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Ann. Neurol., First published: 20 February 2020 | https://doi.org/10.1002/ana.25707 Dopaminergic depletion, β‐amyloid burden, and cognition in Lewy body disease

Han Soo Yoo, MD^a, Sangwon Lee, PhD^b, Seok Jong Chung, MD^a, Yang Hyun Lee, MD^a, Phil Hyu Lee, M.D., PhD^a, Young H. Sohn, MD, PhD^a, Seungyeoun Lee, PhD^c, Mijin Yun, MD, PhD^b,*, Byoung Seok Ye, MD, PhD^a,*

^aDepartment of Neurology, Yonsei University College of Medicine, Seoul, South Korea
^bDepartment of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea
^cDepartment of Mathematics and Statistics, Sejong University, Seoul, South Korea

^*Corresponding author

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 and 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 using18F‐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.

Key words: Subcortical shape; Lewy body disease, Parkinson’s disease, dementia with Lewy bodies, dopamine transporter, amyloid-β, positron emission tomography

논문정보

형식Research article
게재일2020년 02월 (BRIC 등록일 2020-03-03)
연구진국내 연구진
분야 의약학 > 응용의학

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