Depression in dementia caregivers: Linking brain structure and sleep-wake risks

痴呆症护理人员的抑郁症：将大脑结构与睡眠-觉醒风险联系起来

基本信息

批准号：
10094254
负责人：
Stephen F Smagula
金额：
$ 10.86万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-08 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10094254
关键词：
Activity Cycles Affect Aging Animals Area Atrophic Behavior Behavioral Blood Pressure Brain Caring Cessation of life Characteristics Chronic Disease Circadian desynchrony Clinical Clinical Research Data Dementia Dementia caregivers Diffuse Disease Progression Early Diagnosis Elderly Epidemiology Ethics Etiology Functional disorder Future Goals Health Health Care Costs Hour Human Immunologics Impairment Inflammatory Interdisciplinary Study Knowledge Lead Link Literature Longitudinal Studies Magnetic Resonance Imaging Measures Medicine Mental Depression Mentors Microvascular Dysfunction Modeling Neuroanatomy Neurobiology Neurosciences Outcome Pathogenesis Pathologic Pathology Pattern Prevention approach Prevention strategy Prospective Studies Provider Public Health Quality of life Reporting Research Research Training Rest Risk Risk Factors Science Scientist Severities Sleep Sleep Deprivation Sleep Fragmentations Sleep Wake Cycle Sleep disturbances Structure Subgroup System Technical Expertise Testing Thick Time Training Vascular Diseases Ventricular Visceral Visit aging brain base career development caregiver strain caregiving cerebral atrophy dementia care depression prevention depressive symptoms disability experience follow-up geriatric depression gray matter high risk multidisciplinary multimodality neuroimaging novel poor sleep prevent programs prospective psychosocial research study skills skills training sleep pattern sleep quality tool white matter white matter damage

项目摘要

Abstract There is a great need to integrate neuroscientific tools into the study of late-life depression (LLD) etiology. My goal is to develop evidence that will help target prevention strategies to the neurobiological basis of LLD vulnerability. Several existing studies demonstrate that LLD pathophysiology is characterized a high burden of structural magnetic resonance imaging (sMRI) measured small vessel disease, white matter damage, and atrophy in key networks, such as those subserving executive and central visceral controls. To build on and extend current literature, there is a need to clarify the specific structural alterations involved in LLD pathogenesis. There is also a fundamental need for evidence regarding the preventable risk factors for pathological brain structural aging. The conceptual model that underlies my research program proposes that 24-hour sleep-wake activity disturbances are a key and understudied risk factor for the specific brain structural alterations that increase LLD risk. To lead future studies that will programmatically advance the neuroscience of depression prevention, I need to build on my past training in risk factor epidemiology and LLD neurobiology in several areas. First, I need clinical research training in the science of depression prevention for high risk older adults, such as dementia caregivers. Second, I must prepare myself to lead multi-modal, longitudinal neuroimaging studies. Third, I must prepare myself to lead studies assessing and interpreting the health relevance of 24-hour sleep-wake activity measures. Therefore, this K01 will provide me with: (1) A capstone field training experience administering ethical, multidisciplinary clinical research studies with older adults who are at high risk for developing depression, plus mentor-guided training in current LLD prevention approaches and the psychosocial/behavioral basis for LLD in at-risk groups; (2) New technical skills collecting, processing, analyzing, and interpreting multi-modal neuroimaging data, plus formal coursework in neuroanatomy/systems neurobiology, and (3) New technical skills measuring and processing 24-hour sleep-wake activity measures, plus grounding in clinical sleep medicine to interpret these metrics. To accomplish these training goals and advance public health relevant knowledge regarding LLD etiology, I propose to longitudinally study changes in depression among older informal dementia caregivers who are experiencing strain delivering care. This group is increasingly public health relevant and at very high risk for depression. Our preliminary data indicates that LLD in strained dementia caregivers may be due to disrupted brain structural connectivity. Longitudinal neuroimaging studies in this group are needed to extend our preliminary findings by evaluating whether/which specific brain structural characteristics predict future increases in the burden of depression. In addition, dementia caregivers often have inadequate sleep and restricted daytime activity, which are both depression risk factors that may increase the rate of brain structural aging (e.g., by activating pro-inflammatory cascades or contributing to vascular disease). I therefore propose a prospective study (n=90) with state-of-the-art 7- Tesla sMRI and actigraphic sleep-wake activity measures repeated at an initial visit and an 18-month follow- up. This will enable me to test and refine a model wherein specific sleep-wake activity disturbances are associated with brain structural changes affecting the key networks underlying LLD risk. The scientific and career development outcomes will be: (1) identification of the specific brain structural networks and sleep-wake activity patterns that predict increases in depression symptom severity among dementia caregivers, (2) refinement of a model linking specific sleep-wake activity characteristics with both pathological brain structural aging and depression symptoms, and (3) a multidisciplinary research scientist with the knowledge, skills, and data needed to develop a confirmatory study (R01) supporting neurobiologically-informed prevention strategies for LLD.

