Primate Models of Neurocognitive Aging

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

A relatively new project direction takes advantage of non-invasive, in vivo imaging to evaluate age-related changes in primate brain structure and functional connectivity associated with individual differences in the cognitive outcome of aging. In a recently completed voxel-based morphometry (VBM) analysis, we conducted a conceptually novel, unbiased survey, identifying the brain-wide distribution of regional volumes in young and aged animals that significantly correlate with scores for object recognition memory. The overall result was that the anatomical distribution of VBM correlations with behavior was age-dependent and largely distinct between groups. In young adults, volume correlations with scores for both task acquisition and recognition accuracy across increasing retention delays were prominent precisely in those medial temporal lobe regions known to be critical for task performance, i.e., the hippocampus and laterally adjacent rhinal cortical areas. More surprisingly, the cerebellum also emerged as significant. Task performance in aged subjects, by comparison, failed to correlate with medial temporal structure and were instead coupled with prefrontal cortex volumes. Statistical interactions were also significant in the medial temporal lobe, prefrontal cortex and cerebellum, directly confirming that volumetric correlations with behavior in these areas were age-dependent. Together, the results demonstrate that the regional distribution of gray matter volumes coupled with recognition memory performance changes across the lifespan, consistent with the perspective that the aged primate brain retains a substantial capacity for structural reorganization in association with variability in the cognitive outcome of aging. Prompted by our animal model results, we have also begun probing the potential translational validity of the findings, using data from the Baltimore Longitudinal Study of Aging, in collaboration with investigators in the Brain Aging and Behavior Section of the NIA-IRP. Initial results are encouraging and support the value of preclinical animal research for informing related human studies. A significant focus going forward will be to test the possibility that the cerebellum mediates the prominent link between motor function and cognitive aging observed in clinical research.