Vulnerability of the Orbitofrontal Cortex to Age‐Associated Structural and Functional Brain Changes

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Abstract
Cross-sectional and longitudinal findings from the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study indicate that the orbitofrontal cortex (OFC) is among those regions vulnerable to age-associated tissue loss in older adults without dementia. Neuropathologic and recent in vivo amyloid imaging studies indicate that the OFC is also among the earliest neocortical regions to show deposition of amyloid plaques in aging and Alzheimer's disease. We performed behavioral and imaging studies to investigate age effects on specific aspects of OFC function. We compared performance in young (age 20-40) and old (age 60 and older) adults on cognitive tasks selected for differential sensitivity to OFC versus dorsolateral prefrontal cortex (DLPFC). Overall, greater age differences were seen in the OFC tasks compared to DLPFC tasks, with Delayed Match and Non-Match to Sample tasks showing the greatest effect size among OFC tasks and Self-Ordered Pointing Task showing the greatest effect size among DLPFC tasks. A functional magnetic resonance imaging study was conducted in parallel to probe the neural underpinnings of age differences in OFC function using the Delayed Match and Non-Match to Sample paradigm. Young but not old adults showed the expected OFC activation. Older compared with young adults showed greater activation in association with successful performance for several posterior regions, perhaps indicating compensation in the face of OFC deficits. Together, these findings indicate a vulnerability of the OFC to age-related decline in brain structure and function. Future studies using new in vivo imaging probes will help determine whether neuropathologic changes underlie the structural and functional changes.