Neurocognitive Aging in the Monkey

National Institute On Aging

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Abstract

A relatively recent initiative under this project has taken advantage of in vivo brain imaging to evaluate age-related changes in regional volume and functional connectivity specifically in relation to individual differences in the cognitive outcome of aging. In a recent analysis of this sort, volumetric T1-weighted MRI scans were acquired from young (mean = 10.2 years, n = 6) and aged (25.5 years, n = 10) rhesus monkeys on a Siemens Trio 3T scanner, and analyzed by voxel-based morphometry. A key finding was that the regional pattern of brain volumes that correlated with performance on a test of visual recognition memory was distinctly different in young and aged animals. Faster task acquisition inversely correlated with larger medial temporal lobe volume (hippocampus, amygdala, entorhinal cortex, perirhinal cortex, inferotemporal area) in the young, whereas larger prefrontal regions (orbital, ventrolateral, and dorsolateral prefrontal areas) correlated with fewer trials to reach criterion in aged monkeys. When the memory demands of the procedure were increased by imposing longer retention intervals, average recognition accuracy in young monkeys positively correlated with medial temporal lobe, cingulate area, and cerebellum volumes (lobule IV, lobule V, crus I and crus II). In contrast, average performance across delays in the aged brain positively correlated with prefrontal, striatum, and insula volumes. An additional analysis, directly testing for volumetric correlations with memory that interacted with age, broadly confirmed the differences noted when the age groups were considered separately. Interestingly, the results also introduce the cerebellum as potentially important in the context of aging effects on the type of memory traditionally considered a proxy for medial temporal lobe integrity. Additional results suggest that many of the same regions are sensitive to aging as revealed by other neuroimaging modalities, including resting state functional connectivity and cerebral blood flow (examined with arterial spin labeling). Together these findings point to a substantial late life capacity for network reorganization in the primate brain, potentially supporting compensation or adaptive processes that influence the cognitive outcome of aging.