Depression related cerebral pathology and its relationship with cognitive functioning: A systematic review

Depression's relationship with cerebral abnormalities and cognitive decline is temporally dynamic. Despite clear clinical utility, understanding depression's effect on cerebral structures, cognitive impairment and the interaction between these symptoms has had limited consideration.

This review summarised studies examining a clinical depression diagnosis or validated scales measuring depressive symptoms, data concerning amyloid-beta (Aβ) levels, brain structure and function focusing on hippocampal alterations, or white matter hyperintensities (WMH), and at least one validated neuropsychological test. Online database searches of: PsycINFO, EMBASE, MEDLINE, and Scopus were conducted to identify potential articles.

While depression was consistently associated with cross-sectionally cognitive decline across multiple domains, the neuropathological basis of this dysfunction remained unclear. Hippocampal, frontal, and limbic dysfunction as well as cortical thinning, WMH, and Aβ burden all provide inconsistent findings, likely due to depression subtypes. The consistency of these findings additionally decreases when examining this relationship longitudinally, as these results are further confounded by pre-dementia states. The therapeutic interventions examined were more efficacious in the younger compared with the older samples, who were characterised by greater WMH and Aβ burden.

The limited number of longitudinal and interventional studies in addition to the heterogeneity of the samples restricts their generalisability.

Symptomatological differences between early-onset and late-onset depression (EOD and LOD) appear crucial in understanding whether late-life depression is the primary or secondary source of cerebral pathology. Though severe cognitive impairments and clearer neuropathological underpinnings are more characteristic of LOD than EOD, the inconsistency of valid biomarkers remains problematic.