Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive Outcomes

项目摘要 阿尔茨海默病和相关痴呆症的患病率，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。 用于治疗和预防策略。多条证据表明，心血管疾病 心血管疾病(CVD)和各种心血管危险因素与痴呆症的发病率密切相关。血管危险因素 很容易识别，而且经常是可修改的。因此，发现心血管疾病之前的血管危险因素和 认知障碍或认知功能下降将显著提高我们对血管病因学的理解。 阿德勒。心率变异性(HRV)和QT间期变异性(QTV) 分析，是众所周知的自主控制心脏的指标。较低的心率变异性和较高的QTV，表明 心脏自主神经功能较差，对未来心血管疾病的发病率和死亡率有很强的预测作用。 值得注意的是，ADRD和轻度认知损害(MCI)患者的HRV和QT异常较低。 因此，心率变异性和QTV的研究可能为了解心脏自主神经功能在高血压中的作用提供有价值的见解。 痴呆症的发展。然而，在大多数研究中，HRV和QTV是从标准的短期心电中得出的 (持续时间从10秒到几分钟不等)，这不能反映真实世界的情况，因为 对平稳性的要求。尽管像Zio XT Patch这样的可穿戴设备允许多达14次的心电记录 天数持续时间，用于分析HRV和QTV的方法基于平稳性假设，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， 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，以从超长期的HRV和QTV获得新的测量方法 在真实世界中更好地反映心脏自主神经功能的心电图。这款K01的主要目标是 指导职业发展奖是在大规模、持续的队列中实施这一创新的分析工具 从最近收集的14天Zio贴片中获得HRV和QTV新指标的老年人研究 录音。在目标1中，我们将评估这些新测量与认知表现和 患上或发生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 认知能力差或患MCI或痴呆症的风险。最后，我们将利用最新的神经成像数据 一组参与者，以确定额外的长期HRV或QTV是否与神经成像有关 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对 血管危险因素和心血管疾病与ADRD的联系机制，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，这项K01奖项将提供必要的资源，以支持 候选人在一个对公共卫生日益重要的领域向独立研究生涯的过渡。

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.