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

Research output: Contribution to journalArticle

Abstract

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-[18F]fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) and 18F-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. ANN NEUROL 2020;87:739–750.

Original languageEnglish
Pages (from-to)739-750
Number of pages12
JournalAnnals of Neurology
Volume87
Issue number5
DOIs
Publication statusPublished - 2020 May 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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    Yoo, H. S., Lee, S., Chung, S. J., Lee, Y. H., Lee, P. H., Sohn, Y. H., Lee, S., Yun, M., & Ye, B. S. (2020). Dopaminergic Depletion, β-Amyloid Burden, and Cognition in Lewy Body Disease. Annals of Neurology, 87(5), 739-750. https://doi.org/10.1002/ana.25707