Brain-cognition relationships in late-life depression: a systematic review of structural magnetic resonance imaging studies

Background Most patients with late-life depression (LLD) have cognitive impairment, and at least one-third meet diagnostic criteria for mild cognitive impairment (MCI), a prodrome to Alzheimer’s dementia (AD) and other neurodegenerative diseases. However, the mechanisms linking LLD and MCI, and brain alterations underlying impaired cognition in LLD and LLD + MCI remain poorly understood. Methods To address this knowledge gap, we conducted a systematic review of studies of brain-cognition relationships in LLD or LLD + MCI to identify circuits underlying impaired cognition in LLD or LLD + MCI. We searched MEDLINE, PsycINFO, EMBASE, and Web of Science databases from inception through February 13, 2023. We included studies that assessed cognition in patients with LLD or LLD + MCI and acquired: (1) T1-weighted imaging (T1) measuring gray matter volumes or thickness; or (2) diffusion-weighted imaging (DWI) assessing white matter integrity. Due to the heterogeneity in studies, we only conducted a descriptive synthesis. Results Our search identified 51 articles, resulting in 33 T1 studies, 17 DWI studies, and 1 study analyzing both T1 and DWI. Despite limitations, reviewed studies suggest that lower thickness or volume in the frontal and temporal regions and widespread lower white matter integrity are associated with impaired cognition in LLD. Lower white matter integrity in the posterior cingulate region (precuneus and corpus callosum sub-regions) was more associated with impairment executive function and processing speed than with memory. Conclusion Future studies should analyze larger samples of participants with various degrees of cognitive impairment and go beyond univariate statistical models to assess reliable brain-cognition relationships in LLD.