Aerobic Exercise for Optimizing Cognitive and Brain Health In Remitted Late-Life Depression

摘要 晚年抑郁症(LLD)增加了老年期间许多健康状况不佳的风险，包括医学上的 多种疾病、残疾和死亡。重要的是，LLD还使患痴呆症的风险比 人口普遍老龄化。选定的认知领域(即执行功能)的损害即使在 LLD患者抑郁症状的缓解。改变生活方式是目前最有前途的非 延缓衰老和预防痴呆症认知功能衰退的药理学方法尚未得到应用 用于治疗缓解性LLD(RLLD)的认知障碍。有氧运动(AE)是一种生活方式因素 增强认知功能，对执行功能有明显的好处。声发射也影响着 对执行和记忆功能至关重要的区域和网络中的大脑健康的神经成像标记物(即， 前额叶皮质、海马体、默认模式网络)。至关重要的是，声发射的目标是认知域和大脑 显示LLD最严重和最持久异常的区域和网络。 拟议研究的目标是进行一项方法学上严格的AE试验，使用 用神经成像和神经心理学方法评估AE训练对靶系统的潜在作用 脑异常和2)认知障碍；以及3)探索AE对神经成像的影响程度 大脑健康的标志与rLLD患者的认知益处有关。根据NIMH 实验治疗方法，本项目提出了一项为期6个月的随机对照试验 将中等强度的AE与社交参与度(SE)进行比较，以检查AE的程度 训练影响rLLD患者观察到的结构和功能上的全身性脑异常。这个 第二项研究的目的是探讨声发射训练对rLLD患者认知功能的直接影响。这就做 同时探讨癫痫相关脑改变与认知改善的关系，以探查神经 认知障碍患者声发射影响认知功能的机制通过该奖项提供的培训将包括 1)培养以实验室和家庭为基础的老年病解释性运动干预的专业知识 精神科人群；学习2)先进的7T神经成像数据分析方法和3)纵向 统计分析方法。 总之，这项K23研究是探索认知的生物学机制的第一步。 用实验治疗学方法治疗rLLD患者的AE效果。这样做的结果 研究将提供必要的初步数据，以支持PI努力成为独立的 老年行为健康临床翻译调查员。

ABSTRACT Late-life depression (LLD) increases risk for numerous poor health outcomes in aging, including medical multi-morbidities, disability, and mortality. Importantly, LLD also doubles the risk for dementia relative to the general aging population. Impairment in select cognitive domains (i.e., executive function) persists even after remission of depressive symptoms in LLD. Lifestyle modification is currently the most promising non- pharmacological approach for attenuating cognitive decline in aging and preventing dementia, yet has not been used to target cognitive impairment in remitted LLD (rLLD). Aerobic exercise (AE) is a lifestyle factor that enhances cognitive functioning, with pronounced benefits for executive functioning. AE also influences neuroimaging markers of brain health in regions and networks critical for executive and memory function (i.e., prefrontal cortex, hippocampus, default-mode network). Critically, AE targets cognitive domains and brain regions and networks showing the greatest and most persistent abnormalities in LLD. The goal of the proposed study is to conduct a methodologically rigorous AE trial using comprehensive neuroimaging and neuropsychological approaches to assess the potential of AE training to 1) target systemic brain abnormalities and 2) cognitive deficits; and 3) to explore the extent to which AE effects on neuroimaging markers of brain health relate to its cognitive benefits in those with rLLD. In accordance with the NIMH Experimental Therapeutics approach, this project proposes a 6-month randomized controlled trial comparing moderate-intensity AE to a social engagement (SE) comparison condition, to examine the extent to which AE training influences structural and functional systemic brain abnormalities observed in those with rLLD. The secondary study aim is to examine the direct effect of AE training on cognitive function in those with rLLD. I will also explore the relationship between AE-related brain changes and cognitive improvements to probe neural mechanisms of AE effects on cognition in those with rLLD. The training provided through this award will include 1) building expertise in conducting laboratory- and home-based explanatory exercise interventions in geriatric psychiatric populations; and learning 2) advanced 7T neuroimaging data analytic methods and 3) longitudinal statistical analytic methods. In summary, this K23 study is the first step toward exploring biological mechanisms of the cognitive remediating effects of AE in those with rLLD using an experimental therapeutics approach. The results of this study will provide the necessary preliminary data to support the PI in her efforts to become an independent clinical translational investigator in geriatric behavioral health.