This is a renewal of a project that has enrolled 707 subjects, including 527 depressed elderly patients and 180 non-depressed elderly controls over the past ten years. Over the next five years we will follow 254 active subjects, including 182 patients and 72 controls, with a focus on genetic and post-mortem neuroanatomical correlates of mood and cognition. These subjects are currently being followed in the current study, and no new subjects will be added. Analyses will be performed on all 757 subjects who have been enrolled. Detailed psychosocial, functional, clinical, psychiatric, medical, neurological, and cognitive assessments will continue to be obtained at defined points during follow-up. At least two brain MRI studies will have been performed on the majority of subjects at a two year interval;the existing MRI data will be used in longitudinal analyses as well. The principal outcome measures are trajectory of mood and cognition and on post-mortem neuroanatomical and neuropathological brain changes. The analysis plan focuses on examination of risk for recurrence and chronicity of depression and risk for cognitive decline and later dementia using the following independent variables: baseline cognitive profile, baseline fractional anisotropy (FA) and change in FA, functional MRI measure of resting state connectivity, and depression course. The project will preserve past methodological advances by combining psychiatric assessments with psychosocial and psychobiological perspectives. In a study design that employs carefully defined treatment algorithms, we will test specific hypothesis regarding mood outcomes and cognitive decline and dementia. A novel feature of the study is examination of post-mortem brain changes, specifically alterations in basolateral amygdala. It is expected that the results from this study will clarify the relationship between depression and dementia in the elderly. It will also add to the literature on neuroimaging factors and the long-term outcome of depression in a clinical setting. It is the first prospective longitudinal study in depression to correlate clinical in vivo data on well characterized patients with subsequent post-mortem morphometric analyses.

Public Health Relevance

Depression is a risk factor for cognitive decline and dementia in older adults, but the biological underpinnings for this observation are not clear. This study seeks to further our scientific understanding of the relationship between depression and cognitive impairment. If successful, we will be able to identify which older depressed adults are at risk for dementia and will be in a position to intervene to prevent cognitive decline in this targeted population.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH054846-18
Application #
8613505
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Evans, Jovier D
Project Start
1995-07-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
18
Fiscal Year
2014
Total Cost
$452,296
Indirect Cost
$21,571
Name
University of Connecticut
Department
Psychiatry
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Hybels, Celia F; Pieper, Carl F; Blazer, Dan G et al. (2016) Heterogeneity in the three-year course of major depression among older adults. Int J Geriatr Psychiatry 31:775-82
Rubinow, Marisa J; Mahajan, Gouri; May, Warren et al. (2016) Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study. Brain Struct Funct 221:171-84
Manning, Kevin J; Chan, Grace; Steffens, David C (2016) Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression. Am J Geriatr Psychiatry :
Hybels, Celia F; Pieper, Carl F; Payne, Martha E et al. (2016) Late-life Depression Modifies the Association Between Cerebral White Matter Hyperintensities and Functional Decline Among Older Adults. Am J Geriatr Psychiatry 24:42-9
Dzierzewski, Joseph M; Potter, Guy G; Jones, Richard N et al. (2015) Cognitive functioning throughout the treatment history of clinical late-life depression. Int J Geriatr Psychiatry 30:1076-84
Fieo, Robert; Mukherjee, Shubhabrata; Dmitrieva, Natalia O et al. (2015) Differential item functioning due to cognitive status does not impact depressive symptom measures in four heterogeneous samples of older adults. Int J Geriatr Psychiatry 30:911-8
Dmitrieva, Natalia O; Fyffe, Denise; Mukherjee, Shubhabrata et al. (2015) Demographic characteristics do not decrease the utility of depressive symptoms assessments: examining the practical impact of item bias in four heterogeneous samples of older adults. Int J Geriatr Psychiatry 30:88-96
Gross, Alden L; Mungas, Dan M; Crane, Paul K et al. (2015) Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results. Psychol Aging 30:863-80
Riddle, Meghan; McQuoid, Douglas R; Potter, Guy G et al. (2015) Disability but not social support predicts cognitive deterioration in late-life depression. Int Psychogeriatr 27:707-14
Potter, Guy G; McQuoid, Douglas R; Steffens, David C (2015) Appetite loss and neurocognitive deficits in late-life depression. Int J Geriatr Psychiatry 30:647-54

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