Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease.

Neuroimaging features of small vessel disease (SVD) are highly prevalent in older adulthood and associated with significant variability in clinical symptoms, yet the factors predicting these symptom disparities are poorly understood. We employed a novel metric of SVD, peak width of skeletonized mean diffusivity (PSMD), to elucidate the relationship of late-life depression (LLD) to the cognitive presentation of vascular pathology. A total of 109 older adults without a diagnosis of a neurocognitive disorder were enrolled in the study; 44 with major depressive disorder and 65 age-matched controls. Subjects completed neuropsychological testing and magnetic resonance imaging including FLAIR and diffusion tensor imaging sequences, from which white matter hyperintensity volume and diffusion metrics (fractional anisotropy, mean diffusivity, PSMD) were quantified. In hierarchical models, the relationship between vascular burden and cognitive performance varied as a function of diagnostic status, such that the negative association between PSMD and processing speed was significantly stronger in participants with LLD compared to controls. Greater PSMD also predicted poorer performance on delayed memory and executive function tasks specifically among those with LLD, while there were no associations between PSMD and task performance among controls. PSMD outperformed conventional SVD and diffusion markers in predicting cognitive performance and dysexecutive behaviors in participants with LLD. These data suggest that LLD may confer a vulnerability to the cognitive manifestations of white matter abnormalities in older adulthood. PSMD, a novel biomarker of diffuse microstructural changes in SVD, may be a more sensitive marker of subtle cognitive deficits stemming from vascular pathology in LLD.

Cognitive Control Network Homogeneity and Executive Functions in Late-Life Depression.

BACKGROUND: Late-life depression is characterized by network abnormalities, especially within the cognitive control network. We used alternative functional connectivity approaches, regional homogeneity (ReHo) and network homogeneity, to investigate late-life depression functional homogeneity. We examined the association between cognitive control network homogeneity and executive functions. METHODS: Resting-state functional magnetic resonance imaging data were analyzed for 33 older adults with depression and 43 healthy control subjects. ReHo was performed as the correlation between each voxel and the 27 neighbor voxels. Network homogeneity was calculated as global brain connectivity restricted to 7 networks. T-maps were generated for group comparisons. We measured cognitive performance and executive functions with the Dementia Rating Scale, Trail-Making Test (A and B), Stroop Color Word Test, and Digit Span Test. RESULTS: Older adults with depression showed increased ReHo in the bilateral dorsal anterior cingulate cortex (dACC) and the right middle temporal gyrus, with no significant findings for network homogeneity. Hierarchical linear regression models showed that higher ReHo in the dACC predicted better performance on Trail-Making Test B (p < .001; R2 = .49), Digit Span Backward (p < .05; R2 = .23), and Digit Span Total (p < .05; R2 = .23). Used as a seed, the dACC cluster of higher ReHo showed lower functional connectivity with bilateral precuneus. CONCLUSIONS: Higher ReHo within the dACC and right middle temporal gyrus distinguish older adults with depression from control subjects. The correlations with executive function performance support increased ReHo in the dACC as a meaningful measure of the organization of the cognitive control network and a potential compensatory mechanism. Lower functional connectivity between the dACC and the precuneus in late-life depression suggests that clusters of increased ReHo may be functionally segregated.