Abstract
A number of studies have demonstrated that depression or depressive symptoms are a risk factor for subsequently developing cognitive decline or dementia, yet there is some controversy as to the cause(s) of this relationship. Dementia may cause depression; alternatively, depression may be an etiological factor in the development of dementia. In the former case, depressive symptoms may be an early prodrome of dementia, or may be an initial response to the individual’s experience of changes in cognitive functioning. In the latter case, the depressive disorder may accelerate the clinical manifestation of dementing diseases. Specifically, depression may damage the hippocampus through a glucocorticoid cascade, which results in neuronal death in the hippocampus, and consequent hippocampal atrophy. The aim of this dissertation project was to examine the glucocorticoid cascade hypothesis. We studied a sample of depressed, community-dwelling older adults who presented for treatment at a university medical center and an age-matched group of healthy, nondepressed elders. All participants received a structured interview assessing current depressive symptoms and past depressive episodes, cognitive testing with the MMSE, and underwent structural MRI of the brain. Assessment of depressive symptoms and MMSE administration was repeated at least annually, and MRI of the brain was repeated every two years; participants were followed for up to ten years. Regression analyses demonstrated that depression diagnosis at baseline predicted decrease in right (but not left) hippocampal volume over a four-year follow-up period. Analyses using structural equation modeling demonstrated that decrease in left and right hippocampal volume predicted decrease in MMSE score over the four-year follow-up period. Additionally, a structural equation model including only the depressed participants had poor overall fit to the data, but did demonstrate significant paths between baseline depression severity and baseline left hippocampal volume, and between baseline left hippocampal volume and baseline MMSE score. However, in our analyses, depression symptoms and diagnosis did not predict decrease in MMSE score over the four-year follow-up period. Overall, results provide some support for the glucocorticoid hypothesis, in particular the relationship between hippocampal volume and MMSE score. Future studies might examine the relationship between hippocampal volume and specialized memory measures, as well as between depression diagnosis and volume of other brain structures.
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