Synucleinopathies are now recognized as major causes of dementia. The principal synucleinopathies are the overlapping clinical entities of Parkinson disease (PD), including Parkinson disease with dementia (PDD), and dementia with Lewy bodies (DLB). PDD and DLB are the most common causes of dementia after Alzheimer disease (AD). A clinical distinction between PDD and DLB, and distinguishing them from AD, is often difficult and, perhaps more importantly, the clinician encounters many situations in which it is unclear from clinical data and structural imaging whether a dementia reflects predominantly a single process or a complex one with Alzheimer changes coexisting with one or more of the other pathologies. In addition, as more specific therapies become available, it will be important to have methods to distinguish among the contributing pathological processes. The intent of this project is to use amyloid PET (PIB PET) combined with Clinical and neuropsychological evaluation, fluorodeoxyglucose (FDG) PET and dopamine transporter PET (in DLB ) to determine the contribution of amyloid deposition to dementia in PD and DLB.
The specific aims are as follows: 1) to perform PIB PET in DLB and PDD subjects that have been carefully characterized with respect to clinical features, changes on structural MRI, PD rating scales, neuropsychological performance, FDG PET and DAT PET (DLB);2) to perform PIB PET at study entry and after 3 years in PD subjects characterized at both time points with respect to clinical features, PD rating scales, changes on structural MRI, neuropsychological performance and FDG PET. The overall objectives of the project are to determine the following: 1) the contribution of beta-amyloid accumulation to the dementia in PDD and DLB;2) the role of beta-amyloid accumulation in the conversion of PD to PDD;3) the contribution of FDG, PIB PET and dopamine transporter PET, correlated with clinical evaluation, neuropsychological testing and structural imaging, to understanding the pathophysiology of dementia associated with synucleinopathies.
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