P1‐358: White matter integrity in first‐episode late‐onset depression using tract‐based spatial statistics (2011)

The relationship between depression and cognitive impairment is very complex. Previous studies have demonstrated that late-onset depression (LOD) is associated with multi-domain cognitive impairment, including memory, executive function and attention. However, the mechanism of cognitive impairment in LOD remains unclear. In mild cognitive impairment, abnormalities of white matter (WM) measured with diffusion tensor imaging (DTI) technique have been reported. This study was designed to, using tract-based-spatial-statistics (TBSS), explore the whole-brain differences in white matter integrity in first-episode LOD. A total of 58 subjects were scanned with a Siemens 3T MRI scanner. The diffusion tensor images were acquired with a spin-echo single-shot EPI sequence with 64 encoding directions. The demographic characteristics were matched between the two groups. The NC subjects (n = 30; 17 male, 13 female) had a mean age ± stdev of 72.1±7.5, and the LOD subjects (n = 28; 13 male, 15 female) had a mean age ± stdev of 70.4±7.0. All preprocessing and statistical analysis were performed with the FSL software package from Oxford's Analysis Group (http://fsl.fmrib.ox.ac.uk/fsl). The FA maps from 58 brains were analyzed with TBSS, with registration of individual FA maps to the most representative FA map within the cohort. MD maps were processed using the same nonlinear registration and projection vectors as the FA maps. Once the skeletonized maps were obtained, the FA and MD values were compared in a voxel-wise fashion between the NC and LOD group using a permutation test with threshold-free cluster enhancement. All tests were taken to be significant at p < 0.05. Group-wise voxel-based comparisons between the NC and LOD revealed significantly decreased FA values in LOD subjects corresponding to the neural tracts of the corpus callosum and the forceps minor of the cingulate gyrus. Significant decreases in FA were also found in the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus of the sagittal stratum and anterior corona radiata. No significant differences were noted for comparison of MD maps. The comparison of FA and MD maps between the NC and LOD groups revealed significant differences in FA maps corresponding to white matter tracts associated with the limbic, parietal, frontal, and temporal lobes. The inferior fronto-occipital fasciculus, which integrates auditory and visual association cortices with the prefrontal cortex, the inferior longitudinal fasciculus, which is involved in the integration of auditory and speech nuclei, and the uncinate fasciculus, which plays a role in memory integration, are all associated with cognitive emotional function. Decreased FA values in these tracts indicate a possible change in neuron cell integrity or fiber degeneration relative to NC subjects, while no significant changes in MD values suggest conservation of cell-matrix integrity between the two groups. These findings are in agreement with the increasing body of evidence from literature, which hypothesizes that LOD may be associated with acute microstructural WM changes. However, the relationship between microstructural WM changes and the cognitive impairment warrants further investigations.