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， 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）已显示出降低 认知能力下降，脑结构萎缩，以及患阿尔茨海默病和其他相关疾病的风险 痴呆症然而，尽管几十年的工作和建议，以提高锻炼的参与， 在有目的的锻炼中，PA的使用和参与并没有大大增加。与PA相比， 久坐行为（SB）或坐着的时间对老年痴呆症的风险受到的关注较少。sb可以 对健康有独立的生理影响，可能无法通过参与PA完全改善， 越来越多的证据表明SB可能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改变提供了一个关键目标，因为减少了 与增加老年人的锻炼水平相比，坐着的时间可能更容易实现。 在这项提案中，我们将确定在SB中花费的时间是否与大脑健康以及 患上了老年痴呆症和全因痴呆症在这里，我们重点关注SB对认知，大脑， 结构，和阿尔茨海默病的发病率在最大的前瞻性队列分析到目前为止，英国生物银行。 我们将分析SB标志物之间的关联，包括自我报告和可穿戴设备的客观测量。 加速度计，认知，大脑健康，以及阿尔茨海默病和全因痴呆症。这 一个独特的数据集将使我们能够确定大脑老化结果的最佳SB预测因子，包括阿尔茨海默氏症 疾病的发病率，以便干预措施可以集中在减少老年人SB的最有害方面。 使用此数据集沿着三个复制数据集，我们将测试我们的总体假设，即高水平 SB与认知能力下降、大脑健康状况较差和阿尔茨海默病增加有关 在PA中的补充参与不能完全缓解的风险。为了验证这一假设，本提案将 解决以下具体目标：1）确定SB如何与阿尔茨海默病事件相关， 全因痴呆，2）评估SB与以下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的风险，和3）调查如何取代SB 在不同的PA水平上花费的时间改变了SB和阿尔茨海默病风险之间的关联。通过 评估一种新的，全面的SB标志物，并测试它们与认知，大脑， 结构和阿尔茨海默病的风险，这项建议提供了一个独特的机会，以获得所需的关键数据 帮助推进开发有效预防阿尔茨海默病的干预措施的努力。

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.