Primate Models of Neurocognitive Aging

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

Magnetic resonance imaging is non-invasive and provides a means of evaluating age-related changes in primate brain structure and functional connectivity associated with individual differences in the cognitive outcome of aging. In a recently published voxel-based morphometry (VBM) analysis, we conducted an unbiased, brain-wide survey to identify the distribution of regional volumes in young and aged animals that significantly correlate with performance on a test of object recognition memory, i.e., a capacity that requires medial temporal lobe integrity and is vulnerable to age-related decline. The overall result was that the anatomical distribution of VBM correlations with memory performance was age-dependent and largely distinct between groups. For young adults, volumetric correlates of task acquisition and recognition accuracy across increasing retention intervals prominently involved precisely the medial temporal lobe regions known to be critical for memory, i.e., the hippocampus and laterally adjacent rhinal cortical areas. Less expected, the cerebellum also emerged as a significant correlate of task performance. Memory in aged subjects, by comparison, failed to correlate with medial temporal volumes and was instead coupled with prefrontal cortex and striatal structure. Statistical interactions were also significant for the medial temporal lobe, prefrontal cortex and cerebellum, confirming that volumetric correlations with cognitive scores in these areas were age-dependent. It is now understood that the adult brain retains a far greater capacity for structural and functional plasticity than previously presumed. Our results suggest that the regional distribution of gray matter volumes coupled with memory is reorganized over the lifespan, consistent with the perspective that the capacity for structural reorganization in the primate brain extends into old age. Prompted by our findings, we have confirmed the translational validity of the observations using data from the Baltimore Longitudinal Study of Aging, in collaboration with investigators in the Brain Aging and Behavior Section of the NIA-IRP. An important future direction is to explore the possibility that the cerebellum mediates the prominent link between decline in physical function and cognitive aging reported in clinical research.