4/5 Neurocognitive and neuroimaging biomarkers: predicting progression towards dementia in late-life depression

4/5 神经认知和神经影像生物标志物：预测晚年抑郁症的痴呆进展

基本信息

批准号：
9755510
负责人：
Helen Lavretsky
金额：
$ 43.01万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2017-09-18 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9755510
关键词：
Address Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease risk American Antidepressive Agents Biological Markers Brain Brain imaging Chronic Clinical Clinical Trials Cognitive Data Dementia Disease remission Education Elderly Enrollment Episodic memory Family Funding Gender Goals Image Impaired cognition Impairment Incidence Individual Inflammatory Infrastructure Intervention Lead Link Long-Term Care Magnetic Resonance Imaging Major Depressive Disorder Medical Memory Loss Mental Depression Modeling Molecular Molecular Profiling Neurocognitive Neurocognitive Deficit Outcome Participant Pathway interactions Patient-Focused Outcomes Peripheral Pharmacotherapy Phenotype Plasma Proteins Population Positioning Attribute Prevalence Preventive care Proteins Public Health Randomized Research Institute Resistance Risk Sample Size Site Structure Suicide Testing Therapeutic Time Vascular Dementia Work base care costs cognitive function cognitive performance cortico-limbic circuits cost dementia risk depressive symptoms design effective therapy executive function experience geriatric depression high risk high risk population improved indexing innovation learning strategy molecular marker neural circuit neuroimaging neuroimaging marker novel older patient persistent symptom predictive marker predictive tools prevent recruit relating to nervous system senescence treatment response

项目摘要

PROJECT SUMMARY DESCRIPTION: Dementia, especially Alzheimer's dementia (AD), is a growing public health problem with a prevalence of 5M in the US alone (33M worldwide). Despite a decrease in incidence rates, with the aging of the population, the prevalence of dementia is expected to increase to 16M in the US (115M worldwide) with associated costs rising to $1T. Delaying long-term care by 1 month for older Americans would save $60B annually in direct care cost. Efforts to prevent or delay dementia have been largely unsuccessful. However, major depressive disorder in late life (“late-life depression”, LLD) has been identified as one of six treatable risk factors for dementia, especially AD and vascular dementia. The depression-dementia relationship may be magnified in elders who do not respond to antidepressant treatment and experience persistent symptoms. Thus, resolving whether those with treatment-resistant late-life depression (TRLLD) are at higher risk of cognitive decline and progression to dementia compared to those with treatment-responsive LLD is critically important. Leveraging a Patient-Centered Outcomes Research Institute (PCORI)-funded treatment study of N=1500 people with LLD, across 5 sites, we propose to comprehensively delineate neurocognitive and neuroimaging biomarkers associated with progression to dementia in people with persistent LLD (i.e., TRLLD) compared to those whose LLD remits with treatment. We anticipate enrolling 750 elders with LLD and characterizing their symptomatic trajectory over 24 months. We will assess each participant at three time points with neurocognitive and advanced neuroimaging. We hypothesize that changes in executive functions and the executive control network, as well as changes in episodic memory and the default mode/cortico-limbic network, will be greater in those with TRLLD than in those who respond to treatment and stay well. We also hypothesize that changes over two years in executive function and episodic memory will be specifically associated with changes in executive- control and cortico-limbic circuitry, respectively. Based on our recent findings that inflammatory and related molecular markers can differentiate those with neurocognitive impairment and LLD from those with LLD alone, we will build a predictive multivariate model combining baseline neurocognitive, neuroimaging, and plasma protein data to determine who is at greatest risk for cognitive decline and dementia. Finally, we will also explore whether latent class trajectories of depressive symptoms can go beyond the dichotomy of remission/non-remission to identify subsets of elders with LLD at highest risk of cognitive decline, neural circuit change, and progression to dementia. This work will set the stage for neural circuit- targeted preventive care to delay dementia in subsets of older patients with LLD. If successful, our work can accelerate therapeutic efforts and innovation targeting the depression- dementia pathway and reduce suffering for large numbers of elders and their families.