Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity

Abstract

Background: Almost half of older patients with major depressive disorder (MDD) present with cognitive impairment, and one-third meet diagnostic criteria for mild cognitive impairment (MCI). However, mechanisms linking MDD and MCI remain unclear. We investigated multivariate associations between brain structural alterations and cognition in 3 groups of older patients at risk for dementia, remitted MDD (rMDD), MCI, and rMDD+MCI, as well as cognitively healthy nondepressed control participants.

Methods: We analyzed magnetic resonance imaging data and cognitive domain scores in participants from the PACt-MD (Prevention of Alzheimer's Disease With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) study. Following quality control, we measured cortical thickness and subcortical volumes of selected regions from 283 T1-weighted scans and fractional anisotropy of white matter tracts from 226 diffusion-weighted scans. We assessed brain-cognition associations using partial least squares regressions in the whole sample and in each subgroup.

Results: In the entire sample, atrophy in the medial temporal lobe and subregions of the motor and prefrontal cortex was associated with deficits in verbal and visuospatial memory, language skills, and, to a lesser extent, processing speed (p < .0001; multivariate r = 0.30, 0.34, 0.26, and 0.18, respectively). Widespread reduced white matter integrity was associated with deficits in executive functioning, working memory, and processing speed (p = .008; multivariate r = 0.21, 0.26, 0.35, respectively). Overall, associations remained significant in the MCI and rMDD+MCI groups, but not the rMDD or healthy control groups.

Conclusions: We confirm findings of brain-cognition associations previously reported in MCI and extend them to rMDD+MCI, but similar associations in rMDD are not supported. Early-onset and treated MDD might not contribute to structural alterations associated with cognitive impairment.

Trial registration: ClinicalTrials.gov NCT02386670.

Keywords: Cognition; Depression; Geriatric; Magnetic resonance imaging; Mild cognitive impairment; Neuroimaging.