Variability and Volume of Day-to-Day Lifestyle Activity in Sustaining Cognitive Function among Insufficiently Active Older Adults at Risk for Alzheimer's Disease and Related Dementias

阿尔茨海默病和相关痴呆症(ADRD)发病率的不断上升给社会带来了巨大的经济负担 社会和家庭的负担，构成了美国最大的医疗成本支出。到目前为止，医学上 预防和治疗ADRD的方法收效甚微。非药理预防 体力活动等策略有望维持认知，从而降低老年人的ADRD风险 成年人。不幸的是，对于许多老年人来说，从事推荐的高等职业生涯是不可行和实际的。 高强度的体育活动(或有氧运动)，特别是那些行动不便、身体障碍、 和易患的健康状况。现有证据表明，即使是从事低强度的生活方式 散步等活动可能有益于认知健康。然而，这部文献只专注于 光强度体力活动(LPA)或步骤的总量或平均体积，并确定为小到中等 对认知的影响。除实施的总量外，LPA或步骤的日常可变性(或稳定性) 也代表了潜在地可以放大认知益处的行为目标，但这个变量没有 在文献中得到了检验。利用实验医学的方法，这项提议将架起知识的桥梁 通过确定老年人的LPA/STEPS的每日变异性和体积是否联合预测他们的 近端和远端认知功能。这项研究将招募不同种族的老年人(60岁以上) 不够活跃，发展ADRD的风险更高。符合条件的参赛者将穿着 30天的加速计，以评估每个人每天LPA/步数的典型变异性和体积。他们 将在相同的30天内完成每日电子调查，以评估他们的日常压力、睡眠和社交 订婚。这些因素影响老年人的日常体育活动和认知，因此它们将是 在估计每个人的典型LPA和步骤模式时考虑(建模)。经过30天的监测 在此期间，参与者将在第31天、2.5个月和4个月时完成三项后续认知测量。 这些认知测量包括经过验证的实验室内和基于智能手机的工具(MoCA、Scale、NIH资助的 M2C2应用程序)。最后，这项研究将检查子组差异(基于人口统计)是否存在于 日常生活方式活动模式(LPA/STEPS的变化量和数量)与认知之间的关联 功能。为了加强我们研究结果的严谨性，我们将在我们的 分析。该程序考虑了不平衡数据集中的不确定性，这可以增强估计 精确度和提供可靠的结果。第一项研究的目的是确定一天的变化和数量是否 LPA/STEPS是维持ADRD风险老年人近端和远端认知功能的联合靶点。 第二个目的是调查这些关联中是否存在性别、性别、年龄和种族/民族差异 LPA/STEP模式与认知功能之间的关系。调查结果有可能确定可实现和可扩展的 可用于未来疗效试验的行为目标，以降低老年人日常生活中的ADRD风险。

The escalating incidence of Alzheimer’s disease and related dementias (ADRD) places a tremendous economic burden on society and families, making up the largest healthcare cost expenditure in the US. To date, medical approaches for preventing and treating ADRD have yielded limited success. Non-pharmacological preventive strategies, such as physical activity, hold promise for sustaining cognition and thus reducing ADRD risks in older adults. Unfortunately, it is not feasible and practical for many older adults to engage in the recommended higher- intensity physical activities (or aerobic exercise), especially for those with mobility limitations, physical barriers, and predisposing health conditions. Existing evidence suggests that even engaging in lower-intensity lifestyle activities, such as walking, may benefit cognitive health. However, this literature has exclusively focused on the total amount or mean volume of light-intensity physical activity (LPA) or steps and identified small-to-moderate effects on cognition. Beyond the total volume performed, the day-to-day variability (or stability) of LPA or steps also represents a behavioral target that potentially can amplify the cognitive benefits, but this variable has not been tested in the literature. Using an experimental medicine approach, this proposal will bridge the knowledge gap by determining whether older adults’ daily variability and volume of LPA/steps jointly predict their proximal and distal cognitive function. This study will recruit ethnically diverse older adults (ages 60+) who are insufficiently active and have higher risks for developing ADRD. Eligible participants will wear an accelerometer for 30 days to estimate each person’s typical variability and volume of their daily LPA/steps. They will complete daily e-surveys during the same 30-day period to assess their daily stress, sleep, and social engagements. These factors influence older adults’ daily physical activity and cognition, so they will be considered (modeled) when estimating each person’s typical LPA and step patterns. After the 30-day monitoring period, participants will complete three follow-up cognitive measures on Day 31, at 2.5 months, and 4 months. These cognitive measures involve validated in-lab and smartphone-based tools (MoCA, scales, NIH-funded M2C2 app). Lastly, this study will examine whether subgroup differences (based on demographics) exist in the proposed associations between daily lifestyle activity patterns (variation and volume of LPA/steps) and cognitive function. To enhance the rigor of our study findings, we will apply the novel MixWILD statistical program in our analysis. This program accounts for uncertainties in unbalanced datasets, which can enhance estimation precision and provide reliable results. The first study aim is to determine if both variation and volume of daily LPA/steps are joint targets for sustaining proximal and distal cognitive function in older adults at risk for ADRD. The second aim is to investigate if there are sex, gender, age, and race/ethnicity differences in the associations between LPA/step patterns and cognitive function. Findings have the potential to identify achievable and scalable behavioral targets that can be engaged in future efficacy trials to reduce ADRD risks in older adults’ daily lives.