Determinants of Altered Brain Structure and Function in Smokers With COPD-Related Lung Pathophysiology
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- Neuropsychological test performance: average executive functioning-processing speed domain summary score
研究概览
简要总结
COPD is the third leading cause of combined morbidity, disability, and mortality in the United States and is often associated with cognitive impairment. The goal of the proposed project is to examine novel pulmonary and vascular physiological mechanisms that contribute to structural brain abnormalities and cognitive dysfunction early in the course of COPD. The project will generate information to ultimately inform the development of interventions to delay or prevent cognitive dysfunction.
详细描述
Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of morbidity and mortality in the US with increasing prevalence in older adults. The impact of COPD on the brain is an area of expanding research interest. A staggering 40-60% of patients with COPD have cognitive impairments including deficits in executive functioning (e.g., decision making), processing speed, and memory. Intact cognition is critical for independently managing daily tasks (e.g., medication and money management). Since there are currently no treatments to fully reverse cognitive impairment once it is present, preventing and delaying onset is essential. Given the high prevalence of COPD, understanding how COPD confers an increased risk for cognitive impairment should be a top public health priority. There is an urgent need to identify potentially modifiable physiological characteristics of individuals with early COPD-related pathophysiology who are at risk of developing brain abnormalities. The earliest changes that occur in COPD are driven by an enhanced chronic inflammatory response that includes small airway disease in the lung and vascular abnormalities. COPD-related lung pathophysiology can be measured continuously and is separable from amount of smoking. These physiological changes are often present in individuals who do not meet traditional criteria for COPD diagnosis and have not yet manifested significant clinical symptoms. We propose that chronic smokers who are susceptible to COPD and show evidence of COPD-related lung pathophysiology on lung CT also experience vascular dysfunction (particularly central artery stiffness) that contributes to structural brain abnormalities and cognitive impairment. The proposed project will: 1) model the effects of novel physiological mechanisms on the brain in COPD, 2) focus on changes in brain structure and function early in the development of COPD by including smokers who have evidence of early COPD-related lung pathophysiology but do not meet traditional criteria for COPD, and 3) utilize advanced technology to assess the lung (lung CT) and brain (MRI). We will recruit participants with existing lung CT from ongoing NIH projects to complete pulmonary and vascular measures, cognitive assessment, and brain MRI. The project is highly multidisciplinary and leverages unique resources at the University of Iowa including the Institute for Clinical and Translational Science, the Translational Human Vascular Physiology Lab, the Iowa Neuroimaging Consortium, and the Iowa Comprehensive Lung Imaging Center.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 30 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 30-85, > 8th grade education, Normal/corrected hearing and vision, English Speaker, Ability to comfortably lie flat for 1 hour.
排除标准
- •Other concomitant respiratory disorder other than asthma (e.g., cystic fibrosis), Use of antibiotics or steroids for a COPD exacerbation within the past month, Use of 24-hour oxygen, Pregnancy or suspected pregnancy, Uncontrolled cancer within the last 5 years, Radiation therapy to the chest, Lung surgery (LVRS, transplant, lobectomy), Lung cancer known or suspected, Eye surgery in the last 3 months, Pulmonary Hypertension, Insulin-dependent diabetes, Inability to use albuterol, Chest or abdominal surgery in the past 3 months, Heart attack in the last 3 months, Hospitalization for any heart problem in the past month, Prior neurological condition (e.g., stroke, epilepsy, head injury with >15 mins. loss of consciousness), Previous diagnosis of dementia or learning disability, Major comorbid medical conditions with known cognitive effects (e.g., renal failure, HF), Psychotic disorder, bipolar disorder, current substance use disorder other than tobacco use, Change in psychiatric medication in last month, Claustrophobia, Metal object in body that may interfere with neuroimaging.
研究组 & 干预措施
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Neuropsychological Assessment (Behavioral)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Spirometry (Procedure)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Arterial Blood Gas (Procedure)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Diffusion Capacity of the Lung for Carbon Monoxide (Procedure)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: 6 Minute Walk Test (Diagnostic Test)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Systemic Vascular Measures (Procedure)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Blood Biomarkers (Biological)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Symptom Questionnaire Measures (Behavioral)
Never Smoker
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Brain MRI (Procedure)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Neuropsychological Assessment (Behavioral)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Spirometry (Procedure)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Arterial Blood Gas (Procedure)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Diffusion Capacity of the Lung for Carbon Monoxide (Procedure)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: 6 Minute Walk Test (Diagnostic Test)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Systemic Vascular Measures (Procedure)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Blood Biomarkers (Biological)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Symptom Questionnaire Measures (Behavioral)
Smoker/Past smoker-No Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Brain MRI (Procedure)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Neuropsychological Assessment (Behavioral)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Spirometry (Procedure)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Arterial Blood Gas (Procedure)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Diffusion Capacity of the Lung for Carbon Monoxide (Procedure)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: 6 Minute Walk Test (Diagnostic Test)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Systemic Vascular Measures (Procedure)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Blood Biomarkers (Biological)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Symptom Questionnaire Measures (Behavioral)
Smoker/Past smoker-W/Airflow Limitation
Neuropsychological Assessment, Spirometry, Arterial Blood Gas, Diffusion Capacity of the Lung for Carbon Monoxide, 6 Minute Walk test, Systemic Vascular Measures, Blood Biomarkers, Symptom Questionnaire Measures, Brain MRI
干预措施: Brain MRI (Procedure)
结局指标
主要结局
Neuropsychological test performance: average executive functioning-processing speed domain summary score
时间窗: At the end of data collection in 2024
The domain summary score represents the average of the norm referenced standardized scores for the following measures: Trail Making Test Part B, Controlled Oral Word Association, Stroop Color Word Test Interference Score, and WAIS-IV (Wechsler Adult Intelligence Scale IV) Coding
White matter (WM) structural integrity from brain magnetic resonance imaging (MRI)
时间窗: At the end of data collection in 2024
Fractional anisotropy from diffusion weighted imaging will be the primary WM measure
次要结局
未报告次要终点
研究者
Karin Hoth
Professor
University of Iowa