In many mammals, including humans and some non-human primate species, the aging brain undergoes a? number of large-scale changes that can be observed with imaging and cognitive approaches. These agerelated? changes include structural atrophy, increased mineral deposition, decline in neurotransmitter? production, periventricular ischemia, decline in glucose metabolism (and concomitant decline in certain higher? cognitive functions, particularly in the domains of memory, cognitive speed, and executive function). The? dramatic effect of diet restriction (DR) to increase lifespan in many species and its salutary effects on? metabolic processes such as oxidative stress, suggest that this intervention may also be good for the brain. In? this project, we propose to test the hypothesis that rhesus monkeys undergoing chronic DR will exhibit less? pronounced age-related brain structural and functional changes than their ad libitum fed age-matched? controls. We propose to test this hypothesis using high-resolution volumetric and microstructural Magnetic? Resonance Imaging (MRI) techniques of the brain and cognitive tests. Our emphasis is on structures and? cognitive functions that may change with age. We plan to accomplish the following specific aims: 1)? determine if baseline differences exist between DR and control animals on tissue volume and integrity such? as regional gray and white matter volume, T2 relaxation time (gray matter mineralization), magnetization? transfer, and diffusion tensor imaging (white matter integrity). 2) determine whether cognitive differences exist? between DR and control groups using computerized non-human primate behavioral paradigms that have? previously been shown to be sensitive to age. 3) determine whether the rate of structural change has been? slowed in the DR group.
These aims will be accomplished utilizing the expertise and excellent resources of? the Wisconsin Primate Research Center and the Keck Laboratory's 3-Tesla MRI. Analyses will examine the? groups for baseline and longitudinal differences. The unique opportunity to study these animals with a? comprehensive MRI imaging and cognitive battery should provide much needed information regarding global? aging processes in the brain, and extend the evaluation of the effects of the DR intervention in domains of? great significance to humans.
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