Abstract
A history of depression is a risk factor for dementia. Despite strong epidemiologic evidence, the pathways linking depression and dementia remain unclear. We assessed structural brain alterations in white and gray matter of frontal-executive and corticolimbic circuitries in five groups of older adults putatively at-risk for developing dementia- remitted depression (MDD), non-amnestic MCI (naMCI), MDD+naMCI, amnestic MCI (aMCI), and MDD+aMCI. We also examined two other groups: non-psychiatric (“healthy”) controls (HC) and individuals with Alzheimer’s dementia (AD). Magnetic resonance imaging (MRI) data were acquired on the same 3T scanner. Following quality control in these seven groups, from diffusion-weighted imaging (n = 300), we compared white matter fractional anisotropy (FA), mean diffusivity (MD), and from T1-weighted imaging (n = 333), subcortical volumes and cortical thickness in frontal-executive and corticolimbic regions of interest (ROIs). We also used exploratory graph theory analysis to compare topological properties of structural covariance networks and hub regions. We found main effects for diagnostic group in FA, MD, subcortical volume, and cortical thickness. These differences were largely due to greater deficits in the AD group and to a lesser extent aMCI compared with other groups. Graph theory analysis revealed differences in several global measures among several groups. Older individuals with remitted MDD and naMCI did not have the same white or gray matter changes in the frontal-executive and corticolimbic circuitries as those with aMCI or AD, suggesting distinct neural mechanisms in these disorders. Structural covariance global metrics suggested a potential difference in brain reserve among groups.
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Acknowledgements
BGP acknowledges the Peter & Shelagh Godsoe Endowed Chair in Late-Life Mental Health. In addition, we thank other members of PACt-MD Study Group; Lillian Lourenco, Daniel M. Blumberger, Christopher R. Bowie, Damian Gallagher, Angela Golas, Ariel Graff, James L. Kennedy, Shima Ovaysikia, Mark Rapoport, Kevin Thorpe, and Nicolaas P.L.G. Verhoeff.
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Rashidi-Ranjbar, N., Rajji, T.K., Kumar, S. et al. Frontal-executive and corticolimbic structural brain circuitry in older people with remitted depression, mild cognitive impairment, Alzheimer’s dementia, and normal cognition. Neuropsychopharmacol. 45, 1567–1578 (2020). https://doi.org/10.1038/s41386-020-0715-y
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