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

摘要 哮喘是一种慢性炎症性气道疾病，患病率不断增加，与哮喘的发生有关。 对患者的生活质量造成巨大负担，对社会造成经济负担。尽管取得了进展， 药物治疗，总体哮喘控制仍然不令人满意，并且治疗不依从性 极高现有的研究，其中大部分是由调查人员对这一建议， 表明哮喘可能与大脑结构和生物化学的变化有关， 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，特别是在中年到老年 患者先前的研究也没有描述认知功能的关键领域之间的关系 以及哮喘特有的大脑结构、化学和功能的可能变化。此外， 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， 药物治疗，气道炎症）在解释哮喘和衰老中的一些缺陷方面还没有得到证实。 探讨了因此，我们建议比较126名40-69岁的成人，诊断为哮喘，并分层 年龄（30岁）和哮喘严重程度，66名年龄匹配的非哮喘对照使用认知测试 包括处理速度、情景记忆和执行功能。参与者还将接受 神经成像结构磁共振成像（MRI）将集中在海马体积。扩散 张量成像（DTI）将用于测量白色物质完整性的完整性，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）。三个功能 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， （B）随后的记忆任务，以评估海马神经元的作用。 激活服务的记忆编码，和（c）调制任务，测量的能力， 认知控制网络，随着任务需求的增加，增加额顶叶区域的大脑活动。我们将 还研究了认知障碍是否是由先前推断的不同大脑变化介导的。 老龄化研究和呼吸系统疾病试点研究。此外，我们还将研究 抑郁情绪，睡眠质量和全身炎症，以及哮喘相关变量在介导 这些协会。我们假设哮喘患者与对照组相比， 大脑老化，表现为认知缺陷和大脑变化，随着年龄的增长， 年龄因此，该建议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。一个多学科研究 团队在哮喘患者的心理健康方面拥有丰富的经验， 寿命将进行研究。

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.