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.
Bibliographical noteFunding Information:
This research was supported by a faculty research grant from Yonsei University College of Medicine (6-2018-0201), the National Research Foundation of Korea grant funded by the Korean government (NRF-2016R1C1B1015044), and the Brain Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (NRF-2018M3C7A1056898).
All Science Journal Classification (ASJC) codes
- Clinical Neurology