Cognitive and Neuroimaging Predictors of Disability in Late Life Depression

描述(申请人提供)：这项K08职业发展奖项目提案的主要目标是描绘认知缺陷和大脑异常对晚年抑郁症患者残疾的相对贡献。这项研究将促进制定干预措施，以最大限度地减少LLD的残疾负担，并将为神经退行性疾病中的残疾研究提供信息。抑郁症是全世界导致残疾的第四大原因，老年抑郁症患者尤其有可能成为残疾人。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都增加了残疾的风险。然而，到目前为止，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。这项研究的重点是确定抑郁症严重程度、ED以及脑结构和白质完整性的变化对LLD患者残疾的独立影响。上述研究目标将通过招募60名65岁以上有LLD、ED和心血管疾病危险因素的人来实现。参与者将参加为期一年的研究，以确定与基线和后续行动中的残疾相关的因素。预测变量将是抑郁症的严重程度，ED的测量，以及在4特斯拉获得的脑磁共振成像(MRI)测量。MRI措施将包括用于评估结构性脑异常的常规结构MRI措施，以及用于评估白质完整性的扩散张量成像(DTI)措施。结果变量将是对身体、情感和认知因素敏感的功能残疾的衡量标准。残疾将通过病人自我报告和举报人的报告进行评估。将获得医疗合并症、身体损害、社会支持和药物使用的衡量标准，以进一步阐明主要预测变量对残疾状况的影响。在为期一年的跟踪评估中，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。来自患有孤立性ED的非抑郁症老年人(n=46)和认知正常的非抑郁症老年人(n=40)的数据将用于在基线和一年的后续评估中与LLD患者在残疾严重程度、认知功能、核磁共振测量和抑郁严重程度方面进行比较。这项研究设计将提供机会来检验我们的假设，即抑郁症严重程度、勃起功能障碍和结构性脑异常各自代表着LLD残疾的独立途径。公共卫生相关性：此外，我们预计脑白质完整性(DTI)的测量将比传统的神经成像标记物更能预测残疾。重要的是，这项研究计划是伴随着免费的职业发展和培训计划，以促进申请人的职业发展作为独立的学术研究人员。

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.