Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive Outcomes

项目摘要 阿尔茨海默病和相关痴呆症（ADRD）的患病率，目前估计影响4700万人 预计到2050年，全球人口将增加两倍。对其病因的认识不足阻碍了进展 治疗和预防策略。有证据表明心血管疾病 (CVD)各种CVD危险因素与痴呆的发病率密切相关。血管危险因素 很容易识别，而且经常可以修改。因此，发现CVD之前的血管危险因素， 认知功能障碍或下降将显著提高我们对血管性疾病病因学的理解， ADRD。心率变异性（HRV）和QT间期变异性（QTV），源自心电图（ECG） 分析，是对心脏的自主控制的公知指标。HRV较低，QTV较高，表明 心脏自主神经功能差，是未来心血管发病率和死亡率的强有力的预测。 值得注意的是，在ADRD和轻度认知障碍（MCI）中观察到较低的HRV和QT异常。 因此，研究HRV和QTV可能为了解心脏自主神经功能在心脏病中的作用提供有价值的信息。 痴呆症的发展。然而，在大多数研究中，HRV和QTV是从标准短期ECG导出的 （持续时间从10秒到几分钟不等），由于 稳定性的要求。虽然Zio XT Patch等可穿戴设备允许心电图记录高达14 天的持续时间，用于分析HRV和QTV的方法是基于平稳性假设，导致 当应用于这种额外的长期记录时，可能无法解释或误导的措施。因此，在本发明中， 需要创新的信号分析工具来充分利用这些ECG的潜力。最近，一个新的信号 处理方法是专门开发的，以获得新的措施，心率变异性和QTV从额外的长期 更好地代表真实环境中心脏自主神经功能的ECG。此K01的主要目标 指导职业发展奖是在一个大型的，持续的队列中实施这一创新的分析工具 老年人研究，从最近收集的14天Zio Patch中获得HRV和QTV的新测量值 录音.在目标1中，我们将评估这些新措施与认知表现的关联， 流行或偶发MCI或痴呆的风险。在目标2中，我们将确定它们的日变化是否与以下因素有关： 认知能力更差或有MCI或痴呆的风险。最后，我们将利用最近的神经影像学数据， 确定超长HRV或QTV是否与神经影像学相关的参与者子集 ADRD或脑血管疾病的生物标志物。如果成功，拟议的研究可能会提供深入了解 将血管危险因素和CVD与ADRD联系起来的机制，并可能识别心脏自主神经功能 作为可修改的干预目标。此外，该K01奖将提供必要的资源，以支持 候选人在日益重要的公共卫生领域过渡到独立的研究生涯。

Project Summary Prevalence of Alzheimer’s disease and related dementias (ADRD), currently affecting an estimated 47 million people worldwide, is expected to triple by 2050. A poor understanding of its etiology has hindered progress toward treatments and preventive strategies. Several lines of evidence suggest that cardiovascular diseases (CVD) and various CVD risk factors are strongly associated with incidence of dementia. Vascular risk factors are easily identifiable and often modifiable. Therefore, discovery of vascular risk factors that precede CVD and cognitive impairment or decline would significantly enhance our understanding of the vascular etiology of ADRD. Heart rate variability (HRV) and QT interval variability (QTV), derived from electrocardiogram (ECG) analysis, are well-known indices of autonomic control over the heart. Lower HRV and higher QTV, indicating worse cardiac autonomic function, are strongly predictive of future cardiovascular morbidity and mortality. Notably, lower HRV and QT abnormalities have been noted in ADRD and mild cognitive impairment (MCI). Thus, the study of HRV and QTV may provide valuable insight into the role of cardiac autonomic function in the development of dementia. However, in most studies HRV and QTV are derived from standard short-term ECG (ranging from 10 seconds to several minutes duration), which does not reflect real-world conditions due to the requirement of stationarity. Although wearable devices such as Zio XT Patch allow ECG recording of up to 14 days duration, methods used to analyze HRV and QTV are based on the stationarity assumption, resulting in measures that may be uninterpretable or misleading when applied to such extra long-term recordings. Thus, innovative signal analysis tools are required to utilize the full potential of these ECGs. Recently, a new signal processing method was developed specifically to derive novel measures of HRV and QTV from extra long-term ECG that better represent cardiac autonomic function in real-world settings. The primary goal of this K01 mentored career development award is to implement this innovative analysis tool in a large, ongoing cohort study of older adults to derive novel measures of HRV and QTV from recently collected 14-day Zio Patch recordings. In Aim 1, we will evaluate the association of these novel measures with cognitive performance and risk of prevalent or incident MCI or dementia. In Aim 2, we will determine if their diurnal variation is related to worse cognitive performance or risk of MCI or dementia. Finally, we will leverage recent neuroimaging data in a subset of participants to determine if extra long-term HRV or QTV is associated with neuroimaging biomarkers of ADRD or cerebrovascular disease. If successful, the proposed study may provide insight into the mechanisms linking vascular risk factors and CVD to ADRD, and potentially identify cardiac autonomic function as a modifiable intervention target. In addition, this K01 award will provide the resources necessary to support the Candidate’s transition to an independent research career in an area of growing public health importance.