Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure

Background and objective: Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with white matter (WM) disruptions of the fronto-limbic and interhemispheric tracts implicated in mood regulation and episodic memory functions. This work investigates the extent of these WM abnormalities in patients LLD and aMCI when these diseases occur alone and when they coexist Materials and methods: Eighty-four subjects separated into cognitively normal (n = 33), LLD (n = 20), aMCI (n = 18), and comorbid aMCI and LID (n = 13) completed Diffusion Tensor Imaging (DTI) scans. Tract-based spatial statistics was employed to skeletonize multiple DTI indices of the cingulum, corpus callosum, fornix and uncinate fasciculus. Analysis of covariance and post-hoc tests compared group differences. Multiple linear regressions were performed between DTI and behavioral measures for the whole sample and within individual patient groups. Results: Divergent microstructural disruptions were identified in LLD- and aMCI-only groups, whereas the comorbid group showed widespread abnormalities especially in the hippocampal cingulum and fornix tracts. The LID groups also showed significant disruptions in the uncinate fasciculus and corpus callosal tracts. Higher depressive symptom and lower episodic memory scores were associated with increased diffusivity measures in the fornix and hippocampal cingulum across all subjects. Conclusions: Widespread WM microstructural disruptions are present when LLD and aMCI are comorbid - especially in the medial temporal lobe tracts. These WM disruptions may be a marker of disease severity. Also, multiple DTI parameters should be used when evaluating the WM fiber integrity in LLD and aMCI. (C) 2013 Elsevier B.V. All rights reserved.