Objective/Rationale:
By the time a person with Parkinson’s disease (PD) meets diagnostic criteria for dementia, the brain has already been ravaged. Unfortunately, current clinical, neuropsychological, and neuroimaging assessments cannot help diagnose or predict which PD patients will develop dementia. Moreover, there are several different pathologic findings at autopsy, including Alzheimer’s type pathology in one-third to one-half of PD patients with clinical dementia. The goal of this study is to develop a signature pattern of biomarkers that can identify the underlying pathologic cause of cognitive impairment and dementia in people with PD.
Project Description:
We will recruit 75 PD patients and 25 persons with no neurological or cognitive problems (i.e. controls). The 75 PD patients will either have no cognitive impairment, mild cognitive impairment or dementia. We will use a multimodal approach to develop a biomarker pattern associated with cognitive impairment in PD patients. Primarily we will use a state of the art imaging technique called resting state functional MRI (rs-fMRI) to determine which brain networks are associated with cognitive impairment. In addition, we will perform protein analysis from the cerebral spinal fluid, clinical quantitative analysis of motor control and comprehensive memory testing to fully characterize the biochemical and performance profile of each participant.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Therapies for PD cognitive impairment and dementia will be most effective when given before clinical symptoms are fully manifest. In addition, some PD patients with concomitant Alzheimer’s disease pathology might benefit from emerging therapies that target the specific molecular pathways associated with this disease. Therefore, biomarkers are urgently needed that are sensitive to preclinical cognitive impairment and sensitive to the underlying pathological etiology in PD dementia. This research aims to bridge this gap in knowledge.
Anticipated Outcome:
We expect to develop a neuroimaging signature of PD-associated cognitive dysfunction, which can be used as an objective biomarker for the degree of cognitive impairment in clinical trials. In addition, we expect to develop an in vivo technique to determine the frequency of AD-type pathology in PD patients with cognitive impairment, which would be applicable as a screening tool for clinical trials of molecularly-based cognitive therapies.