Depression, hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls

Abstract

Objective: The aim of this study was to develop and test a model of depression, hippocampal changes, and cognitive decline.

Method: Participants were 248 community-dwelling, depressed patients and 147 healthy, non-depressed individuals 60 years and older. Participants received a structured interview assessing current depressive symptoms and past depressive episodes, completed cognitive testing with the Mini Mental State Examination (MMSE), and underwent structural Magnetic Resonance Imaging (MRI) of the brain. For up to 10 years, assessment of depressive symptoms and MMSE administration was repeated at least annually, and MRI was repeated every two years.

Results: Regression analyses demonstrated that depression diagnosis at baseline predicted decrease in right (but not left) hippocampal volume over a four-year period. Analyses using structural equation modeling demonstrated that a decrease in left and right hippocampal volumes predicted decrease in MMSE score over four years.

Conclusion: Results provide some evidence for relationships between depression and decrease in right hippocampal volume, and between hippocampal volume and MMSE score. This would be consistent with depression as a causal factor in subsequent cognitive decline. Plausible biological mechanisms include a glucocorticoid cascade or a facilitating effect of depression on amyloid-beta plaque formation. Future studies should examine the relationship between hippocampal volume and specialized memory measures, as well as between depression diagnosis and volume of other brain structures.

Keywords:

• major depressive disorder
• glucocorticoid cascade hypothesis
• neuroimaging
• structural equation modeling

Acknowledgments

This research was supported by NIMH Grant Nos. K01 MH066380, K24 MH70027, R01 MH54846, and P50 MH 60451.