This is an application for a K23-Mentored Patient-Oriented Research Career Development Award entitled "Parkinson's disease, cognitive impairment, and structural MRI." The overall goal of the proposal is to investigate the neuroanatomical bases of Parkinson's disease dementia (PDD) and mild cognitive impairment (PD-MCI) using structural MRI methods coupled with clinical and neuropsychologicalevaluation. The proposed research and training in neuroimaging, cognitive neuroscience, Parkinson's disease (PD), and clinical research methods will provide the applicant with the necessary skills to become an independent investigator in these non-motor aspects of PD. 777/s proposal investigates in vivo neuroanatomical changes associated with PD cognitive dysfunction using volumetric MRI and whole brain voxel-based morphometry combined with neuropsychological assessment. PD subjects with dementia (PDD), amnestic PD-MCI, nonamnestic PD-MCI, cognitively normal PD (PD-NCI), and age-matched, healthy, cognitively normal controls (NCs) will be studied.
Aim 1 examines specific mesial temporal lobe structures including the hippocampus, entorhinal cortex, and parahippocampal white matter in the region of the perforant path across the PD cognitive spectrum. Since these mesial temporal lobe structures are involved in declarative memory and affected in early AD, atrophy in these regions in PD may represent dual AD pathology, especially in PDD and PD-MCI subjects with greater amnestic deficits on neuropsychological evaluation. However, since declarative memory is not the only cognitive domain affected in PD, Aim 2 investigates other neuroanatomical regions such as the frontal- striatal system that may be preferentially involved in executive or attentional dysfunction and affected in PDD and PD-MCI subjects with greater nonamnestic deficits. Thedifferent atrophy patterns detected on structural MRI in amnestic and nonamnestic types of PDDand PD-MCI may signify different underlying pathology and thus, have implications for future research on the progression of PD-MCI, development of biomarkers for incipient PDD, and design of treatment interventions. Cognitive impairment in PD is a clinically significant and frequent problem. It affects both patient and caregiver, and as a public health issue, impacts not only quality of life, but also morbidity and mortality. Dementia occurs in about 40%, and milder cognitive deficits are frequently present. The cognitive deficits present unique challenges for the physician and patient in achieving optimal control of PD motor symptoms. Our understanding of the neuroanatomical substrates of PD cognitive dysfunction, particularly compared to its well-known motor deficits, remains limited. This application will provide an informative, in vivo study of the neuroanatomical underpinnings of PD cognitive impairment.
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