摘要：去脂蛋白E e4 (APOE e4)基因為阿茲海默氏症之危險因子。APOE e4基因已被指出與一般健康受試者之腦部灰質和認知功能改變有關，特別是與記憶及執行功能的改變有密切關連。此外，文獻亦指出 APOE e4與腦部白質的發展與修復有密切關聯。然而，多數既有文獻僅著墨於老年族群的APOE e4基因與認知及灰質功能改變的研究，對白質的討論也甚少。因此，本計劃希望透過為期三年的研究，針對老中青三族群的健康受試者，探討APOE e4基因對受試者之認知功能與腦白質、灰質之構造完整性(integrity)的影響。本研究利用由理論延伸與阿茲海默氏症病理相扣的認知功能測量工具，來研究受試者之認知功能。此外，我們亦納入最先進的「擴散頻譜造影技術 (Diffusion Spectrum Imaging) 」以及「影像資料分析技術 (FreeSurfer) 」來了解受試者腦白質與灰質的完整性，並與記憶及執行功能之實驗結果做整合分析。本研究成果將會對臨床應用提供寶貴資料，並對阿茲海默氏症早期檢測及神經影像學相關文獻的累積有重要貢獻。再者，透過整合神經認知科學、腦神經影像學以及基因學等方式，來研究不同年齡族群的個體，將有助於建立一套早期辨認罹患阿茲海默氏症之工具的可能性。
Abstract: The Apolipoprotein E (APOE) e4 allele is the best-established genetic risk factor for sporadic Alzheimer’s disease, and is associated with cognitive changes as well as structural gray matter and functional brain changes in healthy individuals. Among neuropsychological studies that have reported APOE e4 allele related deficits, episodic memory and executive functioning have been shown to be particularly affected among e4 carriers. Furthermore, APOE has been implicated in brain mechanisms associated with white matter development and repair. Yet, rarely do these studies consider the effects of APOE e4 allele on cognitive performance and white matter changes systematically beyond the older populations. Hence, the key goal of the proposed study is to conduct a three-year study to investigate the potential role played by the APOE polymorphism on cognition, particularly memory and executive functioning, and white matter as well gray matter integrity in healthy young, middle-aged, and older adults. To achieve the goal, we will utilize theoretically-driven measures of neurobehavioral dysfunction that are sensitive to damage in neural structures and systems known to be involved in the early stages of Alzheimer’s disease. Moreover, we aim to apply state-of-the-art imaging techniques (i.e., Diffusion Spectrum Imaging which can overcome the crossing fibers issues encountered in Diffusion Tensor Imaging) and data analysis approach (i.e., FreeSurfer) to study the integrity of white and gray matter, and their relationship to the cognitive performance in the healthy but genetically at risk adults across lifespan. Taken together, the proposed study is significant not only for its potential clinical implications, but for its addition of valuable knowledge to the literature in early detection of Alzheimer’s disease and neuroimaging domains. By studying genetically at risk individuals who are at different developmental stages using a combined approach includes neurocognitive, neuroimaging and genetic data, the research results may emerge as a useful and recommended approach /protocol to identify at-risk individuals.