Regional gray matter loss in late-life onset depression is associated with vascular risks, but not with cerebral amyloidosis


      Although some structural brain changes have been reported in late life onset depression (LLOD), only limited information is available for the causes that underlie to such brain changes in LLOD patients. We first tried to identify LLOD-related regional gray matter (GM) changes, and then investigated the influence of vascular risk factors (VRF) and cerebral amyloidosis on the regional brain changes.


      Non-demented subjects who first experienced major depressive episode after age of 60 years were recruited as LLOD group (N = 29). As normal control (NC) group, non-demented elderly individuals who had no experience of major depressive episode were also included (N = 27). All participants received comprehensive clinical assessment including vascular risk factor (VRF) evaluation, 11C-labeled Pittsburgh Compound B (PiB) positron emission tomography (PET) and magnetic resonance imaging (MRI). Comparison of regional GM volume between LLOD and NC group was performed by using voxel-based morphometry (VBM) at corrected p < 0.05 after family-wise error correction. The regions where LLOD group showed greater volume loss compared to NC group was set as region-of-interest (ROI) for further analyses on the association of VRF and cerebral amyloid deposition .


      There were no significant differences in age, gender and educational level between LLOD and NC groups. Compared to NC, LLOD subjects showed significant regional GM volume loss mainly in the bilateral prefrontal regions including the right medial frontal, left anterior cingulate and left orbitofrontal regions. In linear regression analysis that had the mean GM volume of the ROI as a dependent variable, the presence of VRF showed significant association with the ROI volume in LLOD group after controlling PiB positivity status. In contrast, PiB positivity status did not demonstrate significant association with the mean ROI volume in the same regression model.


      Our findings suggest that vascular risks are major contributors to LLOD and related regional brain changes supporting the ‘vascular depression hypothesis’, while cerebral amyloidosis itself is not likely to be a main player in LLOD.