The Dallas Asthma Brain and Cognition Study (Dallas ABC Study)

达拉斯哮喘大脑和认知研究（达拉斯 ABC 研究）

基本信息

批准号：
10219346
负责人：
E SHERWOOD BROWN
金额：
$ 72.55万
依托单位：
SOUTHERN METHODIST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10219346
关键词：
Adrenal Cortex Hormones Adult Adult asthma Adverse effects Affect Age Aging Airway Disease Asthma Brain Brain imaging Chemistry Chronic Clinical Cognition Cognitive Cognitive deficits Dementia Depression screen Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Elderly Episodic memory Financial Hardship Functional Magnetic Resonance Imaging Future Goals Hippocampus (Brain)Impaired cognition Individual Inflammation Inflammatory Inhalation Inositol Intake Interdisciplinary Study Life Link Longevity Lung diseases Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measures Mediating Mediation Mediator of activation protein Memory Memory impairment Mental Health Moods N-acetylaspartate Nerve Degeneration Neuraxis Neurons Neuropsychological Tests Neuropsychology Outcome Parietal Participant Pathway interactions Patients Performance Pharmaceutical Preparations Pharmacological Treatment Population Prevalence Process Protons Quality of life Reporting Research Research Personnel Rest Risk Role Scanning Services Severities Severity of illness Short-Term Memory Sleep Societies Structural Biochemistry Structural Chemistry Structure Symptoms Time United States age effect age related aged aging brain airway inflammation asthmatic patient biobehavior cognitive ability cognitive control cognitive function cognitive testing dementia risk depressive symptoms economic cost executive function experience functional MRI scan gray matter illness length memory encoding middle age mild cognitive impairment mortality neuroimaging neurophysiology nitrosative stress patient population preventive intervention processing speed relating to nervous system response sleep quality systemic inflammatory response trend white matter

项目摘要

Abstract Asthma is a chronic inflammatory airway disease, with an increasing prevalence, that is associated with a substantial burden on quality of life for patients and financial burden on society. Despite progress in the pharmacological treatment, overall asthma control remains unsatisfactory and treatment non-adherence is extremely high. The available research, much of which was conducted by investigators on this proposal, suggests that asthma may be associated with changes in brain structure and biochemistry, as well as increased risk for cognitive impairment and dementia. However, little is known about the impact of asthma on cognitive function and associated central nervous system processes, especially for in middle- to older age patients. Prior research has also not characterized the relationship between key domains of cognitive function and possible changes in brain structure, chemistry, and function specific to asthma. Additionally, the role of biobehavioral factors (such as mood, sleep, or inflammation) and asthma-specific factors (severity, duration, medication, airway inflammation) in explaining some of these deficits in asthma and aging has not been explored. We therefore propose to compare 126 adults 40-69 years old, diagnosed with asthma, and stratified for age (three decades) and asthma severity, with 66 age-matched non-asthmatic controls using cognitive tests that include processing speed, episodic memory, and executive function. Participants will also undergo neuroimaging. Structural magnetic resonance imaging (MRI) will focus on hippocampal volume. Diffusion tensor imaging (DTI) will be used to measure integrity of white matter integrity, which is associated with processing speed. Proton magnetic resonance spectroscopy (1HMRS) will measure metabolites linked to neuronal degeneration (N-acetyl aspartate, NAA) and glial inflammation (myo-inositol, mI). Three functional MRI scans will measure brain activity under different cognitive conditions: (a) a resting state scan to examine functional connectivity of brain networks; (b) a subsequent memory task to assess the role of hippocampal activation in the service of memory encoding, and (c) a modulation task that measures the ability of the cognitive control network to increase brain activity in fronto-parietal regions as task demands increase. We will also examine whether cognitive impairments are mediated by distinct brain changes extrapolated from prior research on aging and pilot research on respiratory disease. In addition, we will study a potential role of depressive mood, sleep quality and systemic inflammation, as well as asthma-relevant variables in mediating these associations. We hypothesize that asthma patients, compared to controls, will demonstrate accelerated brain aging as demonstrated by cognitive deficits and brain changes, which increase in magnitude with older age. Thus, this proposal will provide fundamental information to develop future preventative and intervention efforts to mitigate the potentially adverse effects of asthma on brain and cognition. A multidisciplinary research team with extensive experience in mental health in asthma patients, as well as neuroimaging across the lifespan will conduct the study.

抽象的哮喘是一种慢性炎症性气道疾病，其患病率不断增加，与给患者的生活质量带来沉重负担，给社会带来经济负担。尽管在这方面取得了进展药物治疗后，总体哮喘控制仍不令人满意，并且治疗不依从性极高。现有的研究，其中大部分是由研究人员针对该提案进行的，表明哮喘可能与大脑结构和生物化学的变化以及认知障碍和痴呆症的风险增加。然而，人们对哮喘的影响知之甚少。认知功能和相关的中枢神经系统过程，尤其是中老年人患者。先前的研究也没有描述认知功能关键领域之间的关系以及哮喘特有的大脑结构、化学和功能可能发生的变化。此外，角色生物行为因素（如情绪、睡眠或炎症）和哮喘特异性因素（严重程度、持续时间、药物、气道炎症）在解释哮喘和衰老中的一些缺陷方面尚未得到证实探索过。因此，我们建议比较 126 名 40-69 岁、被诊断患有哮喘的成年人，并进行分层使用认知测试对 66 名年龄匹配的非哮喘对照者进行年龄（三十岁）和哮喘严重程度分析包括处理速度、情景记忆和执行功能。参与者还将经历神经影像学。结构磁共振成像（MRI）将重点关注海马体积。扩散张量成像（DTI）将用于测量白质完整性的完整性，这与处理速度。质子磁共振波谱 (1HMRS) 将测量与以下物质相关的代谢物神经元变性（N-乙酰天冬氨酸，NAA）和神经胶质炎症（肌醇，mI）。三功能 MRI 扫描将测量不同认知条件下的大脑活动：(a) 静息状态扫描以检查大脑网络的功能连接； (b) 随后的记忆任务来评估海马的作用记忆编码服务中的激活，以及（c）测量记忆编码能力的调制任务随着任务需求的增加，认知控制网络会增加额顶叶区域的大脑活动。我们将还检查认知障碍是否是由先前推断的不同大脑变化介导的衰老研究和呼吸系统疾病试点研究。此外，我们将研究潜在的作用抑郁情绪、睡眠质量和全身炎症，以及与哮喘相关的调节变量这些协会。我们假设哮喘患者与对照组相比，会表现出加速认知缺陷和大脑变化表明大脑老化，随着年龄的增长，认知缺陷和大脑变化的程度会增加年龄。因此，该提案将为制定未来的预防和干预措施提供基本信息努力减轻哮喘对大脑和认知的潜在不利影响。多学科研究团队在哮喘患者心理健康以及神经影像学方面拥有丰富的经验寿命将进行这项研究。