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 neuropsychological evaluation. 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. This 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 frontalstriatal system that may be preferentially involved in executive or attentional dysfunction and affected in PDD and PD-MCI subjects with greater non-amnestic deficits. The different atrophy patterns detected on structural MRI in amnestic and non- amnestic types of PDD and 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.
| Mata, Ignacio F; Leverenz, James B; Weintraub, Daniel et al. (2016) GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease. Mov Disord 31:95-102 |
| Davis, Marie Y; Johnson, Catherine O; Leverenz, James B et al. (2016) Association of GBA Mutations and the E326K Polymorphism With Motor and Cognitive Progression in Parkinson Disease. JAMA Neurol 73:1217-1224 |
| Srivatsal, Sindhu; Cholerton, Brenna; Leverenz, James B et al. (2015) Cognitive profile of LRRK2-related Parkinson's disease. Mov Disord 30:728-33 |
| Goldman, Jennifer G; Holden, Samantha; Ouyang, Bichun et al. (2015) Diagnosing PD-MCI by MDS Task Force criteria: how many and which neuropsychological tests? Mov Disord 30:402-6 |
| Geurtsen, Gert J; Hoogland, Jeroen; Goldman, Jennifer G et al. (2014) Parkinson's disease mild cognitive impairment: application and validation of the criteria. J Parkinsons Dis 4:131-7 |
| Goldman, Jennifer G; Williams-Gray, Caroline; Barker, Roger A et al. (2014) The spectrum of cognitive impairment in Lewy body diseases. Mov Disord 29:608-21 |
| Goldman, Jennifer G; Stebbins, Glenn T; Dinh, Vy et al. (2014) Visuoperceptive region atrophy independent of cognitive status in patients with Parkinson's disease with hallucinations. Brain 137:849-59 |
| Goldman, Jennifer G; Postuma, Ron (2014) Premotor and nonmotor features of Parkinson's disease. Curr Opin Neurol 27:434-41 |
| Goldman, Jennifer G; Stebbins, Glenn T; Leung, Vania et al. (2014) Relationships among cognitive impairment, sleep, and fatigue in Parkinson's disease using the MDS-UPDRS. Parkinsonism Relat Disord 20:1135-9 |
| Goldman, Jennifer G; Holden, Samantha (2014) Treatment of psychosis and dementia in Parkinson's disease. Curr Treat Options Neurol 16:281 |
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