Cardiac Autonomic Function, Cognitive Performance, and Neurocognitive Outcomes

心脏自主功能、认知表现和神经认知结果

• 批准号: 10615166
• 负责人: Christopher Schaich
• 金额: $ 9.71万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615166
• 关键词: Adult; Affect; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Area; Arrhythmia; Atherosclerosis Risk in Communities; Autonomic Dysfunction; Biological Markers; Blood Vessels; Brain region; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Disorders; Cerebrum; Cessation of life; Clinical; Cognition; Cognitive; Cohort Studies; Data; Dementia; Development; Devices; Disease Outcome; Diurnal Rhythm; Education; Elderly; Electrocardiogram; Etiology; Event; Future; Goals; Heart; Heart failure; Hour; Impaired cognition; Impairment; Incidence; Infarction; Intervention; K-Series Research Career Programs; Knowledge; Lacunar Infarctions; Language; Link; Literature; Longitudinal Studies; Measures; Memory; Mentored Research Scientist Development Award; Mentors; Methods; Morbidity - disease rate; Neurocognitive; Neurologic; Neurosciences; Outcome; Parents; Participant; Performance; Perfusion; Periodicity; Persons; Prefrontal Cortex; Prevalence; Prevention strategy; Public Health; Research; Research Project Grants; Resources; Risk; Risk Factors; Role; Signal Transduction; Technology; Training; Vascular Diseases; Ventricular; White Matter Hyperintensity; Work; age related; aging brain; analytical tool; brain health; brain volume; burden of illness; cardiovascular disorder risk; cardiovascular health; career; cerebral microbleeds; circadian; cognitive function; cognitive performance; cognitive testing; cohort; dementia risk; executive function; experience; heart rate variability; indexing; innovation; insight; mild cognitive impairment; mortality; neuroimaging; neuroimaging marker; novel; phenotypic data; population based; signal processing; skills; tool; translational study; treatment strategy; vascular contributions; vascular risk factor; wearable device

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.

项目概要 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，全世界的患病人数将增加两倍。对其病因的了解不足阻碍了进展 一些证据表明心血管疾病。 (CVD) 和各种 CVD 危险因素与血管性危险因素的发生密切相关。 很容易识别并且通常可以改变，因此，发现CVD之前的血管危险因素。 认知障碍或下降将显着增强我们对血管病因的理解 ADRD。源自心电图 (ECG) 的心率变异性 (HRV) 和 QT 间期变异性 (QTV)。 分析显示，这些指标是众所周知的心脏自主控制指标，表明较低的 HRV 和较高的 QTV。 心脏自主神经功能较差，强烈预测未来的心血管发病率和死亡率。 值得注意的是，ADRD 和轻度认知障碍 (MCI) 患者的 HRV 和 QT 异常较低。 因此，HRV 和 QTV 的研究可能为了解心脏自主功能在心脏疾病中的作用提供有价值的见解。 然而，在大多数研究中，HRV 和 QTV 源自标准短期心电图。 （持续时间从 10 秒到几分钟不等），由于 尽管 Zio XT Patch 等可穿戴设备允许最多记录 14 条心电图。 天持续时间，用于分析 HRV 和 QTV 的方法基于平稳性假设，导致 当应用于此类超长期记录时，这些措施可能无法解释或产生误导。 需要创新的信号分析工具来充分利用这些心电图的潜力。最近，出现了一种新信号。 专门开发了一种处理方法，用于从超长期中导出 HRV 和 QTV 的新测量方法 更好地代表现实环境中心脏自主功能的心电图 K01 的主要目标。 受指导的职业发展奖是为了在一个庞大的、持续的群体中实施这种创新的分析工具 对老年人的研究，从最近收集的 14 天 Zio 补丁中得出 HRV 和 QTV 的新测量方法 在目标 1 中，我们将评估这些新措施与认知表现和记录的关联。 在目标 2 中，我们将确定其昼夜变化是否与相关。 最后，我们将利用最近的神经影像学数据来评估认知能力较差或罹患轻度认知障碍 (MCI) 或痴呆症的风险。 一部分参与者以确定超长期 HRV 或 QTV 是否与神经影像学相关 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 ADRD 或脑血管疾病的深入了解。 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功能 此外，该 K01 奖项将提供支持所需的资源。 候选人在公共卫生重要性日益提高的领域转向独立研究职业。

项目成果

Association of Active Renin Content With Mortality in Critically Ill Patients: A Post hoc Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) Trial.

活性肾素含量与危重患者死亡率的关联：脓毒症中维生素 C、硫胺素和类固醇 (VICTAS) 试验的事后分析。

• 发表时间: 2024-03-01
• 影响因子: 8.8
• 作者: Busse, Laurence W;Schaich, Christopher L;Chappell, Mark C;McCurdy, Michael T;Staples, Erin M;Ten Lohuis, Caitlin C;Hinson, Jeremiah S;Sevransky, Jonathan E;Rothman, Richard E;Wright, David W;Martin, Greg S;Khanna, Ashish K;Vitamin C, Thiamine
• 通讯作者: Vitamin C, Thiamine