Volumetric Correlates of Spatiotemporal Working and Recognition Memory Impairment in Aged Rhesus Monkeys

Abstract

Spatiotemporal and recognition memory are affected by aging in humans and macaque monkeys. To investigate whether these deficits are coupled with atrophy of memory-related brain regions, T(1)-weighted magnetic resonance images were acquired and volumes of the cerebrum, ventricles, prefrontal cortex (PFC), calcarine cortex, hippocampus, and striatum were quantified in young and aged rhesus monkeys. Subjects were tested on a spatiotemporal memory procedure (delayed response [DR]) that requires the integrity of the PFC and a medial temporal lobe-dependent recognition memory task (delayed nonmatching to sample [DNMS]). Region of interest analyses revealed that age inversely correlated with striatal, dorsolateral prefrontal cortex (dlPFC), and anterior cingulate cortex volumes. Hippocampal volume predicted acquisition of the DR task. Striatal volume correlated with DNMS acquisition, whereas total prefrontal gray matter, prefrontal white matter, and dlPFC volumes each predicted DNMS accuracy. A regional covariance analysis revealed that age-related volumetric changes could be captured in a distributed network that was coupled with declining performance across delays on the DNMS task. This volumetric analysis adds to growing evidence that cognitive aging in primates arises from region-specific morphometric alterations distributed across multiple memory-related brain systems, including subdivisions of the PFC.