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Dopaminergic Depletion, β-Amyloid Burden, and Cognition in Lewy Body Disease

 Han Soo Yoo  ;  Sangwon Lee  ;  Seok Jong Chung  ;  Yang Hyun Lee  ;  Phil Hyu Lee  ;  Young H Sohn  ;  Seungyeoun Lee  ;  Mijin Yun  ;  Byoung Seok Ye 
 ANNALS OF NEUROLOGY, Vol.87(5) : 739-750, 2020-05 
Journal Title
Issue Date
Aged ; Amyloid beta-Peptides / metabolism* ; Brain / diagnostic imaging ; Brain / metabolism ; Brain / pathology ; Cognition / physiology ; Cognitive Dysfunction / etiology* ; Cross-Sectional Studies ; Dopamine Plasma Membrane Transport Proteins / metabolism* ; Female ; Humans ; Lewy Body Disease / complications ; Lewy Body Disease / metabolism* ; Lewy Body Disease / pathology* ; Male ; Positron-Emission Tomography
Objective: We aimed to determine the association between striatal dopaminergic depletion, cerebral β-amyloid deposition, and cognitive dysfunction in Lewy body disease (LBD). Methods: This cross-sectional study recruited 48 LBD patients (30 with dementia, 18 with mild cognitive impairment) and 15 control subjects from a university-based hospital. We measured the striatal dopamine transporter (DAT) activity and regional β-amyloid burden using N-(3-[18 F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) and 18 F-florbetaben (FBB) PET, respectively. The relationship between striatal FP-CIT uptake, regional cortical FBB uptake, and cognitive function scores was evaluated using path analyses. We also investigated the effects of striatal FP-CIT uptake and cortical FBB uptake on the interval between motor symptom and dementia onset. Results: Reduced striatal FP-CIT uptake was associated with increased FBB uptake in the posterior cortical regions, most prominently in the occipital cortices. Reduced FP-CIT uptake in the anterior putamen was associated with visuospatial dysfunction with mediation of increased occipital FBB uptake. Reduced FP-CIT uptake in the posterior putamen and an increased parietal FBB uptake were independently associated with memory dysfunction. Reduced striatal FP-CIT uptake was associated with attention, language, and frontal/executive dysfunction, independent of amyloid deposition. Increased FBB uptake, especially in the parietal cortex, was associated with earlier onset of dementia. Interpretation: Our results suggest that occipital β-amyloid deposition may contribute to the association between striatal dopaminergic depletion and visuospatial dysfunction in LBD patients. Although the effects of reduced DAT activity are more prominent than those of β-amyloid burden on cognitive dysfunction, the latter affects the onset of cognitive dysfunction.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Sohn, Young Ho(손영호) ORCID logo https://orcid.org/0000-0001-6533-2610
Ye, Byoung Seok(예병석) ORCID logo https://orcid.org/0000-0003-0187-8440
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Yang Hyun(이양현)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
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