Research reportThe co-existence of geriatric depression and amnestic mild cognitive impairment detrimentally affect gray matter volumes: Voxel-based morphometry study

While late-life depression (LLD) and amnestic mild cognitive impairment (aMCI), alone and in combination, is associated with an increased risk of incident Alzheimer's disease (AD), the neurobiological mechanisms of this link are unclear. We examined the main and interactive effects of LLD and aMCI on the gray matter (GM) volumes in 72 physically healthy participants aged 60 and older. Participants were separated into normal controls, cognitively normal depressed, non-depressed aMCI, and depressed aMCI groups. Optimized voxel-based morphometry estimated GM volumes. The main and interactive effects of LLD and aMCI, and of depressive symptoms and episodic memory deficits on the GM volumes were analyzed. While decreased GM volumes in the mood regulating circuitry structures were associated with depression, GM atrophy in regions essential for various cognitive performance were related to aMCI. LLD-aMCI interactions were associated with widespread subcortical and cortical GM volume loss of brain structures implicated in AD. The interactions between episodic memory deficits and depressive symptom severity are associated with volume loss in right inferior frontal gyrus/anterior insula and left medial frontal gyrus clusters. Our findings suggest that the co-existence of these clinical phenotypes is a potential marker for higher risk of AD.

► Geriatric depression is related to mood-regulating regional gray matter (GM) loss. ► MCI is related to GM volume loss in brain regions involved in cognitive functions. ► Depression-MCI interactions are related to widespread cortical/subcortical GM loss. ► Depressive symptom-memory interactions detrimentally affect frontal and insula GM. ► Co-existence of late-life depression and MCI may be a potential marker of early AD.