Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

Late-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology.

We studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance.

LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ²₁ = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ²₁ > 20.14, p < .001), greater anhedonia (Wald χ²₁ = 7.02, p = .008) and fatigue (Wald χ²₁ = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ²₁ > 4.65, p < .031), executive function (Wald χ²₁ = 7.18, p = .007), and working memory (Wald χ²₁ > 4.29, p < .038).

LLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.