Phenotype Predictors of Cognitive Outcomes in Geriatric Depression
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- Cognitive clinical diagnosis
研究概览
简要总结
This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.
详细描述
In this renewal of R01MH108578, the investigators are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which the investigators have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN).
The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, the study will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year functional brain magnetic resonance imaging (fMRI) scan.
In this renewal, the investigators will examine the following specific aims:
- To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD).
- To study effects of stress and neuroticism on brain structure and function in older adults with MDD history.
- To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •major depression, single episode or recurrent;
- •ability to read and write English;
- •Mini-Mental State Examination >25.
排除标准
- •lifetime alcohol/drug dependence
- •conditions associated with brain abnormalities such hydrocephalus, benign and cancerous brain tumors, epilepsy, Parkinson's disease, Huntington's chorea, dementia, demyelinating diseases, etc.
- •untreated endocrine disorder other than diabetes mellitus
- •established clinical diagnosis of dementia
- •other primary psychiatric disorders, e.g., panic disorder, social phobia, obsessive- compulsive disorder, schizoaffective disorder, schizophrenia, bipolar disorder
研究组 & 干预措施
Depressed
Subjects receive FDA-approved antidepressants
干预措施: Sertraline, bupropion, desvenlafaxine (Drug)
结局指标
主要结局
Cognitive clinical diagnosis
时间窗: three years
Participant records will be reviewed annually by the consensus panel. The study will convene a panel of experts to review each case, including the PI, treating geriatric psychiatrists and study neuropsychologist. Panel members review the following information for each participant: 1) initial evaluation and most recent clinical depression study notes, 2) neuropsychological testing profiles, 3) informant report of cognitive decline based on the Dementia Severity Rating Scale, 4) study structural MRI images to determine vascular burden, and 5) additional neurological and clinical neuropsychological consultations when available. The panel discusses the case until a consensus cognitive diagnosis is reached.
Montgomery-Asberg Depression Rating Scale (MADRAS)
时间窗: Three years
Measure of depression severity and Recurrence of Depression Minimum Score = 0; Maximum Score = 60; Higher score means worse outcome
Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Battery Total Score
时间窗: Three years
Global cognitive measure; Minimum Score = 0; Maximum Score = 100; Higher score means better outcome
次要结局
- Functional brain magnetic resonance imaging (fMRI) scan structural imaging changes(Two years)
- Functional brain magnetic resonance imaging (fMRI) scan changes in resting state functional connectivity.(Two years)
研究者
David Steffens
Samuel "Sy" Birnbaum/Ida, Louis and Richard Blum Chair in Psychiatry Professor and Chair, Department of Psychiatry
UConn Health