Lee Taein, Jeong Yong
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Brain Behav. 2025 Sep;15(9):e70774. doi: 10.1002/brb3.70774.
Neuropsychiatric symptoms (NPS) in the Alzheimer's disease continuum affect the quality of life for patients and caregivers. Therefore, elucidating the mechanisms of NPS is needed to better understand NPS and enhance patient care. Several studies have investigated them using neuroimaging; however, none have considered the regional coexistence of amyloid-beta and tau pathologies and its association with functional networks. In this study, we aim to identify the neural correlates of NPS considering the molecular and functional levels of neural representation.
This study included data from amyloid-positive participants in the Alzheimer's Disease Neuroimaging Initiative database with positron emission tomography (PET), functional magnetic resonance imaging, NPS scores, and demographic data within one year and categorized them into groups with or without NPS factors. NPS were assessed using the neuropsychiatric inventory (NPI) and grouped into affective, apathy, hyperactivity, or psychosis factors. Amyloid-beta and tau accumulation measured by PET were compared between groups per region. Differences in functional connectivity of NPS- or NPS-type-specific pathologically altered regions were investigated using seed-to-voxel analysis. Further, a generalized linear model was constructed using the NPI score for each factor as the dependent variable, with functional connectivity strength, tau, and amyloid-beta accumulation as predictors.
Significant differences were observed in amyloid-beta and tau accumulation and functional connectivity between groups. The right middle temporal gyrus (rMTG) was associated with the affective factor, and the right parahippocampal and right fusiform gyri were associated with the apathy factor. Moreover, the generalized linear model was able to predict affective factor severity mainly based on the functional connectivity strength between the rMTG and the left supramarginal and angular gyri.
We identified the key regions specific to affective and apathy factors based on the areas with coexistence of amyloid-beta and tau pathologies and the accompanying altered functional connectivity.
阿尔茨海默病连续体中的神经精神症状（NPS）会影响患者及其照料者的生活质量。因此，需要阐明NPS的机制，以便更好地理解NPS并加强患者护理。多项研究已使用神经影像学对其进行了调查；然而，尚无研究考虑淀粉样蛋白-β和tau病理的区域共存及其与功能网络的关联。在本研究中，我们旨在从神经表征的分子和功能水平出发，确定NPS的神经关联。
本研究纳入了阿尔茨海默病神经影像学倡议数据库中一年内有正电子发射断层扫描（PET）、功能磁共振成像、NPS评分及人口统计学数据的淀粉样蛋白阳性参与者的数据，并将他们分为有或无NPS因素的组。使用神经精神科问卷（NPI）评估NPS，并将其分为情感、淡漠、多动或精神病因素组。对每组各区域通过PET测量的淀粉样蛋白-β和tau积累情况进行比较。使用种子点到体素分析研究NPS或NPS类型特异性病理改变区域的功能连接差异。此外，构建一个广义线性模型，将每个因素的NPI评分作为因变量，功能连接强度、tau和淀粉样蛋白-β积累作为预测因子。
两组在淀粉样蛋白-β和tau积累以及功能连接方面存在显著差异。右侧颞中回（rMTG）与情感因素相关，右侧海马旁回和右侧梭状回与淡漠因素相关。此外，广义线性模型能够主要基于rMTG与左侧缘上回和角回之间的功能连接强度来预测情感因素的严重程度。
我们基于淀粉样蛋白-β和tau病理共存区域以及伴随的功能连接改变，确定了情感和淡漠因素特有的关键区域。
