Imaging Studies of Cognitive Impairment in Parkinson s Disease

Background: \- Parkinson's disease causes slow movements, stiffness, and tremor. It can get worse over time, and in some cases can lead to dementia. Researchers are interested in how dementia affects the brain in people with Parkinson's disease. They will study both people with Parkinson s disease and healthy volunteers. They will give tests of thinking and memory, and look at brain activity using imaging studies. This may provide more information on what parts of the brain are not working well in people who have dementia related to Parkinson's disease. Objectives: \- To use imaging studies to see what parts of the brain do not work well in people with dementia caused by Parkinson's disease. Eligibility: * Individuals at least 40 years of age who have Parkinson s disease. * Healthy volunteers at least 40 years of age. Design: * Participants will be screened with a medical history and physical exam. * This study requires two outpatient visits over 2 days. * Participants will have tests of thinking, memory, and concentration. They will answer questions and fill out questionnaires. The tests will also look at how quickly they can move and handle small objects. The tests will take about 3 hours. * Participants will have magnetic resonance imaging to study the brain. Functional MRI (fMRI) can show what parts of the brain are used when performing a task. Participants will respond to images on a computer screen during fMRI. * Treatment will not be provided as part of this study.

Objectives: The purpose of this protocol is to identify the neural correlates of cognitive impairment in Parkinson disease (PD) using magnetic resonance imaging (MRI). Study Population: We will study 36 PD patients, defined by the UK Parkinson s Society Brain Bank diagnostic criteria \[1\], consisting of 12 patients with cognitively normal PD (PD-CogNL), 12 with PD with mild cognitive impairment (PD-MCI) \[2\], and 12 with PD with dementia (PDD) \[3\]. We will also study 12 age- and gender-matched healthy volunteers (HVs) as controls. Design: This is an observational study and includes 3 PD patient subgroups (PD-CogNL, PD-MCI and PDD) and HVs group. Eligible participants will have one visit lasting 2- 4 days, ideally over 2 consecutive days. If the visit cannot be completed within that time frame, a second visit may be scheduled within 3 months to complete the assessments. They will have a clinical assessment, cognitive assessment, and MRI scans. Outcome Measures and Hypothesis: The primary outcome measure is the Mini-Mental State Examination (MMSE) score and functional connectivity of cognitive networks, including default mode network, using restingstate functional MRI (fMRI). We hypothesize that there is a group difference in functional connectivity of cognitive networks between the PD patient subgroups and HVs. We also hypothesize that there is a correlation between the MMSE score and functional connectivity of the default mode network in PD patients. Secondary outcome measures are fractional anisotropy (FA) values, functional connectivity of the cognitive networks during working memory tasks, olfactory function score and the functional connectivity of olfactory network, and scales of brain perfusion and the functional connectivity of default mode network. We hypothesize that there: 1) is a group difference in FA values between PD patient subgroups and the HVs; 2) are group differences in functional connectivity of the cognitive networks during the working memory task between PD patient subgroups and HVs; 3) is a correlation between olfactory function and functional connectivity of the olfactory network in patients with PD-CogNL or PD-MCI; and 4\) are correlations between brain perfusion and the functional connectivity of the default mode network in PD patients.