Grant: Project Grant

Cognitive decline in Parkinson's Disease (PD) may occur, anywhere from 20-60%, with an impairment in one or more cognitive domains. Different subtypes of mild cognitive impairment (MCI) have been identified in PD. Single-domain non-amnestic impairments are most commonly frontal-executive in nature, while multi-domain impairments include any combination of deficits in various cognitive domains. Recent studies found that multi-domain MCI is highly associated with conversion to dementia. Today, the lack of information on the biological bases of these cognitive complications in PD has prevented the development of optimal treatments to alleviate these non-motor aspects. While the role of dopaminergic degeneration in cognitive dysfunction in PD may appear obvious, it has become clear that this alone cannot explain the severity of cognitive decline in those patients with multi-domain MCI and dementia. Other factors have to play an important role as well. In support of this, while there is large preclinical data suggesting a potential role of activated microglia, beta-amyloid and tau deposition in neurodegenerative processes, to date the in-vivo evidence of these pathologies in PD manifesting with multi-domain MCI and dementia remains unclear. This grant proposal shifts the focus from neurotransmitter changes to study the relationship between neuroinflammation, amyloid and tau deposition, using a set of new PET radiotracers. This data set will offer a unique multi-modal integrated approach to investigate and correlate clinical and pathophysiological mechanisms associated with more severe cognitive decline in PD.