Accelerated Age-related Cognitive Decline: Impact of Exercise on Executive Function and Neuroplasticity (EXEC-study)

与年龄相关的认知能力加速衰退：运动对执行功能和神经可塑性的影响（EXEC 研究）

• 批准号: 10612082
• 负责人: Ulf G Bronas
• 金额: $ 52万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10612082
• 关键词: 3-Dimensional; Acceleration; Address; Adherence; Affect; Age; Age-associated memory impairment; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anisotropy; Atrophic; Attention; Attenuated; Behavior Therapy; Blood Vessels; Brain; Brain region; Caring; Cerebrovascular Circulation; Chronic Kidney Failure; Clinical; Code; Cognition; Cognitive; Communities; Control Groups; Data; Dementia; Diffusion; Digit structure; Disease; Dose; Elderly; Ethnic Origin; Exercise; Functional Magnetic Resonance Imaging; Goals; Health; Hippocampus; Home; Impaired cognition; Institutionalization; Learning; Longevity; Magnetic Resonance Imaging; Measures; Mediation; Medical; Memory; Moderate Exercise; Nerve Degeneration; Neuronal Plasticity; Nonpharmacologic Therapy; Oxidative Stress; Participant; Patients; Perfusion; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pilot Projects; Population; Populations at Risk; Prevalence; Prevention; Process; Randomized; Renal function; Rest; Risk; Severities; Severity of illness; Structure; Testing; Treatment Protocols; Walking; Work; adherence rate; arterial spin labeling; attentional control; behavioral response; blood perfusion; brain behavior; cerebral atrophy; cerebral hypoperfusion; cognitive function; cohort; comorbidity; comparison control; effective therapy; executive function; exercise adherence; exercise program; exercise training; functional decline; illness length; improved; information processing; mild cognitive impairment; morphometry; placebo group; poor health outcome; premature; preservation; prevent; primary outcome; retention rate; sex; side effect; systemic inflammatory response; walking program; white matter

Abstract: Older adults with chronic kidney disease (CKD) present on the spectrum of Alzheimer's Disease and Related Dementias (ADRD) approximately 10 years earlier than age and sex matched controls. The prevalence of accelerated age-related cognitive decline and dementia is remarkably high in older adults with CKD, affecting as many as 20-50%. Cognitive impairment in this population leads to poor health outcomes, decreased medication and medical care adherence, functional decline and an accelerated loss of independence, and premature institutionalization. The accelerated age-related cognitive decline in patients with CKD is due, in part, to the CKD disease process itself, which leads to a reduction in white matter integrity that is superimposed on accelerated neurodegeneration of brain regions including atrophy of the hippocampus. Moreover, reduced kidney function is independently associated with lower cerebral blood flow leading to cerebral hypoperfusion, which further exacerbates cognitive decline. Current treatment regimens for CKD do not include strategies to prevent accelerated cognitive decline and related dementia. The available pharmaceutical therapies to enhance cognition have only modest short-term effects on slowing cognitive impairment, have intolerable side effects, and require dose-reduction in CKD patients. Thus, there is a pressing need to develop non-pharmacological therapies to prevent or forestall cognitive decline in older adults with CKD at risk for ADRD. The objective of this study is to test the hypothesis that a 6-month home-based walking exercise program in 116 older adults with mild cognitive impairment and CKD will improve executive function, cognitive subdomains, brain white matter integrity, structure, and functional connectivity compared to attention control. We will achieve this objective by addressing the following specific aims. 1: Does exercise work? Quantify change in executive cognitive function (primary outcome), and cognitive subdomains. 2. For whom does exercise work? Examine if factors (e.g. age, sex, cognitive impairment, and, comorbid conditions) moderate exercise-induced improvement in cognitive function domains at 6-months. 3. How does exercise work? Using MRI we will quantify change from baseline to 6-months in white matter integrity, functional connectivity, cerebral blood flow and perfusion, and hippocampal volume. We will also evaluate the mediation effects of total exercise volume on cognitive function domains and MRI measures at 6-months. Our long-term goal is to develop community-based, behavioral interventions to prevent age-related cognitive decline and ADRD in at risk populations across the lifespan. This study will address a critical gap in our understanding of the use of exercise in the prevention and treatment of accelerated age-related cognitive decline in older adults with CKD and mild cognitive impairment. By combining cognitive function assessment with MRI, we will be able to evaluate the brain-behavior response to exercise and discern the relationships at a level previously not conducted in this population. The potential clinical impact is high and readily translatable.

抽象的： 老年人患有慢性肾脏疾病（CKD），这是阿尔茨海默氏病及相关的 痴呆症（ADRD）大约比年龄和性别匹配的对照大约10年。流行率 CKD的老年人加速与年龄相关的认知下降和痴呆症相当高，影响 多达20-50％。该人群的认知障碍导致健康结果不佳，下降 药物和医疗保健依从性，功能下降和加速失去独立性，以及 早产制度化。 CKD患者的与年龄相关的认知下降是应造成的 部分，CKD疾病过程本身，这导致白质完整性的降低是 叠加在包括海马萎缩在内的大脑区域的加速神经变性上。 此外，肾功能降低与较低的脑血流独立相关，导致 脑灌注不足，进一步加剧了认知能力下降。 CKD的当前治疗方案 不包括防止加速认知能力下降和相关痴呆症的策略。可用 增强认知的药物疗法仅对降低认知能力有适度的短期影响 损害，具有无法忍受的副作用，需要减少CKD患者的剂量。因此，有一个 迫切需要开发非药物疗法以预防或防止老年人认知能力下降 CKD有ADRD的风险。这项研究的目的是检验一个基于6个月的家庭的假设 116名老年人有轻度认知障碍和CKD的步行锻炼计划将改善执行官 与相比 注意控制。我们将通过解决以下特定目标来实现这一目标。 1：运动 工作？量化执行认知功能（主要结果）和认知子域的变化。 2 运动可以工作？检查因素是否（例如年龄，性别，认知障碍，以及合并症 条件）在6个月时，认知功能域的中等运动引起的改善。 3。怎么样 运动工作？使用MRI，我们将量化从基线到白质完整性6个月的变化， 功能连通性，脑血流和灌注以及海马体积。我们还将评估 总运动体积对6个月时认知功能域和MRI度量的调解作用。我们的 长期目标是制定基于社区的行为干预措施，以防止与年龄相关的认知 整个生命周期的风险人群的衰落和addrd。这项研究将解决我们的关键差距 了解锻炼在预防和治疗加速与年龄有关的认知方面的使用 CKD和轻度认知障碍的老年人的下降。通过结合认知功能评估 使用MRI，我们将能够评估脑行为对运动的反应，并辨别 以前没有在该人群中进行的水平。潜在的临床影响很高且容易翻译。