Objective/Rationale:
Patients with Parkinson’s disease (PD) are at increased risk to develop dementia compared with the general population. However, not all patients experience this symptom, and in those who do, the time to dementia varies substantially from patient to patient. Autopsy studies show increased accumulation of amyloid-beta in the brains of PD patients who developed dementia early during the course of their disease. Researchers have recently shown that abnormal amyloid-beta concentrations can be found in the cerebrospinal fluid (CSF) of a considerable proportion of patients with newly-diagnosed PD. In this project they will examine whether amyloid-beta and related CSF markers can aid in the early prediction of dementia in PD.
Project Description:
These researchers have obtained CSF at time of diagnosis in more than 100 patients with PD, have followed these patients for several years, and have measured CSF concentrations of different amyloid-beta forms and other proteins, such as tau. They will further measure a range of additional proteins that have been directly or indirectly linked to altered amyloid-beta processing, including markers of amyloid-beta production, of the brain’s immune defense (microglia), and of neuronal (synaptic) function. Using seven-year clinical follow-up data, they will then investigate if and how well these markers can predict cognitive decline and particularly the risk of and time to dementia in PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The main goal of this study is to identify CSF biomarkers that could aid in the early identification of patients with PD who are at risk to develop dementia. This would be valuable for clinical management, future trials of preventative agents, and early initiation of such treatments once they become available.
Anticipated Outcome:
Results from this study will be available within two years and will help to determine the utility of a panel of CSF biomarkers in the early prediction of dementia in patients with PD. If such prognostic biomarkers are identified and verified by other clinical studies, they could be used for more efficient recruitment to future clinical trials that test agents that have the potential to prevent or delay the development of dementia in PD.