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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Evans, Jovier D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Connecticut
Schools of Medicine
United States
Zip Code
Deng, Yi; McQuoid, Douglas R; Potter, Guy G et al. (2018) Predictors of recurrence in remitted late-life depression. Depress Anxiety 35:658-667
Rajkowska, Grazyna; Mahajan, Gouri; Legutko, Beata et al. (2017) Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression. Neuroscience 359:30-39
Riddle, Meghan; Potter, Guy G; McQuoid, Douglas R et al. (2017) Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression. Am J Geriatr Psychiatry 25:1123-1134
Johnson, Anne D; McQuoid, Douglas R; Steffens, David C et al. (2017) Effects of stressful life events on cerebral white matter hyperintensity progression. Int J Geriatr Psychiatry 32:e10-e17
Manning, Kevin J; Chan, Grace; Steffens, David C (2017) Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression. Am J Geriatr Psychiatry 25:220-229
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
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
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 24:42-49
Saha, Sayoni; Hatch, Daniel J; Hayden, Kathleen M et al. (2016) Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes. Am J Geriatr Psychiatry 24:870-8
Potter, Guy G; McQuoid, Douglas R; Whitson, Heather E et al. (2016) Physical frailty in late-life depression is associated with deficits in speed-dependent executive functions. Int J Geriatr Psychiatry 31:466-74

Showing the most recent 10 out of 159 publications