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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-[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.

Affiliations

Han Soo Yoo  1 , Sangwon Lee  2 , Seok Jong Chung  1 , Yang Hyun Lee  1 , Phil Hyu Lee  1 , Young H Sohn  1 , Seungyeoun Lee  3 , Mijin Yun  2 , Byoung Seok Ye  1
1 Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
2 Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea.
3 Department of Mathematics and Statistics, Sejong University, Seoul, South Korea.