Cognitive and Neuroimaging Predictors of Disability in Late Life Depression

描述（由申请人提供）：这个K08职业发展奖项目提案的总体目标是描述认知缺陷和大脑异常对晚年抑郁症（LLD）个体残疾的相对贡献。这项研究将促进干预措施的发展，以尽量减少LLD的残疾负担，也将为神经退行性疾病的残疾研究提供信息。抑郁症是全球第四大致残原因，老年抑郁症患者尤其有致残的风险。LLD与脑血管疾病（CVD）和执行功能障碍（ED）的认知缺陷密切相关，CVD和ED都会增加残疾的风险。然而，迄今为止，认知和神经生物学因素对LLD残疾的相对贡献仍未得到充分研究。该研究的具体重点是确定抑郁症严重程度、ED、脑结构和白质完整性变化对LLD残疾的独立影响。既定的研究目标将通过招募60名65岁以上患有LLD、ED和心血管疾病危险因素的个体来实现。参与者将参加为期一年的研究，以确定基线和随访时与残疾相关的因素。预测变量将是抑郁严重程度、ED测量和4特斯拉时获得的脑磁共振成像（MRI）测量。MRI测量将包括用于评估脑结构异常的常规结构MRI测量和用于评估白质完整性的弥散张量成像（DTI）测量。结果变量将是对身体、情感和认知因素敏感的功能残疾的测量。残疾将通过患者自我报告和举报人的报告进行评估。将获得医疗合并症、身体损伤、社会支持和药物使用的测量，以进一步阐明主要预测变量对残疾状况的影响。在为期一年的随访评估中，将获得残疾状况、抑郁严重程度和认知功能的纵向测量，以评估与残疾不良病程相关的因素。来自孤立性ED的非抑郁老年人（n=46）和认知正常的非抑郁老年人（n=40）的数据将用于与LLD患者在基线和一年随访评估时的残疾严重程度、认知功能、MRI测量和抑郁严重程度进行比较。这项研究设计将提供机会来检验我们的假设，即抑郁严重程度、ED和结构性脑异常各自代表LLD中导致残疾的独立途径。公共卫生相关性：此外，我们预计白质完整性（DTI）的测量将比传统的神经成像标记更能预测残疾。重要的是，该研究计划附有免费的职业发展和培训计划，以促进申请人作为独立学术研究人员的职业发展。

DESCRIPTION (provided by applicant): The overarching goal of this K08 Career Development Award project proposal is to delineate the relative contributions of cognitive deficits and brain abnormalities on disability for individuals with late life depression (LLD). This research will facilitate the development of interventions to minimize the burden of disability in LLD and will also inform studies of disability in neurodegenerative diseases. Depression is the fourth leading cause of disability worldwide and elderly depressed individuals are particularly at risk to become disabled. LLD has been strongly linked to cerebrovascular disease (CVD) and cognitive deficits of executive dysfunction (ED) and both CVD and ED confer additional risk for disability. However, to date, the relative contributions of cognitive and neurobiological factors on disability in LLD remain under-investigated. The specific focus of the proposed study is to determine the independent effects of depression severity, ED, and changes in brain structure and white matter integrity on disability in LLD. The stated research goal will be achieved by recruiting 60 individuals over the age of 65 with LLD,ED, and risk factors for CVD. Participants will be enrolled in the study for one year to determine factors associated with disability at baseline and at follow-up. The predictor variables will be depression severity, measures of ED, and brain Magnetic Resonance Imaging (MRI) measures obtained at 4 Tesla. MRI measures will include conventional structural MRI measures to evaluate structural brain abnormalities and diffusion tensor imaging (DTI) measures utilized to assess white matter integrity. Outcome variables will be measures of functional disability that are sensitive to physical, emotional, and cognitive factors. Disability will be assessed by patient self-report and by report of an informant. Measures of medical comorbidity, physical impairment, social support and medication use will be obtained to further clarify the impact of the primary predictor variables on disability status. Longitudinal measures of disability status, depression severity, and cognitive functioning will be obtained at a one-year follow-up assessment to evaluate factors associated with poor course of disability. Data from non-depressed older adults with isolated ED (n=46) and cognitively normal, non-depressed older adults (n=40) will be available for comparison to LLD individuals for disability severity, cognitive functioning, MRI measures, and depression severity at baseline and one-year follow up evaluations. This research design will offer the opportunity to test our hypothesis that depression severity, ED, and structural brain abnormalities each represent independent pathways to disability in LLD. PUBLIC HEALTH RELEVANCE: Further, we expect that measures of white matter integrity (DTI) will be stronger predictors of disability than traditional neuroimaging markers. Importantly, this research proposal is accompanied by complimentary career development and training plan to facilitate the development of the applicant's career as an independent academic researcher.