Aerobic Exercise for Optimizing Cognitive and Brain Health in Remitted Late-Life Depression
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Change from baseline in Cardiovascular Fitness at 6 months
研究概览
简要总结
Cognitive impairment and brain abnormalities are common and persist after depression remission in those with Late Life Depression (LLD), compounding dementia risk in both individuals with acute and remitted LLD (rLLD). In this study, investigators will examine systemic neural and cognitive benefits of aerobic exercise training in older adults with remitted LLD. This will generate preliminary data regarding neural targets of aerobic exercise training that may translate to cognitive benefits in those with rLLD, a population who remains at high risk for dementia despite successful treatment of depression.
详细描述
Significance:
The population of adults aged >65 years in United States is expected to nearly double between 2012 and 2050, with a projected estimate of 83.7 million adults aged >65 years by 2050. The prevalence of depressive symptoms among older adults ranges 15 - 27% in the community and up to 37% in primary care settings. Though subclinical depressive symptoms are more prevalent than Major Depression (MDD) among older adults (MDD: 5.5% prevalence), rates of MDD in older people have been rising over the past two decades. Late-life depression (LLD) results in enormous economic, public health, and caregiver burden. This high economic cost consists of both direct and indirect costs (e.g., increased use of medical resources, need for unpaid family caregiving). Further, LLD exacerbates chronic medical illness burden and confers the greatest risk for mortality across all mental health conditions in aging. LLD also increases disability risk, with one report estimating 79% of LLD having functional limitations. Importantly, those with LLD are at a twofold increased risk for dementia relative to the general aging population, which has catastrophic implications for the long-term economic and public health burden of LLD.
Background:
Older adults with LLD are particularly predisposed to accelerated rates of cognitive decline and progression to dementia. While nearly half of those with LLD have significant cognitive impairment, cognitive deficits are inadequately addressed using conventional antidepressant treatments. Exercise has emerged as the leading non-pharmacological approach to improve cognition and reduce dementia risk in aging. AE interventions in older adults, over as short as 6-months, have been shown to improve performance in cognitive functions (i.e., executive function) and brain regions and networks (i.e., PFC, HC, DMN) that are most sensitive to the neurotoxic effects of LLD. However, our knowledge of AE-related cognitive and brain changes in aging are primarily drawn from AE trials conducted in populations at low risk for dementia. Though an emerging literature supports the benefits of AE for cognitive and brain health in those with MCI, these studies systemically exclude psychiatric populations. By excluding those with LLD, existing studies are overlooking a subsample of older adults at ultra-high risk for dementia for whom the cognitive and neural benefits of AE training may be particularly consequential. This necessitates a better understanding of the potential of AE training to target systemic brain features and cognition in those who have had LLD.
Impact:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 60+ years
- •Major Depressive Episode in older adulthood (since age 55)
- •Current level of depressive symptoms does not meet criteria for a Major Depressive Episode
- •Ambulatory without pain or the assistance of walking devices
- •Able to speak and read English
- •Exercise level of <100 minutes per week on average
- •Medical clearance by primary care physician (PCP)
- •Living in community for duration of the study
- •Reliable means of transportation
- •No diagnosis of a neurological disease
- •Eligible to undergo MRI
排除标准
- •Current diagnosis of a Major Depressive Episode
- •Significant suicide risk (i.e., current, active suicidal ideation with a plan)
- •Electroconvulsive therapy within the past 12 months
- •Engaging in moderate-intensity exercise >100 minutes per week on average
- •Current treatment for cancer - except non-melanoma skin
- •Neurological condition (MS, Parkinson's, Dementia, MCI) or brain injury (Stroke)
- •Substance Use disorder in the past 3-months
- •Current treatment for congestive heart failure, angina, uncontrolled arrhythmia, deep vein thromboses (DVT) or other cardiovascular event
- •Myocardial infarction, coronary artery bypass grafting, angioplasty or other cardiac condition in the past year including uncontrolled hypertension
- •Regular use of an assisted walking device
- •Presence of metal implants (pacemaker, stents) that would be MR ineligible
- •Claustrophobia
- •Color Blindness
- •Significant visual or hearing impairments that would preclude neuropsychological assessment or communication with study staff via a virtual format (videoteleconference)
- •Not fluent in English
- •Not medically cleared by PCP
- •Traveling consecutively for 3+ weeks during the study
- •MOCA (<20 to exclude) and MADRS (>9 to exclude)
结局指标
主要结局
Change from baseline in Cardiovascular Fitness at 6 months
时间窗: Baseline and 6-months
Cardiorespiratory fitness will be measured via a cardiopulmonary exercise test (CPET) indicated by maximal VO2 on a motorized treadmill. while measuring oxygen utilization via Parvo Medics True one metabolic cart. The test follows a modified Balke protocol in which speed remains constant with the intensity being increased every two minutes via a raise of 2.0% of the incline. The speed was an agreed upon speed between participant and staff (between 2.0 and 4.0 mph). The test will conclude when the participant reaches 85% of age predicted maximal heart rate, rating of perceived exertion (RPE) equal to or greater than 15 for those who have blunted heart rate response due to beta block medication, or volitional termination by participant.
Depressive Symptoms
时间窗: Continuously up to every 6-weeks for 6 months
For the frequent assessment of depressive symptoms during the intervention while minimizing participant and clinician burden, the Patient Health Questionnaire-9 item version (PHQ-9; score ranges from 0 \[better\] to 27 \[worse\]), a self-report questionnaire, will be administered.
Changes from baseline in Brain Structure and Function at 6 months
时间窗: Baseline and 6-months
Brain imaging conducted with a 7 Tesla scanner. Of particular interest are changes in hippocampal volume. This measurement is reported in mm\^3, with higher numbers indicating higher levels of gray matter in the hippocampal region. Changes in prefrontal cortical thickness are also of interest, measured in mm. Brain functional network changes of interest are changes in intra- and inter-connectivity of the default-mode and executive control large-scale brain networks.
Changes from baseline in depressive symptoms at 6 months
时间窗: Baseline and 6-months
Given that all participants will have a recent history of depression, and may have lingering low level symptoms or may even relapse, depressive symptoms will be assessed using the Montgomery Asberg Depression Rating Scale (MADR; score ranges from 0 \[better\] to 60 \[worse\]), a clinician administered measure of depression severity.
Change from baseline in Cognitive Function at 6 months
时间窗: Baseline and 6-months
Assessed with a comprehensive Neuropsychological Battery. The primary cognitive outcome will be assessed using a composite score (mean) of standardized scores (Z-scores) from the following executive functioning tests from the NIH toolbox: 1) Dimensional Change Card Sort Test (set-shifting), Flanker Inhibitory Control and Attention Test (inhibition), List Sorting Working Memory Test (working memory).
次要结局
- Changes from baseline in intensity of physical activity at 6 months(Baseline and 6-months)
- Change from baseline in amount of physical activity at 6 months(Baseline and 6-months)
- During-intervention physical activity levels(Continuously up to every 2 months for 6 months)
- Change from baseline in Subjective Cognitive Function at 6 months(Baseline and 6-months)
研究者
Swathi Gujral
Assistant Professor of the Department of Psychiatry at the University of Pittsburgh, School of Medicine
University of Pittsburgh