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Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment:
Tulip Marawi1, Peter Zhukovsky2, Neda Rashidi-Ranjbar3
1Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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.
Insights
Major depressive disorder (MDD) and mild cognitive impairment (MCI) share brain-cognition links, particularly in those with both conditions. Remitted MDD alone did not show these associations, suggesting MDD may not cause structural brain changes linked to cognitive decline.
Area of Science:
- Neuroscience
- Cognitive Science
- Gerontology
Background:
- Major Depressive Disorder (MDD) is frequently comorbid with cognitive impairment in older adults.
- One-third of older MDD patients meet criteria for Mild Cognitive Impairment (MCI).
- The underlying mechanisms linking MDD and MCI remain poorly understood.
Purpose of the Study:
- To investigate the multivariate associations between brain structural alterations and cognitive function.
- To examine these associations in older patients with remitted MDD (rMDD), MCI, and comorbid rMDD+MCI, alongside healthy controls.
Main Methods:
- Analysis of magnetic resonance imaging (MRI) data from the PACt-MD study.
- Measurement of cortical thickness, subcortical volumes, and white matter integrity.
- Assessment of brain-cognition associations using partial least squares regressions.
Main Results:
- Brain atrophy in specific regions correlated with memory and language deficits.
- Reduced white matter integrity was linked to executive functioning and processing speed deficits.
- These associations were significant in MCI and rMDD+MCI groups, but not in rMDD or healthy controls.
Conclusions:
- Brain-cognition associations found in MCI are extended to the rMDD+MCI group.
- Similar associations were not supported in the rMDD group.
- Early-onset or treated MDD may not be a significant contributor to structural brain alterations associated with cognitive impairment.
