Dementia associated with PD (PDD) is common (affecting up to 80% of patients long-term) and highly disabling. Informative biomarkers are urgently needed to understand the pathology of PDD, to improve the early detection of cognitive deficits and to facilitate the development of treatments for PDD. Nuclear imaging technologies have the potential to produce such biomarkers. Numerous studies have used 11C-PIB to measure amyloid burden in Alzheimer's disease (AD) and other dementing illnesses. However, the experience with amyloid imaging in PD has been limited, in spite of post-mortem evidence for substantial amyloid deposition in patients with PD. One of the impediments to conducting additional studies with 11C-PIB has been the short half life of 11C (H20 min), necessitating an on-site cyclotron and in-house radiochemistry expertise. Since the PET isotope 18F has a 110 minute half life and a well established nationwide distribution network, it has been our long standing corporate goal to develop an 18F amyloid imaging agent for amyloid plaques. We have recently developed and validated in human trials such an agent, 18F-AV-45, which is easy to use, can be made cheaply and reliably, and can be distributed on a regional basis. Most importantly, the compound shows an excellent ability (as good as or better than 11C-PIB) to image amyloid plaques in Alzheimer's disease. In this STTR grant we propose to conduct the first ever clinical trial of 18F-AV-45 in PD patients. The over-arching aim of this study is to use 18F-AV-45 imaging of amyloid burden as a biomarker to test the relationship between amyloid burden and cognitive functioning in PD. We will image 25 PD subjects over 2 years with 18F-AV-45 and will compare imaging results with clinical data and CSF biomarkers (tau and a-beta) of amyloid pathology. We hypothesize that 18F-AV-45 binding will be associated with greater degrees of overall cognitive impairment, shorter interval between onset of motor and cognitive impairment, and pattern of CSF biomarkers reflecting amyloid pathology.
Successful validation of amyloid imaging as a biomarker for cognitive impairment in Parkinson's disease (PD) would represent a significant milestone in improving the diagnosis and treatment of this highly disabling feature of PD, and would represent a significant commercial opportunity for molecular imaging of these patients. However, little information is currently available regarding the amyloid burden, as measured by molecular imaging, in patients with PD or dementia associated with PD (PDD). 18F-AV- 45 is a fluorinated PET isotope that has favorable properties and has been shown to accurately identify amyloid pathology in Alzheimer's patients. In this project, we propose to use 18F-AV-45 to image amyloid pathology in patients with PD with cognitive impairment for the first time. Avid Radiopharmaceuticals is an experienced leader in developing new commercial PET tracers and is collaborating with world-experts on cognitive impairment in PD to conduct this clinical trial of amyloid imaging in PD and PDD.
| Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J et al. (2017) Regional brain amyloid-? accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia. PLoS One 12:e0177924 |
| Hoops, S; Nazem, S; Siderowf, A D et al. (2009) Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology 73:1738-45 |
