Dorsal Cingulate Activity and Cognitive Decline in Late-Life Depression

晚年抑郁症中的背扣带回活动和认知能力下降

• 批准号: 8680374
• 负责人: David J. Madden
• 金额: $ 39.25万
• 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: 2012-09-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680374
• 关键词: Acute; Affective; Algorithms; Alzheimer' s Disease; Anterior; Antidepressive Agents; Attention; Base of the Brain; Biological Markers; Brain; Brain region; Cerebrovascular Disorders; Classification; Clinical; Cognition; Cognitive; Comorbidity; Dementia; Depressed mood; Detection; Disease remission; Dorsal; Early Intervention; Early identification; Emotional; Frequencies; Functional disorder; Future; Goals; High Prevalence; Hippocampus (Brain); Image; Impaired cognition; Individual; Institutes; Intervention; Investigation; Language; Link; Longitudinal Studies; Measures; Medical; Memory; Mental Depression; Monitor; Neuronal Plasticity; Neuropsychological Tests; Outcome; Outcome Study; Participant; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Population; Prefrontal Cortex; Prevention program; Public Health; Quality of life; Recruitment Activity; Research; Rest; Risk; Sampling; Scanning; Secondary to; Severities; Signal Transduction; System; Testing; Time; Vascular Dementia; Visuospatial; alternative treatment; attenuation; base; blood oxygen level dependent; cognitive control; cognitive function; data modeling; depressive symptoms; executive function; experience; follow-up; geriatric depression; high risk; improved; innovation; meetings; mild cognitive impairment; mortality; neuroimaging; neuromechanism; outcome forecast; relating to nervous system; response; skills; therapy development

DESCRIPTION (provided by applicant): Cognitive impairment frequently occurs in late-life depression (LLD), which increases the risk of dementia, mortality, and medical comorbidity. While cognitive impairment secondary to depression may resolve after successful treatment, persistent cognitive impairment or cognitive decline may occur in some patients even after remission from depressive symptoms. Individuals with cognitive decline over years have an increased risk of developing either Alzheimer's disease or vascular dementia. Identifying individuals who are at risk for developing cognitive decline is vital for early intervention strategies. Therefore, the long-term goals of the proposed project are to better understand the neural mechanisms linking depression and cognitive impairment, to establish biomarkers for early identification of depressed individuals at risk for cognitive impairment, and to understand the neural plasticity of LLD with and without cognitive impairment following prevention programs and clinical interventions. Our preliminary study indicates that reduced dorsal anterior cingulate (dACC) activation during target detection is associated with future cognitive decline in LLD. Reduced dACC- hippocampus connectivity is also found in LLD patients with cognitive impairment. Given that the dACC is one of the regions that is involved in both AD and depression, and because deficits in this region can result in broad abnormalities in functional connectivity across affective and cognitive networks in depression, we hypothesize that aberrant dACC activity (i.e., reduced dACC activation and reduced hippocampus-dACC connectivity) will predict cognitive decline in LLD. To test this hypothesis, we propose a two-year longitudinal neuroimaging study in 140 medication-free LLD patients. The objectives of this proposal are to investigate the neural mechanisms in LLD associated with cognitive decline and to examine whether our proposed imaging marker can predict which individuals are at a high risk of cognitive decline. All participants will be scanned during a resting state and during a simple target detection task at baseline, and at year 2. Our specific aims are: 1) to characterize the cognitive profile associated with reduced dACC activity in patients with acute LLD; 2) to examine whether reduced dACC activity at baseline predicts two-year cognitive decline; and 3) to examine the association between two-year changes in cognition with two-year changes in brain activation and functional connectivity in LLD patients. We hypothesize that LLD patients with reduced dACC activity will have lower cognitive function at baseline and greater cognitive decline over the two-year follow-up period. The proposed research is innovative because we plan to characterize a clinical profile in LLD based on functional activation pattern. The approach will stimulate future "brain-based classification" studies to predict individuals' clinica status based upon brain activation. The proposed research is significant because positive outcomes of the study will potentially assist clinical identification of LLD individuals who are at risk of cognitive decline. The dACC dysfunction pattern may also serve as a neural marker to monitor clinical intervention.

描述（由申请人提供）：认知障碍经常发生在晚期抑郁症（LLD）中，这增加了痴呆，死亡率和医疗合并症的风险。尽管成功治疗后，继发性抑郁症的认知障碍可能会解决，但即使从抑郁症状缓解后，某些患者也可能会发生持续的认知障碍或认知能力下降。多年来认知能力下降的人患阿尔茨海默氏病或​​血管性痴呆症的风险增加。识别有面临认知能力下降风险的人对于早期干预策略至关重要。因此，拟议项目的长期目标是更好地理解与抑郁症和认知障碍联系起来的神经机制，以建立生物标志物，以尽早鉴定有认知障碍风险的抑郁症患者，并在预防计划和临床干预措施后与LLD和没有认知障碍的LLD的神经可塑性。我们的初步研究表明，在目标检测过程中，背扣带（DACC）激活减少与LLD的未来认知下降有关。在认知障碍的LLD患者中，DACC-海马连通性也降低。鉴于DACC是涉及AD和抑郁症的区域之一，并且由于该地区的缺陷会导致抑郁症的情感和认知网络跨抑郁症的功能连通性的广泛异常，因此我们假设DACC活性异常（即，DACC激活以及降低了HippocAcpus-DACC连接性的降低）会预测CopnITIVE copnitive copnive copnitive copnitive in copnitive in l dld。为了检验这一假设，我们提出了一项为期两年的纵向神经影像学研究，对140名无药物LLD患者。该提案的目标是研究与认知下降相关的LLD的神经机制，并检查我们提出的成像标记是否可以预测哪些人有认知能力下降的高风险。所有参与者将在静止状态和基线的简单目标检测任务中进行扫描，在第2年。我们的具体目的是：1）表征与急性LLD患者DACC活性降低相关的认知概况； 2）检查基线下DACC活性的降低是否预测了两年的认知能力下降； 3）检查了两年的认知变化与LLD患者的两年变化与大脑激活和功能连通性的变化之间的关联。我们假设在基线时，DACC活性降低的LLD患者的认知功能将降低，并且在两年的随访期内认知能力下降较高。拟议的研究具有创新性，因为我们计划基于功能激活模式来表征LLD中的临床特征。该方法将刺激未来的“基于大脑的分类”研究，以根据大脑激活来预测个体的临床状况。拟议的研究很重要，因为该研究的积极结果将有可能有助于临床鉴定在 认知能力下降的风险。 DACC功能障碍模式也可以作为监测临床干预的神经标记。