB<br>Will be diagnosed as prodromal probable MCI-DLB based on consensus criteria using 2 or more core clinical features of DLB (with or without the presence of biomarkers) or 1 or more core clinical features with 1 or more indicative biomarkers (reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET reduced Iodine-MIBG uptake on myocardial scintigraphy, PSG confirmation of REM without atonia). | Diagnostic Test: Syn-One Test<br>* CND Life Sciences is expanding the utility of its diagnostic technology, the Syn-One Test, to pathologically distinguish between early DLB and Alzheimer's disease to prevent misdiagnoses and establish the relationship between progression and α-synuclein deposition by measuring α- synuclein accumulation in patient's nerve fibers using a simple skin punch biopsy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This is a prospective longitudinal study of individuals with neurodegenerative DLB and AD disorders to improve the diagnostic precision and utility of the Syn-One TestTM. | To pathologically distinguish DLB from AD early in the course of the disease using the Syn-One TestTM, confirming disease diagnosis through prospective clinical assessments and follow up biopsy analyses over 12 months. | 2 years | 
| This is a prospective longitudinal study of individuals with neurodegenerative DLB and AD disorders to improve the diagnostic precision and utility of the Syn-One TestTM. | To define the rates of neuronal degeneration in DLB through systematic pathological quantitation of skin biopsies measuring P-SYN deposition and cutaneous nerve fiber degeneration, compared to AD, and correlating pathological findings with clinical assessments over the course of 12 months. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Aim 1 | The outcome measure will be an ordinal quantitation of P-SYN deposition within skin biopsies. The primary endpoint for is sensitivity and specificity of results in DLB and AD. We predict that a threshold of P-SYN >0 is a positive result and will separate DLB from AD using dichotomous measures, but ROC curve analysis will be performed to maximize sensitivity and specificity using continuous quantitative measurement of P- SYN. | 2 years | 
| Secondary Aim 2 | Will include P-SYN deposition, SGNFD, PMNFD and IENFD as continuous variables for statistical analysis. Data will be compared first using repeated measures Analysis of Covariance (ANCOVA), with DLB as the predictor variable. The primary dependent variable is the quantitative measure of P-SYN deposition. | 2 years |