Longitudinal Imaging Biomarkers of Disease Progression in DLB

The proposed project will enroll 90 subjects with probable DLB, 60 from Mayo Clinic Rochester (MCR) and 30 from Mayo Clinic Jacksonville (MCJ). Additionally, 45 controls will be enrolled, 30 from MCR and 15 from MCJ. We will obtain up to six assessments in each subject over the 5 years of the study, baseline, six month and annually thereafter. We will follow these cohorts with clinical and biospecimen data collection annually and once at six months, and CSF collection annually within the guidelines of the Parkinson's Disease Biomarker's Program (PDBP). Clinical neuroimaging will be performed annually and include: a) dopamine transporter imaging with Ioflupane (123I) SPECT (DaTscan) as the biomarker of LBD-related loss of dopaminergic activity, b) structural MRI AD- signature atrophy as the biomarker of AD-related neurodegeneration, c) β-amyloid (Aβ) deposition on PET as the biomarker of Aβ pathology. In patients from the MCR site, we will investigate AV-1451 PET. Since the specificity of AV-1451 PET is not established for tau deposition in DLB, we will investigate this biomarker in a subset of DLB patients to determine the pattern of AV-1451 uptake compared to clinically normal controls, and its association with atrophy, Aβ load and clinical disease progression in DLB.

Inclusion criteria

• Diagnosis of probable DLB, at least 18 years of age, reliable informant who personally speaks with or sees the participant at least weekly, sufficiently fluent in English, must be willing and able to consent to the protocol and undergo up to 6 visits over 5 years, willing and able to undergo neuropsychological testing and no contraindication to MRI imaging.

Exclusion criteria

• Presence of another neurologic disorder which could impact findings, such as multiple sclerosis, brain tumors, etc., unwilling to return for follow-up yearly and undergo neuropsychological testing and MR imaging, if undergoing Tau imaging cannot have QT Prolongation, do not have a reliable informant.