2011-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/701500摘要：在高齡化的國家中，失智症是日趨受到重視的疾病之ㄧ。近年來研究顯示，中高強度的有氧運動有助於改善知能障礙患者的整體認知功能，或是以雙項任務（dual-task）模式搭配肌力與平衡訓練，則可以改善其特定的認知功能。但這些療效的機制仍為未知，而運動訓練對於不同基因型的知能障礙者療效是否不同，目前亦尚未有研究探討。因此，本研究計畫主要目的為探討：（1） 探討有氧運動合併雙項任務訓練對改善輕度知能障礙與早期阿茲海默症患者的記憶與執行功能之療效；（2） 探討有氧運動合併雙項任務訓練是否對攜帶與不攜帶APOEε4 基因型的輕度知能障礙或早期阿茲海默症患者有不同之療效；（3） 探討有氧運動合併雙項任務訓練對改善輕度知能障礙與早期阿茲海默症患者的記憶與執行功能之療效機制，此療效機制含腦部組織結構完整性、腦部血流、血中Aβ1-40、Aβ1-42、胰島素阻抗性、血中細胞激素等生物標記之探討。本研究採評估者單盲隨機控制臨床試驗（single-blind randomized controlled trial）。預計徵召70 位輕度知能障礙或早期阿茲海默症患者，分層（stratified）隨機分配至實驗組與控制組。實驗組將接受為期12 週，每週3 次，每次90 分鐘的中強度有氧運動合併雙項任務訓練。控制組則接受為期12 週，每週3 次，每次90 分鐘的伸展與坐姿下活動訓練。兩組受試者訓練期與追蹤期（結束後3 個月）維持穩定用藥狀況，並在訓練前、訓練後、與訓練結束後3 個月，接受血中Aβ1-40 及Aβ1-42 的含量、血中胰島素含量、飯前血糖、血中細胞激素（TNF-α, IL-Iβ, IL-6, CRP）含量、大腦結構與腦部血流檢查，以及認知功能與雙項任務測試。將比較兩組受試者在各項測試與檢查之訓練前、後與追蹤期後的變化，以了解有氧運動合併雙項任務訓練對輕度知能障礙和早期阿茲海默症患者之療效與療效機制，以及APOEε4 基因型對運動訓練療效之可能影響。本研究結果可提供以運動訓練改善輕度知能障礙和早期阿茲海默症患者的認知功能之實證醫學依據，並探討其療效機制，將可作為未來對輕度知能障礙和早期阿茲海默症患者運動訓練設計與治療之參考，期能對國內此類患者有實質助益。<br> Abstract: Recent studies have shown that moderate-to-high intensity aerobic exercises are effectivein improving overall cognitive function in patients with cognitive impairment or dementia.Dual-task training programs also show positive effects on enhancing executive function inpatients with cognitive impairment. However, the biological mechanisms through which thesetraining effects are mediated remain largely unknown in humans. It also remains unclearregarding whether carrying APOEε4 genotype or not would influence the effects of aerobicexercises and dual-task training on cognitive function of these patients. Therefore, the threemain purposes of this study are:(1) to investigate the effects of a 3-month aerobic exercises combined with dual-tasktraining on memory and executive cognitive functions in patients with mildcognitive impairment (MCI) and in those with early Alzheimer’s disease (AD);(2) to compare the differences in training effects between patients who carry APOEε4genotype and those who do not carry this genotype; and(3) to investigate the biological mechanisms of the exercise training effects on memoryand executive cognitive function in these patients. The biological mechanisms ofinterest will include the blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose,cytokine (TNF-α, IL-Iβ, IL-6, CRP),integrity of brain fiber tracts, and cerebralblood flow.We will conduct a single-blind (assessor blinded) randomized controlled clinical trial. Atotal of 70 patients with MCI or AD will be recruited. The participants will be randomlyassigned to the experimental group or the control group using stratified randomization bymatching patient’s diagnosis. Both groups will receive one health education session and three90-minute exercise sessions per week for 12 weeks. For the experimental group, the exerciseprogram will include moderate intensity aerobic exercises and dual-task training; whereas forthe control group, the training program will include gentle stretching exercises and activitiesin sitting of mild intensity. Both groups will receive examinations on outcome variables,including blood Aβ1-40 and Aβ1-42 level, insulin, fasting glucose, cytokine (TNF-α, IL-Iβ,IL-6, CRP),integrity of brain fiber tracts, cerebral blood flow, cognitive function, and dualtask performance at baseline (week 0), post-training (week 12), and after a 3-month follow-upperiod (week 24). Differences on the aforementioned outcomes brought by the 12-weektraining programs will be compared between the experimental and control groups usingtwo-way (group x time) repeated measures of ANOVA. Intercorrelations among the changesin these outcomes will be analyzed to explore the possible biological mechanisms mediatingthe training effects. Exercise effects between patients who carry APOEε4 genotype andthose who do not will also be examined.Results of this study will provide relevant clinical evidence for the effects of aerobic exercises combined with dual-task training on patients with MCI and mild AD; and willprovide further understanding of the mechanisms mediating these effects輕度知能障礙早期阿茲海默症APOEε4基因型有氧運動雙項任務認知功能動作功能mild cognitive impairmentearly Alzheimer’s diseaseAPOEε4aerobic exercisedual-taskcognitive functionmotor function