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Distribution of amyloid Beta and Its Influence on Neuropsychiatric Symptoms in Parkinson's Disease

Poster No:

236 

Submission Type:

Abstract Submission 

Authors:

Eunah Yang1, Yaeji Kim2, Hankyu Na3, Phil Hyu Lee3, Yong Jeong1

Institutions:

1Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of, 2Program of Brain and Cognitive Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea, Republic of, 3Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea, Republic of

First Author:

Eunah Yang  
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology
Daejeon, Korea, Republic of

Co-Author(s):

Yaeji Kim  
Program of Brain and Cognitive Engineering, Korea Advanced Institute of Science and Technology
Daejeon, Korea, Republic of
Hankyu Na  
Department of Neurology, Severance Hospital, Yonsei University College of Medicine
Seoul, Korea, Republic of
Phil Hyu Lee  
Department of Neurology, Severance Hospital, Yonsei University College of Medicine
Seoul, Korea, Republic of
Yong Jeong, MD., PhD.  
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology
Daejeon, Korea, Republic of

Introduction:

Parkinson's disease (PD) is traditionally categorized as a subcortical disorder originating from alpha-synuclein accumulation along the dopaminergic pathway, resulting in prominent motor symptoms. However, broadening this viewpoint, individuals with PD exhibit not only motor symptoms but also neuropsychiatric and cognitive symptoms. These non-motor manifestations suggest potential alterations in cortical involvement with subcortical connections. However, the correlation between the prevalence of these non-motor features and alpha-synuclein was found to be inconsistent. Consequently, this study adopts a novel approach by investigating the role of amyloid beta in the non-motor comorbidities of PD. This research aims to elucidate the amyloid burden associated with PD in relation to neuropsychiatric symptoms. Firstly, the study demonstrates the pattern of amyloid accumulation in PD patients using F-18 Florbetaben (FBB) PET imaging. This study also explores white matter microstructural changes in the amyloid-positive PD using diffusion tensor imaging (DTI).

Methods:

We acquired FBB PET and T1-weighted MR images from 137 idiopathic Parkinson's disease patients, categorized into 112 amyloid beta-negative and 25 amyloid beta-positive cases. Each patient underwent FBB PET, T1-weighted MR, and diffusion tensor imaging. Additionally, they went through cognitive assessments, including the Korean Mini-Mental State Examination (K-MMSE) and Seoul Neuropsychological Screening Battery (SNSB), while behavioral and psychiatric features were evaluated with the Neuropsychiatric Inventory (NPI) and Mild Behavioral Impairment (MBI) score.
Utilizing Desikan-Killiany-Tourville (DKT) cortical labeling and Freesurfer subcortical segmentation protocols, we assessed the regional standardized uptake value ratios (SUVr) across 62 cortical and 14 subcortical regions. Regions exhibiting distinct regional amyloid beta accumulation were selected based on age, sex, and disease duration-adjusted SUVr values and subsequently subjected to linear regression models with cognitive and neuropsychiatric measures. White matter deterministic tractography was conducted using MRTrix3 software. To depict differences in structural connectivity related to amyloid status, we employed threshold-free network-based statistics (TFNBS) to identify distinctive edges between the amyloid-positive and negative groups.

Results:

Widespread amyloid accumulation was observed across the entire brain, including the subcortex in amyloid-positive PD. The amyloid SUVr values revealed that the most significant association with amyloid was the burden of neuropsychiatric symptoms based on amyloid status but not with cognitive performance. Specifically, the amyloid accumulation was correlated with reduced motivation and affective dysregulation. When examining structural connectivity through DTI, amyloid-positive PD showed lower connectivity involving the anterior cingulate, temporal, and subcortical structures.
Supporting Image: figure1.JPG
Supporting Image: figure2.JPG
 

Conclusions:

In summary, this study highlights the explanatory role of amyloid beta in the manifestation of decreased motivation and affective dysregulation features in PD. The widespread distribution of amyloid throughout the brain, including the subcortex, emphasizes its extensive involvement in PD pathology. Moreover, observed structural connectivity differences, particularly in the anterior cingulate and other regions, emphasizing the complex neural implications of amyloid beta. These findings focus attention on the need for targeted therapeutic strategies addressing both motor and neuropsychiatric aspects in the comprehensive management of PD.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1

Modeling and Analysis Methods:

Connectivity (eg. functional, effective, structural) 2
Diffusion MRI Modeling and Analysis
PET Modeling and Analysis

Keywords:

Positron Emission Tomography (PET)
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Amyloid; Parkinson's Disease; Brain connectivity ; Neuropsychiatric disease

1|2Indicates the priority used for review

Provide references using author date format

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