Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline.

We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI). We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models. Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = -0.168/-0.175, indirect effect = -0.081/-0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = -0.037, -0.056, and 0.047, respectively). Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.