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成年人之腦部灰質、白質和認知功能中的執行功能及記憶改變有關。然而，目前國內外尚未有研究探討認知訓練是否能有效提升帶有阿茲海默氏症危險基因之健康成年人的認知功能，以及相對應之腦部網絡連結和神經生物標記是否也會因此而改變。因此，本計劃希望透過為期三年的研究，針對帶有APOE e4 與 不帶有e4基因的健康老年與青年族群，探討認知訓練對於其認知功能、大腦網絡功能以及神經生物標記之短期與長期的影響。本研究採用雙盲隨機對照試驗的設計，並以與認知歷程相扣之認知作業做為認知訓練的工具，透過整合臨床與認知心理學、神經科學、腦神經影像學以及基因學等跨領域資料，期望可以深入探討認知訓練所帶來之行為的效果與其改變背後的機制。本研究成果除了可對臨床應用提供寶貴資料外，亦可提供正常與異常老化過程中預防認知退化之訓練方案的參考與建議，並對阿茲海默氏症早期預防醫學及神經影像學等相關文獻的累積有重要貢獻。
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 and white matter, and functional brain changes in healthy individuals. Among neuropsychological studies that have reported APOE e4 allele related deficits, executive functioning and memory has been shown to be particularly affected among e4 carriers. Yet, to our knowledge, no studies have investigated the effect of cognitive training on plasticity of cognitive function and its relationship with brain network connectivity and neurobiological markers in cognitively intact adults at gentic risk for Alzheimer’s disease. Hence, the key goal of the proposed study is to conduct a three-year longitudinal study to investigate the short-term and long-term plasticity in cognition, brain network connectivity, and neurobiological markers related to the cognitive training. To achieve the goal, we will conduct a double-blind and randomized controlled trial that utilizes cognitive process driven tasks to train a group of young and old individuals who are either APOE e4 carriers or noncarriers. Moreover, we aim to apply an interdisciplinary approach to study the brain mechanism underlying the behavioral changes related to the training program through applying state-of-the-art imaging techniques and collecting information related to neurobiological markers. 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 prevention of Alzheimer’s disease and neuroimaging domains. All the results may emerge as a useful and recommended approach/protocol to prevent cognitive declines during normal aging process or at a preclinical Alzheimer’s disease stage.
Alzheimer’s disease (AD)
apolipoprotein E (APOE)