Aging is the single greatest risk factor for the development of many neurodegenerative disorders, including Alzheimers disease. However, defining the features of brain aging, distinct from disease, that mediate poor neurocognitive outcomes has proved challenging on the basis of human investigation. A prominent focus of our current research in nonhuman primate models aims to test the possibility that cognitive aging is associated with a distributed pattern of altered functional connectivity in critical cortical networks. These studies comprise a collaborative effort between the Comparative Medicine Section of the NIA-IRP and investigator at the National Institute on Drug Abuse. Subjects included young adult (12 years of age) and old rhesus monkeys (25 years) previously tested on a battery of tasks sensitive to aging, including tests of spatiotemporal working memory that require the dorsolateral prefrontal cortex, and an object recognition task dependent on medial temporal lobe integrity. Subjects were lightly anesthetized using a protocol previously shown to preserve resting state BOLD signal (i.e., 0.5 to 1.0% isoflurane and dexmedetomidine), and scanning was carried out on a 3T Siemens Trio scanner. Vital physiological parameters (i.e., blood pressure, oxygen saturation, heart rate, etc.) were monitored continuously. Following stabilization and acquisition of T1-weighted structural scans for localization, six whole brain resting state Echo Planar Imaging volumes were acquired (5 minutes each, steps = 200, tr = 1.7s) over a total of 30 minutes. Resting state scans were pre-processed using established pipelines and co-registered to the D99 macaque template using AFNI. Independent component analysis was performed using FSL. Seed based analyses were performed using a major hub of the default mode network (the posterior cingulate cortex), and a region strongly implicated cognitive aging (the dorsolateral prefrontal cortex). For both seeds, aged monkeys displayed changes in functional connectivity relative to young subjects distributed across multiple cortical areas, including temporal, insular, frontal and anterior cingulate regions, many involving age-related increases in connectivity. These findings extend our observations in rats to the primate brain and provide evidence consistent with the possibility that late life changes in cortical network dynamics are among the factors that render aging a key risk for the development of neurodegenerative disease. The results will be reported at this year's Society for Neuroscience meeting.
Showing the most recent 10 out of 15 publications