抽象的非常需要将神经科学工具整合到晚年抑郁症（LLD）病因学的研究中。我的目标是开发证据，帮助针对 LLD 的神经生物学基础制定预防策略脆弱性。一些现有的研究表明，LLD 病理生理学的特点是高负担结构磁共振成像 (sMRI) 测量小血管疾病、白质损伤和关键网络萎缩，例如那些支持执行和中央内脏控制的网络。建立在和扩展现有文献，有必要澄清LLD涉及的具体结构改变发病。还根本需要有关可预防风险因素的证据病理性脑结构老化。我的研究计划的概念模型表明 24 小时睡眠-觉醒活动障碍是特定大脑结构的一个关键且尚未得到充分研究的危险因素。增加 LLD 风险的改变。领导未来的研究，以编程方式推进神经科学关于预防抑郁症，我需要以过去在危险因素流行病学和 LLD 神经生物学方面的培训为基础在几个领域。首先，我需要高风险抑郁症预防科学方面的临床研究培训老年人，例如痴呆症护理人员。其次，我必须做好领导多模式、纵向的准备。神经影像学研究。第三，我必须准备好领导评估和解释健康状况的研究 24 小时睡眠-觉醒活动测量的相关性。因此，这个K01将为我提供：（1）一个顶点对老年人进行伦理、多学科临床研究的现场培训经验患有抑郁症的高风险，加上当前 LLD 预防方法的导师指导培训以及高危人群 LLD 的社会心理/行为基础； (2)新技术技能收集、加工、分析和解释多模式神经影像数据，以及神经解剖学/系统的正式课程神经生物学，以及 (3) 测量和处理 24 小时睡眠觉醒活动测量的新技术技能，加上临床睡眠医学的基础来解释这些指标。为了实现这些培训目标并推进有关 LLD 病因学的公共卫生相关知识，我建议纵向研究老年非正式痴呆症护理人员在护理过程中遇到压力，出现抑郁症。本组与公共卫生的关系日益密切，并且患抑郁症的风险非常高。我们的初步数据表明紧张的痴呆症护理人员的 LLD 可能是由于大脑结构连接中断造成的。纵向需要对这一组进行神经影像学研究，通过评估是否/哪些来扩展我们的初步发现特定的大脑结构特征预示着未来抑郁症负担的增加。此外，痴呆症护理人员经常睡眠不足和白天活动受限，这都是抑郁症可能增加大脑结构老化速度的危险因素（例如，通过激活促炎级联反应或导致血管疾病）。因此，我提出一项前瞻性研究（n=90），采用最先进的 7- Tesla sMRI 和活动记录睡眠-觉醒活动测量在初次就诊和 18 个月的随访中重复进行向上。这将使我能够测试和完善一个模型，其中特定的睡眠-觉醒活动干扰是与影响 LLD 风险的关键网络的大脑结构变化相关。科学和职业发展成果将是：（1）识别特定的大脑结构网络和睡眠-觉醒预测痴呆症护理人员抑郁症状严重程度增加的活动模式，(2) 完善将特定睡眠-觉醒活动特征与病理性大脑结构联系起来的模型衰老和抑郁症状，以及 (3) 具有知识、技能和能力的多学科研究科学家开发支持神经生物学预防策略的验证性研究 (R01) 所需的数据对于LLD。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Engaging Early-Career Geriatric Mental Health Investigators as Associate Editorial Board Members.

聘请早期职业生涯老年心理健康调查人员作为副编辑委员会成员。

DOI：
发表时间：
2017-04
期刊：
影响因子：
0
作者：
Simning, Adam;Smagula, Stephen F
通讯作者：
Smagula, Stephen F

Initial evidence regarding the neurobiological basis of psychological symptoms in dementia caregivers.

关于痴呆症护理人员心理症状的神经生物学基础的初步证据。

DOI：
发表时间：
2023-05-18
期刊：
影响因子：
6.8
作者：
Smagula, Stephen F;Aizenstein, Howard J
通讯作者：
Aizenstein, Howard J

Cancer Bereavement and Depression Symptoms in Older Spouses: The Possible Modifying Role of the Circadian Rest-Activity Rhythm.

老年配偶的癌症丧亲和抑郁症状：昼夜休息活动节律的可能改变作用。

DOI：
发表时间：
2021-03
期刊：
影响因子：
2.8
作者：
Stahl, Sarah T;Neagoe, Ioana;Smagula, Stephen F;Posluszny, Donna;Bovbjerg, Dana H
通讯作者：
Bovbjerg, Dana H

Timing of Daily Activities over a 24-Hour Period and Affective Status among a National Cohort of Older Dementia Caregivers.

全国老年痴呆症护理人员群体 24 小时内的日常活动时间安排和情感状态。

DOI：
发表时间：
2021
期刊：
影响因子：
2.8
作者：
Stahl, Sarah T;Rodakowski, Juleen;Smagula, Stephen F
通讯作者：
Smagula, Stephen F

Moderators of Response to Cognitive Behavior Therapy for Major Depression in Patients With Heart Failure.

心力衰竭患者重度抑郁症认知行为治疗反应的调节因素。

DOI：
发表时间：
2019
期刊：
影响因子：
3.3
作者：
Smagula, Stephen F;Freedland, Kenneth E;Steinmeyer, Brian C;Wallace, Meredith J;Carney, Robert M;Rich, Michael W
通讯作者：
Rich, Michael W