Breaking prolonged sitting with high-intensity interval training to improve cognitive and brainhealth in older adults: A pilot feasibility trial

摘要 年龄是AD的主要风险因素，影响到约580万美国人。增加体力活动(PA)可能 将阿尔茨海默病(AD)和AD相关痴呆的患病率降低11%。然而，大多数人 老年人(54%)仍然缺乏身体活动。传统的PA干预不能减少过度坐着 上了年纪的人。特别是，连续坐20分钟或更长时间(即长时间坐着)会显著减少 额顶脑功能和注意力控制。因此，老年人习惯性长时间坐着的水平较高 (每天5小时)可能会导致额顶脑功能效率随着年龄的增长而下降，这是负面的 影响对情节记忆的注意力控制和巩固。因此，巴勒斯坦权力机构的干预措施将加强 老年人的额顶和认知功能也应该以减少长时间坐着为目标。然而，没有 旨在减少长时间坐着和改善额顶脑功能的有效PA干预， 注意力控制和情景记忆是存在的。为了有效，这种干预措施应该针对这些机制 PA对大脑功能的潜在影响。单次服用PA被认为可以增强额顶脑功能 通过刺激蓝斑脑区去甲肾上腺素的时相释放。具体地说，PA刺激 周围迷走神经通过增加外周儿茶酚胺的水平。利用PA强度作为 外周儿茶酚胺增加的主要限制因素，我们提出了一种试点随机交叉 比较两种情况的可行性试验，每种情况持续3.5小时：每30分钟休息6分钟(HIIT 休息)，并用6分钟的社交互动(SIT)打断坐着，以解决三个目标：(1)评估可行性， HIIT中断的可接受性、保真度和安全性以改善神经认知功能；(Ii)量化差异 不同条件下P3b波幅和潜伏期的变化；(3)探讨不同条件下的差异 注意控制、情景记忆、额顶叶和默认模式的功能连接(FC) 网络。我们将对54名老年人(60-75岁)按平衡顺序管理这些条件。我们会 使用事件相关电位的P3b成分作为主要结果，因为它是 额顶顶脑功能和大脑去甲肾上腺素相移指数(例如，对PA的反应) 放手。它也可靠地受到运动的调节。接下来，我们将在额顶模式和默认模式下测量FC 大脑网络，因为它们受到大脑去甲肾上腺素的调节，并支持注意力控制和 分别是情节记忆。此外，这些网络中的FC可以通过单轮PA来改善，但是 随着年龄的增长而下降。这些结果将揭示短时HIIT是否可以作为定期增强的模型 脑功能和认知，通过在慢性干预中探测大脑去甲肾上腺素的释放。我们的长期合作 目的：探讨HIIT损伤对蓝斑完整性、额顶叶功能、 认知健康和认知受损老年人的认知功能受到年龄和AD的影响。

Abstract Age is the major risk factor for AD, which affects ~5.8 million Americans. Increasing physical activity (PA) could decrease the prevalence of Alzheimer’s Disease (AD) and AD Related Dementias by 11%. Yet, the majority of older adults (54%) remain physically inactive. Traditional PA interventions do not reduce excessive sitting in older adults. In particular, sitting continuously for 20 min or longer (i.e., prolonged sitting) can acutely reduce frontoparietal brain function and attentional control. Thus, habitually high levels of prolonged sitting in older adults (5 h/day) may contribute to the declining efficiency of the frontoparietal brain function with age, negatively affecting attentional control and consolidation of episodic memories. Accordingly, PA interventions to enhance frontoparietal and cognitive function in older adults should also target reducing prolonged sitting. However, no effective PA interventions designed to reduce prolonged sitting and improve frontoparietal brain function, attentional control, and episodic memory exist. To be effective such interventions should target the mechanisms underlying PA effects on brain function. A single bout of PA is thought to enhance frontoparietal brain function by stimulating phasic release of cerebral norepinephrine from the locus coeruleus. Specifically, PA stimulates vagus nerve in the periphery by increasing levels of peripheral catecholamines. Capitalizing on PA intensity as the major limiting factor in peripheral catecholamine increase, we propose a pilot randomized crossover feasibility trial to compare 2 conditions lasting 3.5 h each: sitting interrupted by 6-min HIIT every 30 min (HIIT Breaks), and sitting interrupted by 6-min social interactions (SIT) to address 3 aims: (i) to assess feasibility, acceptability, fidelity, and safety of HIIT Breaks to improve neurocognitive function; (ii) to quantify the differences between conditions in the change in P3b amplitude and latency; (iii) to explore the differences between conditions in attentional control, episodic memory, and functional connectivity (FC) of the frontoparietal and default mode networks. We will administer the conditions in a counterbalanced order to 54 older adults (60-75 years). We will use the P3b component of an event-related potential as a primary outcome because it is a known marker of frontoparietal brain function, and an index of phasic shifts (e.g., in response to PA) in cerebral norepinephrine release. It is also reliably modulated by exercise. Next, we will measure FC in the frontoparietal and default mode brain networks because they are modulated by cerebral norepinephrine, and support attentional control and episodic memory, respectively. Furthermore, FC in these networks can be improved with a single bout of PA but declines with age. These results will reveal if short bouts of HIIT can be used as a model to regularly enhance brain function and cognition, by probing cerebral norepinephrine release in a chronic intervention. Our long-term objective is to test the chronic effects of HIIT breaks on the integrity of the locus coeruleus, frontoparietal function, and cognitive functions affected by aging and AD in cognitively healthy and cognitively impaired seniors.