Disentangling Late Life Depression, Vascular Lesions and Functional Decline

解决晚年抑郁、血管病变和功能衰退的问题

• 批准号: 8443463
• 负责人: CELIA F HYBELS
• 金额: $ 7.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-24 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443463
• 关键词: Activities of Daily Living; Address; Adult; Affect; Age; Biological Markers; Blood Vessels; Brain; Caring; Clinical; Cognition; Cognitive; Comorbidity; Complex; Cross-Sectional Studies; Data; Data Analyses; Depressed mood; Diagnosis; Elderly; Epidemiologist; Goals; Intervention; Lead; Lesion; Longitudinal Studies; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mediating; Mediator of activation protein; Medical; Mental Depression; Modeling; Nature; Neurocognitive; Outcome; Pathology; Pathway interactions; Patient Self-Report; Patients; Physical Function; Populations at Risk; Prevention; Principal Investigator; Protocols documentation; Public Health; Reporting; Research; Risk; Risk Factors; Sampling; Series; Signal Transduction; Syndrome; Time; Variant; Work; adverse outcome; cerebrovascular; clinically relevant; cognitive change; comparison group; depressive symptoms; disability; experience; functional decline; functional disability; functional outcomes; functional status; geriatric depression; indexing; interest; modifiable risk; multidisciplinary; older patient; older women; parallel processing; prevent; public health relevance; white matter

DESCRIPTION (provided by applicant): Functional impairment has been well established as an adverse consequence of late-life depression. The complex relationship between depression and functional status in older adults includes its bidirectional nature. Mechanistically, these conditions may be causes or consequences of each other, part of the same syndrome or parallel processes from a shared risk factor. Recent research has identified increased white matter hyperintensities (WMH), a biomarker signaling vascular changes in the brain, as a predictor of functional decline outside of depression. These WMH are also commonly seen in late-life depression. Although in cross-sectional studies WMH are associated with functional impairment in depressed older patients, it is not known whether increases in WMH volume predicts functional decline in older adults with major depression. More importantly, it is not known how the presence or absence of depression may impact or contribute to the relationship between WMH volume and functional decline in late life. Concurrent changes in cognition may also affect these relationships among WMH, depression, and functional status. The proposed work offers the unique opportunity to clarify within a sample of 518 older adults initially diagnosed with major depression and a comparison group of 195 initially never depressed older adults followed over time the extent to which white matter hyperintensities predict trajectories of depression and physical and cognitive functional decline. Given the high proportion of older adults with functional limitations and depression identified as a leading cause of disability, information to disentangle the complexity between depression and functional decline through a shared biomarker has much clinical relevance. For example, it may support better management of cerebrovascular risk factors among older depressives in order to prevent functional decline. Using data from the NeuroCognitive Outcomes of Depression in the Elderly (NCODE) study, we propose a secondary data analysis plan to address two potential pathways underlying these complex relationships: 1) depression and physical/cognitive functional decline as parallel processes predicted by increased WMH volume, and 2) depression as a mediator and/or moderator in the relationship between white matter pathology and functional variation and decline among older adults, suggesting a unique contribution of depression. The NCODE, now in its sixteenth year, is a naturalistic treatment study of adults age 60 or older diagnosed with major depression and a comparison group of never depressed older adults followed over time. WMH data were collected at two-year intervals using an approved MRI protocol. The proposed analysis plan includes the use of mixed models to examine the contribution of depression to the cross-sectional and longitudinal associations between WMH and functional status. As well as adjusting for correlated measures over time, mixed models allow changes in other variables such as medical comorbidity to be included in the longitudinal models.

描述(由申请人提供)：功能障碍已经被很好地确定为老年抑郁症的不良后果。老年人抑郁和功能状态之间的复杂关系包括其双向性质。从机制上讲，这些情况可能是彼此的原因或结果，可能是同一综合症的一部分，也可能是共同风险因素的平行过程。最近的研究发现，脑白质高强度(WMH)的增加是抑郁症以外的功能下降的预测指标。WMH是大脑中发出血管变化信号的生物标志物。这些WMH在老年抑郁症中也很常见。尽管在横断面研究中，WMH与老年抑郁症患者的功能损害有关，但尚不清楚WMH容量的增加是否预示着患有重度抑郁症的老年人的功能下降。更重要的是，目前还不知道抑郁症的存在或不存在如何影响或促成晚年WMH量与功能衰退之间的关系。认知的同时变化也可能影响WMH、抑郁和功能状态之间的关系。这项拟议的工作提供了一个独特的机会，在518名最初被诊断为重度抑郁症的老年人样本中，以及195名最初从未抑郁的老年人的对照组中，随着时间的推移，白质高信号在多大程度上预测了 抑郁以及身体和认知功能的下降。鉴于功能受限和抑郁症被认为是导致残疾的主要原因的老年人的高比例，通过共享的生物标记物来解开抑郁症和功能衰退之间的复杂性的信息具有很大的临床意义。例如，它可能支持更好地管理老年抑郁症患者的脑血管危险因素，以防止功能下降。使用老年抑郁症的神经认知结果(NCode)研究的数据，我们提出了一个二级数据分析计划，以解决这些复杂关系背后的两条潜在途径：1)抑郁和身体/认知功能下降是由WMH体积增加预测的平行过程，2)抑郁作为白质病理与老年人功能变异和下降之间关系的中介和/或调节因素，表明抑郁症具有独特的贡献。NCode现已进入第16个年头，它是一项自然主义治疗研究，对象是60岁或以上的被诊断为严重抑郁症的成年人，以及一组从未抑郁的老年人，随着时间的推移进行跟踪调查。使用批准的MRI方案每两年收集一次WMH数据。拟议的分析计划包括使用混合模型来检查抑郁对WMH和功能状态之间的横断面和纵向关联的贡献。除了随时间调整相关指标外，混合模型还允许在纵向模型中包括其他变量的变化，如医疗合并症。