Inactivity, sedentary behavior, and the risk for Alzheimer’s disease in middle aged to older adults

摘要 阿尔茨海默病是一种破坏性的进行性神经退行性疾病，会导致严重的损失 大脑和认知功能。迫切需要确定能够降低风险的因素，包括 可改变的生活方式行为。运动和体力活动(PA)在降低高血压发病率方面显示出了希望。 认知功能减退、脑结构萎缩、阿尔茨海默病的风险及其他相关疾病 痴呆症。然而，尽管做了几十年的工作，并建议提高运动参与度， PA和有目的锻炼的参与度并没有显著增加。与PA相比，PA的效果 久坐行为(SB)或久坐在阿尔茨海默病风险上的时间受到的关注较少。某人可能 对健康有独立的生理影响，而参与PA可能不会完全改善这种影响；以及 越来越多的证据表明，某人可能会对认知和大脑结构产生有害影响。理解 SB对阿尔茨海默病风险的影响可能为行为调整提供一个关键靶点，因为它减少了 与增加老年人的运动量相比，坐着的时间可能更容易实现。 在这项建议中，我们将确定在某人身上度过的时间是否与大脑健康和 罹患阿尔茨海默氏症和全因痴呆症。在这里，我们重点研究SB对认知、大脑的影响 结构和阿尔茨海默病发病率在迄今为止分析过的最大的前瞻性队列中，英国生物库。 我们将分析包括自我报告在内的SB标记与可穿戴设备的客观测量之间的关联 加速计、认知、大脑健康、阿尔茨海默病和全因痴呆症事件。这 独特的数据集将允许我们确定包括阿尔茨海默氏症在内的大脑老化结果的最佳SB预测因子 疾病发生率，以便干预措施可以集中在减少老年人SB最有害的方面。 使用此数据集和三个复制数据集，我们将测试我们的总体假设，即高水平 与认知功能减退、大脑健康状况较差和阿尔茨海默病增加有关 在PA中的互补参与不能完全缓解的风险。为了检验这一假设，这项提议将 解决以下具体目标：1)确定SB如何与阿尔茨海默病事件和 全因痴呆症，2)评估SB与各方面之间的横断面和前瞻性关系 认知和大脑结构与阿尔茨海默病风险相关，以及3)研究如何取代某人 随着时间的推移，PA水平改变了SB与阿尔茨海默病风险之间的联系。通过 评估一组新的、全面的SB标记，并测试它们与认知、大脑的关联 结构和阿尔茨海默病风险，这一建议提供了一个独特的机会来获得所需的关键数据 帮助推进为阿尔茨海默病预防制定有效干预措施的努力。

Abstract Alzheimer’s disease is a devastating progressive neurodegenerative disease that leads to a profound loss of brain and cognitive functions. There is an urgent need to identify factors that can decrease risk, including modifiable lifestyle behaviors. Exercise and physical activity (PA) have shown promise in reducing rates of cognitive decline, brain structural atrophy, and risk of developing Alzheimer’s disease and other related dementias. However, despite decades of work, and recommendations to improve exercise participation, levels of PA and engagement in purposeful exercise have not increased greatly. In contrast to PA, the effect of sedentary behavior (SB) or time spent sitting on Alzheimer’s disease risk has received less attention. SB may have independent physiological effects on health which may not be fully ameliorated by engaging in PA, and there is growing evidence that SB may have detrimental effects on cognition and brain structure. Understanding the effects of SB on Alzheimer’s disease risk may provide a key target for behavioral modification since reducing time spent sitting may be easier to implement compared to increasing exercise levels in older adults. In this proposal, we will determine whether time spent in SB is associated with brain health and the risk of developing Alzheimer’s disease and all-cause dementia. Here, we focus on the effects of SB on cognition, brain structure, and Alzheimer’s disease incidence in the largest prospective cohort analyzed to date, the UK Biobank. We will analyze associations between markers of SB including self-report and objective measures from wearable accelerometers, and cognition, brain health, and incident Alzheimer’s disease and all-cause dementia. This unique dataset will allow us to determine the best SB predictors of brain aging outcomes, including Alzheimer’s disease incidence so that interventions can focus on reducing the most harmful aspects of SB in older adults. Using this dataset along with three replication datasets, we will test our overarching hypothesis that high levels of SB are associated with increased cognitive decline, poorer brain health, and increased Alzheimer’s disease risk that is not fully mitigated by complementary engagement in PA. To test this hypothesis, this proposal will address the following specific aims: 1) to determine how SB is associated with incident Alzheimer’s disease and all-cause dementia, 2) to evaluate the cross-sectional and prospective relationships between SB and aspects of cognition and brain structure associated with Alzheimer’s disease risk, and 3) to investigate how displacing SB with time spent in different PA levels modifies the association between SB and Alzheimer’s disease risk. By evaluating a novel, comprehensive set of SB markers and testing their associations with cognition, brain structure, and Alzheimer’s disease risk, this proposal provides a unique opportunity to obtain key data needed to help advance efforts in developing effective interventions for Alzheimer’s disease prevention.