Pardis Zarifkar1, Jeehyun Kim2, Christian La3, Kai Zhang4, Sophie YorkWilliams5, Taylor F Levine6, Lu Tian7, Per Borghammer8, Kathleen L Poston9. 1. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA; Department of Nuclear Medicine and PET, Aarhus University Hospital, Denmark. Electronic address: pardis.zarifkar@regionh.dk. 2. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address: jehn92@gmail.com. 3. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address: christian.la013@gmail.com. 4. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address: kyezhang@gmail.com. 5. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA; Department of Psychology and Neuroscience, University of Colorado, Boulder, CO, 80309, USA. Electronic address: sophie.yorkwilliams@gmail.com. 6. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA; Department of Psychological & Brain Sciences, Washington University, 1 Brookings Drive, St. Louis, MO, 63130, USA. Electronic address: trhendershott@wustl.edu. 7. Department of Biomedical Data Science, Stanford University School of Medicine, 150 Governor's Lane, Stanford, CA, 94305, USA. Electronic address: lutian@stanford.edu. 8. Department of Nuclear Medicine and PET, Aarhus University Hospital, Denmark. Electronic address: borghammer@clin.au.dk. 9. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA; Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA, 94305, USA. Electronic address: klposton@stanford.edu.
Abstract
INTRODUCTION: To identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis. METHODS: In this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments. RESULTS: LHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment. CONCLUSION: We used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.
INTRODUCTION: To identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis. METHODS: In this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments. RESULTS: LHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment. CONCLUSION: We used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.
Authors: N Tzourio-Mazoyer; B Landeau; D Papathanassiou; F Crivello; O Etard; N Delcroix; B Mazoyer; M Joliot Journal: Neuroimage Date: 2002-01 Impact factor: 6.556
Authors: Taylor R Hendershott; Delphine Zhu; Seoni Llanes; Cyrus P Zabetian; Joseph Quinn; Karen L Edwards; James B Leverenz; Thomas Montine; Brenna Cholerton; Kathleen L Poston Journal: Mov Disord Date: 2018-12-10 Impact factor: 10.338
Authors: Bernard Ng; Gael Varoquaux; Jean Baptiste Poline; Bertrand Thirion; Michael D Greicius; Kathleen L Poston Journal: Neuroimage Clin Date: 2017-09-06 Impact factor: 4.881