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

• Published in: The American journal of geriatric psychiatry Vol. 31; no. 3; pp. S59 - S60
• Main Authors: Marawi, Tulip, Ainsworth, Nicholas J., Zhukovsky, Peter, Rashidi-Ranjbar, Neda, Rajji, Tarek, Tartaglia, Maria Carmela, Voineskos, Aristotle, Mulsant, Benoit H.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-03-2023
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1016/j.jagp.2022.12.219

Most patients with late-life depression (LLD) have some cognitive impairment, and at least one-third of them 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. To address this knowledge gap, we conducted a systematic review of studies of brain-cognition relationships in LLD or LLD+MCI. We aimed to identify circuits underlying impaired cognition in LLD or LLD+MCI and reveal risk mechanisms for AD.
We searched MEDLINE, PsycINFO, EMBASE, and Web of Science databases from inception through December 11, 2021. We included studies that assessed cognition in patients with LLD or LLD+MCI and acquired: (1) T1-weighted imaging (T1) measuring gray matter (GM) volumes or thickness; or (2) diffusion-weighted imaging (DWI) assessing white matter (WM) integrity.
Our search identified 3,733 eligible studies. After title and abstract screening, 3,507 were excluded and 226 progressed to full-text screening with 175 studies excluded at this stage, yielding 51 studies: 34 studies using T1, 16 using DWI, and 1 using both T1 and DWI. Also, only one T1 and one DWI study compared LLD to MCI or LLD+MCI. Despite some limitations, three main findings emerged from the review. First, overall, the reviewed studies support the role of altered corticolimbic circuitry (particularly in the hippocampus, precuneus, entorhinal cortex, and cingulate cortex) in deficits of learning and memory. DWI studies implicate the cingulate bundle, especially posterior cingulate clusters including the corpus callosum sub-regions, in executive dysfunction. Second, reduced WM integrity was more correlated with executive dysfunction and slowed processing speed than with learning/memory impairments. Third, more consistent brain-cognition relationships emerged for late-onset depression than early-onset depression.
While a reasonable number of studies have explored the relationship between GM or WM and cognitive impairment in LLD, most published studies are limited by their small sample sizes, univariate statistical models, and heterogenous results. Future studies should analyze larger samples of participants with various degrees of cognitive impairment (including those with LLD+MCI) and go beyond univariate statistical models to assess reliable brain-cognition associations.
This project has been supported by the Queen Elizabeth II/Gregory M. Brown Graduate Scholarships in Science and Technology and the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto.