運動對具心血管危險因子之中老年人的心血管危險因子、心肺適能、腦結構與活化、 及轉換任務表現的效果及效果間之關係

Abstract

研究背景與目的:規律運動可能可預防心血管危險因子對腦結構、腦活化、與認知功能的負面影響。本研究的目的為探討對具心血管危險因子的中老年人，有氧、太極拳、與伸展運動對四類成效參數－心血管危險因子、心肺適能、腦結構及活化、與認知轉換任務表現－的效果，及運動訓練後腦部結構與功能之改變是否為改善之心血管危險因子與心肺適能與進步之轉換任務表現間的中介因子。 研究方法：本研究資料來自一個評估者單盲之隨機對照臨床試驗（NCT試驗編號：NCT03275038），有70位(45至79歲)具心血管危險因子的中老年人參與該試驗。受試者被隨機分配至有氧組、太極組、或伸展組，接受每週三次，每次一小時，為期十二週之監督下輕至中強度運動訓練。運動訓練前後，受試者均進行抽血檢測、心肺運動功能測試、腦部磁振照影、及認知轉換表現測試。以二因子重複測量變異數分析比較三組間各參數訓練效果之差異。使用各參數後測數值減去其前測數值計算訓練前後各參數改變量。使用淨相關分析，探討心血管危險因子及心肺適能改變量與腦部體積與活化改變量及轉換任務表現改變量間的相關性，控制年齡、性別、教育程度。使用中介分析，探討腦結構及活化的改變，是否顯著中介訓練後改善的心血管危險因子或提升的心肺適與進步的轉換任務表現間的關係，控制年齡、性別、教育程度。與腦結構相關的分析則增加控制估計全顱內體積。此論文採完成者分析法，完成全程研究者之資料才會納入分析 結果: 總共56位受試者（平均年齡64.3 ± 7.4歲，37位女性）完成此研究。三種運動，不論運動類別，均可有效降低部分心血管危險因子、一致性的提升心肺適能、與提升轉換任務表現，並降低左側運動輔助區轉換情境下之活化（p均< 0.05）。因三種運動對成效參數之效果多無組間差異，本研究之淨相關與中介分析是將三組資料合併後作的分析。運動訓練後，同半胱胺酸降低量與轉換任務表現進步量呈顯著正相關（r= 0.345, p= 0.011）；舒張壓下降量與轉換任務下海馬迴（r= 0.438, p= 0.001）與杏仁核活化（r= 0.419, p= 0.002）下降量呈顯著正相關。心肺適能上升量與左側額下回體積（r= 0.309, p= 0.026）上升量呈顯著正相關。運動訓練後，右側海馬迴腦活化下降量可完全中介並促進舒張壓下降及轉換任務進步間的關係（間接效果= 0.020, 95%CI= [0.001, 0.047]）。運動訓練後，左側額下回腦體積上升量可完全中介並增強心肺適能上升及轉換任務進步間的關係（間接效果= -0.124, 95%CI= [-0.347, -0.005]）。 討論:三個月規律之中至輕度運動，無論是有氧、太極、或伸展，對具心血管危險因子的中老年人，均可改善其部份心血管危險因子，提升其心肺適能及轉換任務表現。改善的心血管危險因子或提升的心肺適能可分別透過腦活化下降及腦體積上升中介轉換任務表現的進步。透過非必要腦活化下降的中介，亦即更有效的腦血管耦合機制，可使改善的心血管危險因子促進轉換任務表現。透過增加特定前額葉腦體積之中介，上升的心肺適能可提升轉換任務表現。 結論:在具心血管危險因子的中老年人，規律運動後，其腦活化及腦體積之變化可有效中介其心血管危險因子與心肺適能之改善與轉換任務表現之進步間的關係。

Background and purposes: Engaging in regular exercises may prevent the negative impacts of cardiovascular risks (CVRs) on brain structures, brain activation, and cognitive functions. This study examined the effects of aerobic training (AT), Tai Chi Chuan (TCC), and stretching (ST) exercises on four types of outcome measures, including measures of CVRs, cardiorespiratory fitness (CRF), brain structures and functional activation, and task-switching performances; and investigated whether changes in brain structures and brain activation would mediate the relationships of the changes in CVRs and CRF with the changes in task-switching performances after exercise training in middle-aged and older adults with CVRs. Methods: Data analyzed in this study came from an assessor-blind randomized controlled clinical trial (Trial no: NCT03275038), in which 70 sedentary middle-aged and older adults with CVRs (aged 45-79 years) were enrolled and were randomly assigned to the AT, TCC, or ST group. All three groups underwent one-hour supervised mild-to-moderate intensity exercise triweekly for 12 weeks. Blood tests for measuring CVRs, cardiorespiratory exercise tests for measuring CRF, MRI scans for collecting brain structures and functional images, and task-switching performances were all performed before and after the 12-week exercise training. The changes in all outcome measures were calculated as post-test values minus the pre-test values. Two-way (group x time) repeated measures ANOVA was used to compared group differences in training effects on outcome measures. Partial correlations were applied for the associations of the changes in CVRs and CRF with the changes in brain volumes and activation and in task-switching performances. Mediation analysis was applied to determine whether the changes in brain volumes and activation would mediate the relationships between the changes in CVRs and CRF with the changes in task-switching performances, controlling for age, sex, and education. Brain volumetric related analysis was additionally adjusted for the estimated total intracranial volume. The completer analysis approach was used in this study Only data of participants who completed the trial were used in this study. Results: Fifty-six participants (64.3 ± 7.4 years old, 37 women) completed the trial. After training, all three groups significantly improved CRF, some CVRs, and task-switching performances, and decreased brain activation at the left supplementary motor area while performing task-switching after the 12-week training (all p< 0.05). Because there were no group differences in training effects on most outcome measures, data from the three groups were pooled for correlation and mediation analyses. Greater reductions in the homocysteine level was correlated with greater improvement in task-switching performance (r= 0.345, p= 0.011). Greater reductions in diastolic blood pressure was correlated with greater reductions in brain activation at the right hippocampus (r= 0.438, p= 0.001) and the right amygdala (r= 0.419, p= 0.002) for task-switching. Greater increases in CRF was correlated with greater increases of the left inferior frontal gyrus volume (r= 0.309, p= 0.026). Reduced brain activation at the right hippocampus mediated and facilitated the positive relationship between the improved CVR and the improvement in task-switching performances (Indirect effect= 0.020, 95%CI= [0.001, 0.047]). The enlarged brain volume at the left inferior frontal gyrus fully mediated and strengthened the beneficial relationship between the increased CRF and the improvement in task-switching performances (Indirect effect= -0.124, 95%CI= [-0.347, -0.005]). Discussion: Three-month regular mild-to-moderate exercises, whether being aerobic, TCC, or stretching, resulted in some improvements in CVRs and robust improvement in CRF and cognitive task-switching in middle-aged and older adults with CVRs. Changes in brain activation and structures mediated the relationships between changes in CVR and CRF with changes in task-switching performance, respectively. Through decreasing unnecessary brain activation, which may imply a more efficient cerebrovascular coupling mechanism, improved CVR promoted task-switching performances. Through enlarging a specific prefrontal volume, increased CRF enhanced task-switching performances. Conclusions: In middle-aged and older adults with CVRs, after engaging in regular exercises, their changes in brain activation and structures could effectively mediate the relationships between their improvement in CVRs and CRF with their improvement in task-switching.