Association of White Matter Integrity With Executive Function and Antidepressant Treatment Outcome in Patients With Late-Life Depression

Abstract

Objective: While patients with late-life depression (LLD) often exhibit microstructural white matter alterations that can be identified with diffusion tensor imaging (DTI), there is a dearth of information concerning the links between DTI findings and specific cognitive performance, as well as between DTI measures and antidepressant treatment outcomes.

Design: Neuroimaging and cognitive tests were conducted at baseline in 71 older adults participating in a larger, 8-week duration antidepressant randomized controlled trial. Correlations between DTI measures of white matter integrity evaluated with tract-based spatial statistics, baseline neurocognitive performance, and prospective antidepressant treatment outcome were evaluated.

Results: Fractional anisotropy (FA), an index of white matter integrity, was significantly positively associated with better cognitive function as measured by the Initiation/Perseveration subscale of the Dementia Rating Scale in the bilateral superior longitudinal fasciculus (SLF), bilateral SLF-temporal, and right corticospinal tract (CST). An exploratory analysis limited to these tracts revealed that increased FA in the right CST, right SLF, and right SLF-temporal tracts was correlated with a greater decrease in depressive symptoms. Increased FA in the right CST predicted a greater chance of remission, while increased FA in the right CST and the right SLF predicted a greater chance of treatment response.

Conclusion: In late-life depression LLD subjects, white matter integrity was positively associated with executive function in white matter tracts which act as key connecting structures underlying the cognitive control network. These tracts may play a role as a positive prognostic factor in antidepressant treatment outcome.

Keywords: Diffusion tensor imaging; dementia rating scale; executive function; late-life depression; treatment outcome; white matter integrity.

Figure 1.. Association between fractional anisotropy (FA) and baseline neurocognitive function

Clusters in which FA was significantly positively associated with executive function as measured by I/P subscale of the DRS in LLD patients (TFCE, FWE-corrected p<0.05). Regions showing clusters are overlaid on the mean FA skeleton (green) and MNI152 T1 images. The results are “thickened” using tbss_fill script in TBSS toolbox and displayed in radiological orientation. Abbreviations: I/P subscale of DRS: Initiation/Perseveration subscale of the Dementia Rating Scale, LLD: late-life depression, TFCE: threshold-free cluster enhancement, FWE: family-wise error, TBSS: tract-based spatial statistics, CST: corticospinal tract, SLF: superior longitudinal fasciculus, SLF-temporal: superior longitudinal fasciculus temporal, Left: left hemisphere, Right: right hemisphere.

Figure 2.. Association between fractional anisotropy (FA) and post-pre treatment HRSD-24

Significant negative associations of FA with post-pre HRSD-24 were detected in the SLF, SLF-temporal, and CST, all within the right hemisphere. FA values are plotted on the x axis, and post-pre HRSD-24 are plotted on the y axis. The scatter shows increased FA was correlated with greater decrease in HRSD-24 score. More negative numbers of post-pre HRSD-24 are considered better. These results are “thickened” using tbss_fill script in TBSS toolbox and displayed in radiological orientation. Abbreviations: HRSD-24: 24-item Hamilton Rating Scale for Depression, SLF: superior longitudinal fasciculus, SLF-temporal: superior longitudinal fasciculus temporal, CST: corticospinal tract, Right: right hemisphere, TBSS: tract-based spatial statistics.