十二週有氧運動對於不同年齡群之大腦抑制控制與鐵沈積之神經影像研究

Abstract

全球老年人口逐年增加，老年群體罹患失智風險亦隨之上升，對於整體社經層面產生負面影響，使得健康老化顯得格外重要。為了達到健康老化之目標，體育鍛煉已被證明是一種對於提升年長者認知功能具備潛力的介入措施，可以防止大腦的神經髓鞘損壞、保持血管彈性、避免鐵沈積，從而維持認知功能。在與生活品質密切相關之認知功能中，高齡者的抑制控制能力已被證實可透過有氧運動而有所提升。然而，目前的證據顯示不同運動的持續時間對於大腦的神經可塑性影響並不一致，因此未有明確結論。另一方面，過去已有證據指出腦中的鐵沈積會降低老化大腦的認知功能，而年長者提升每日活動量可削弱鐵沈積與認知功能的關係，暗示體育活動對於清除大腦鐵沈積並提升認知功能的可能性。

為了回應上述兩項研究議題，我們對年輕成人和年長者進行了為期十二週的運動介入，使用數值Stroop任務和功能性磁振造影重複測量不同面向的抑制控制功能（促進和干擾效應）。對於大腦鐵沈積的部分，則使用定量磁化率影像量測不同年齡層的大腦鐵沈積數值，並觀察其中的年長者經過十二週運動介入之鐵沈積數值變化與認知行為表現的關係。此外，除了上述影像資訊，將使用功能性磁振造影於高碳酸血症期間獲得血管反應力，紀錄血管資訊。

結果顯示，經過 12 週的運動後，抑制控制的行為表現提升，可能源自於額頂葉網路和預設模式網路效應。在年輕人中，六週的運動增加了右上內側額葉回的激活，與干擾效應中的RT 減少相關，但在第二個運動階段（六至十二週），左上內側額葉回的活化減少腦回與促進效應的反應時間減少相關。 在老年人中，前六週的介入導致額下回、頂下回和預設模式網路區域的活化減少，這與干擾效應的反應時間減少有關。 儘管如此，年長者在第二個介入階段，只有視覺區域表現出活動增加，這與幹擾中 RT 的減少有關。而在鐵沈積的結果中，杏仁核, 前、中扣帶迴, 海馬迴, 蒼白球, 海馬旁迴, 殼核的鐵沈積數值受到年齡增長而上升，卻僅發現海馬迴的鐵沈積於運動六週後顯著下降，而其鐵沈積的下降反映情緒識別任務的準確率提升。另外，血管反應力沒有年齡、運動之顯著差異。

除了運動介入的兩個階段間存在獨特的大腦可塑性外，本研究還表明老年組在運動幹預的前六週內獲得了更多的認知益處； 然而，年輕組的認知能力介入六週後才得到更多改善。這些發現不僅證實了有氧運動對抑制功能與老化鐵沈積的益處，而且還暗示了年齡與運動對大腦可塑性的促進和干擾的交互作用。

The global aging population is increasing yearly, and if physical and cognitive functions decline, the growing elderly population may have negative implications for society. This underscores the importance of healthy aging. With aging, physiological factors such as neural demyelination, decreased vascular elasticity, and iron deposition contribute to age-related decline in cognitive function. Physical exercise has been demonstrated as a potential intervention to enhance cognitive function in older adults.

Specifically, executive functions crucial for the quality of life in older people, such as inhibitory functions, may benefit from aerobic exercise. Despite neuroimaging evidence indicating enhanced inhibitory functions after aerobic exercise, the neural plasticity patterns associated with different durations of exercise remain inconsistent. Moreover, iron deposition has been linked to cognitive decline in the aging brain, and increased daily physical activity in older adults may mitigate the relationship between iron deposition and cognitive function. This suggests that physical exercise may clear brain iron deposition and enhance cognitive function. Therefore, we conducted a 12-week exercise intervention in young and elderly adults, assessing inhibitory functions using the Numerical Stroop task and functional magnetic resonance imaging (fMRI) to measure different aspects (facilitation and interference effects) of inhibitory function.

For brain iron deposition, Quantitative Susceptibility Mapping (QSM) was used to quantify iron deposition values in different age groups. Mainly, the relationship between changes in iron deposition values after 12 weeks of exercise intervention and cognitive performance was observed in older people. Additionally, fMRI was employed to obtain vascular reactivity during hypercapnia, recording vascular information.

Results showed that performance enhanced after 12 weeks of exercise due to effects on the frontoparietal and default mode network. In young adults, the first six weeks of exercise, increased activation in the right superior medial frontal gyrus, correlated with a reduction in interference-related RT. However, in the second intervention stage (weeks six to twelve), decreased activation in the left superior medial frontal gyrus and visual areas was positively correlated with reduced RT in facilitation. In older adults, the initial six weeks of intervention led to reduced activation in regions of the inferior frontal gyrus, inferior parietal gyrus, and default mode network, correlated with reduced RT in interference. Nevertheless, in the second intervention stage, only visual areas exhibited increased activity in older adults, related to reduced RT in interference. In the results of iron deposition, the susceptibility increased with age in the amygdala, anterior cingulate, middle cingulate, hippocampus, pallidum, parahippocampal, and putamen. However, a significant decrease in hippocampal iron deposition was observed after six weeks of exercise, reflecting an improvement in the accuracy of the Emotion Recognition Task. Furthermore, there were no significant differences in cerebrovascular reactivity based on age or exercise.

Beyond the unique brain plasticity observed between the two stages of exercise intervention, this study indicates that the elderly group obtained more cognitive benefits in the initial six weeks of exercise intervention; however, the cognitive ability of the young group improved after six weeks of intervention. These findings confirm the benefits of aerobic exercise for inhibitory functions and aging-related iron deposition and suggest the interactive effects of age and exercise on brain plasticity.