RESULTS OF THE ADNI-DEPRESSION STUDY: Session 323

Abstract

Results Of The ADNI-Depression Study. Overview: Late life depression (LLD) is one of the most common mental health disorders with which older patients are afflicted. LLD is complicated by the common co-occurrence of cognitive impairment (CI). Estimates suggest as many as 50-60% of older depressed patients may have mild cognitive deficits however the mechanisms contributing to CI are unclear. The ADNI-Depression (ADNI-D) Study is a 5-year two-site (University of California San Francisco and the University of Pittsburgh) NIMH sponsored study of late life depression. The study aims to characterize cognitive functioning patients with LLD and clarify neurobiological mechanisms contributing to cognitive impairment and accelerated cognitive decline in this patient population. The ADNI -D study partners with the Alzheimer's Disease Network Initiative (ADNI) and utilizes its core labs for data management, brain imaging, and biomarker assessments. The ADNI D study has been designed to focus on evaluating the impact of reduced cerebral blood flow, cortical atrophy, white matter disease, and amyloid deposition on cognitive impairment in LLD. The study is longitudinal; after an initial assessment subject are followed for 2 ½ years. ADNI-D is committed to rapid data sharing of the ADNI-D data. This session will present initial data from the ADNI-Depression Study baseline evaluation and will be organized into 4 topic areas. ADNI-D Methodology and Sample Characteristics (Nelson) The ADNI D sample is a well characterized sample of older adults with depression. The ADNI D methodology facilitates comparisons of this cohort of LLD participants with the larger ADNI study of non-depressed older adults with normal cognition, Mild Cognitive Impairment (MCI), and dementia in order to clarify neurobiological mechanisms contributing to cognitive impairment and accelerated cognitive decline. This session will be focused on describing the ADNI-D methodology for participant enrollment and data collection and to report ADNI D sample (n=121) characteristics for depression severity, lifetime history of depression and depression treatment, and functional impairment. Specifically, participant enrollment criteria and methods for the assessment of depression severity and lifetime history of depression and depression treatments will be summarized. Additionally, standardized methodology for collection of neuroimaging data, biomarkers, and data management will be presented. Cognitive Functioning in the ADNI Depression cohort (Morin). The clarification of types and severity of cognitive dysfunction in LLD remains a significant area of research. This session will focus on identifying the cognitive impairment rates of participants with LLD in the ADNI-D study at baseline, highlighting methodological considerations for matching subjects to ADNI participants on basis of cognitive functioning for biomarker analyses, and to assess the relationship of subjective cognitive complaints and ApoE status with objective measures cognitive performance. Association of Cortical Atrophy, White Matter Lesions, and Amyloid Accumulation with Cognition in Late Life Depression (Mackin) Cognitive impairment (CI) in LLD is often characterized by deficits of executive functioning (EF), memory, and language and LLD has been strongly linked to accelerated rates of cognitive decline in older adults. However, the causes of CI in LLD are not clear, in part due to limitations of previous work which have lacked comparisons to well characterized non-depressed older adults with CI caused by neurodegenerative diseases that are often concurrent with LLD, such as the early stages of Alzheimer's disease (AD) and cerebrovascular disease (CVD). The ADNI-D study will facilitate clarification of neurobiological mechanisms contributing to CI in LLD. This session will be focused on evaluating the impact of reduced cerebral blood flow (hypoperfusion), cortical atrophy, and amyloid deposition on CI in LLD in the context of previously documented relationships between CI and subcortical white matter abnormalities and genetic risk factors. Functional Network Level Pathophysiologic Abnormalities Associated with Late Life Depression (Tosun) Cognitive impairment, particularly in the domains of information processing speed, executive functioning, and memory, in LLD is consistent with neurobiological conceptualizations of LLD as being heavily mediated by extended neural networks comprised of the orbitofrontal, medial prefrontal, and cingulate cortices, and anatomical connections with the temporal and parietal lobes, and basal ganglia. By disturbing the normal function and dynamics of different brain networks, the pathophysiological mechanisms of LLD may generate different specific clinical symptoms. Therefore we examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in LLD and whether such biomarkers may act as predictors, moderators, and mediators of depressive symptoms. This might facilitate development of personalized treatments based on a better understanding of the pathophysiological mechanisms of late life depression.