体育活动对认知相对于载脂蛋白 E 基因型的影响（PAAD-2）：一项 II 期随机对照试验的研究方案。
The effect of physical activity on cognition relative to APOE genotype (PAAD-2): study protocol for a phase II randomized control trial.
机构信息
Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, NC, 27402, USA.
Under Armour, Baltimore, MD, 21209, USA.
出版信息
BMC Neurol. 2020 Jun 6;20(1):231. doi: 10.1186/s12883-020-01732-1.
BACKGROUND
By 2050, the prevalence of Alzheimer's disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. This randomized clinical trial aims to (a) test the causal relationship between PA and AD-associated cognitive function for persons with a family history of AD (FH+), (b) determine the moderating role of apolipoprotein epsilon 4 (APOE4) carrier status on cognition, and (c) assess cerebral structure, cerebral function, and putative biomarkers as mediators of the effects of PA on cognition.
METHODS
We are recruiting cognitively normal, middle aged (40-65 years) sedentary adults with FH+. Participants are randomly assigned to a 12-month PA intervention for 3 days/week or to a control group maintaining their normal lifestyle. Saliva samples are taken at pre-test to determine APOE genotype. At pre-, mid-, and post-tests, participants complete a series of cognitive tests to assess information-processing speed, verbal and visual episodic memory, constructional praxis, mnemonic discrimination, and higher-order executive functions. At pre- and post-tests, brain imaging and blood biomarkers are assessed.
DISCUSSION
We hypothesize that 1) the PA group will demonstrate improved cognition compared with controls; 2) PA-derived cognitive changes will be moderated by APOE4 status; and 3) PA-induced changes in neural and blood biomarkers will contribute to cognitive changes and differ as a function of APOE4 status. Our results may provide important insights into the potential of PA to preserve neurocognitive function in people with a heightened risk of AD due to FH+ and as moderated by APOE4 status. By using sophisticated analytic techniques to assess APOE as a moderator and neurobiological mechanisms as mediators across trajectories of cognitive change in response to PA, we will advance our understanding of the potential of PA in protecting against AD.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03876314. Registered March 15, 2019.
背景
到 2050 年，预计美国阿尔茨海默病（AD）的患病率将达到 1380 万。尽管全球研究努力，但尚未确定 AD 的治愈方法。因此，确定可以降低 AD 风险或延缓发病的预防策略至关重要。体育锻炼（PA）在这方面具有潜力。这项随机临床试验旨在：（a）测试具有 AD 家族史（FH+）的人 PA 与 AD 相关认知功能之间的因果关系；（b）确定载脂蛋白 Epsilon 4（APOE4）携带者状态对认知的调节作用；（c）评估大脑结构、大脑功能和潜在生物标志物作为 PA 对认知影响的中介。
方法
我们正在招募认知正常、中年（40-65 岁）久坐不动的 FH+成年人。参与者随机分配到为期 12 个月的每周 3 天的 PA 干预组或保持正常生活方式的对照组。在预测试时采集唾液样本以确定 APOE 基因型。在预测试、中测试和后测试时，参与者完成一系列认知测试，以评估信息处理速度、言语和视觉情景记忆、结构练习、记忆辨别和高级执行功能。在预测试和后测试时，评估脑成像和血液生物标志物。
讨论
我们假设：1）PA 组的认知表现将优于对照组；2）PA 引起的认知变化将由 APOE4 状态调节；3）PA 引起的神经和血液生物标志物的变化将有助于认知变化，并根据 APOE4 状态的不同而有所不同。我们的研究结果可能为 PA 提供重要的见解，以保留由于 FH+而处于 AD 高风险人群的神经认知功能，并由 APOE4 状态调节。通过使用复杂的分析技术来评估 APOE 作为调节因子和神经生物学机制作为对 PA 反应的认知变化轨迹的中介，我们将深入了解 PA 预防 AD 的潜力。
试验注册
ClinicalTrials.gov NCT03876314。2019 年 3 月 15 日注册。
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