Brain structural correlates of trajectories to cognitive impairment in men with and without HIV disease.

There are distinct trajectories to cognitive impairment among participants in the Multicenter AIDS Cohort Study (MACS). Here we analyzed the relationship between regional brain volumes and the individual trajectories to impairment in a subsample (n = 302) of the cohort. 302 (167 HIV-infected; mean age = 55.7 yrs.; mean education: 16.2 yrs.) of the men enrolled in the MACS MRI study contributed data to this analysis. We used voxel-based morphometry (VBM) to segment the brain images to analyze gray and white matter volume at the voxel-level. A Mixed Membership Trajectory Model had previously identified three distinct profiles, and each study participant had a membership weight for each of these three trajectories. We estimated VBM model parameters for 100 imputations, manually performed the post-hoc contrasts, and pooled the results. We examined the associations between brain volume at the voxel level and the MMTM membership weights for two profiles: one considered "unhealthy" and the other considered "Premature aging." The unhealthy profile was linked to the volume of the posterior cingulate gyrus/precuneus, the inferior frontal cortex, and the insula, whereas the premature aging profile was independently associated with the integrity of a portion of the precuneus. Trajectories to cognitive impairment are the result, in part, of atrophy in cortical regions linked to normal and pathological aging. These data suggest the possibility of predicting cognitive morbidity based on patterns of CNS atrophy.