Neuroimaging and Functional Senscence in Aging

Makris, Nikolaos

Abstract

The rhesus monkey is an excellent model for studies of normal aging since brain organization and cognitive capacity are quite similar to humans and the monkey does not get Alzheimer's disease. Additionally monkeys can be studied under controlled conditions, behavioral assessment can be done prior to death and the brain can be optimally preserved without post-mortem delay. Such studies demonstrate age- related cognitive decline with preservation of neurons and synapses but loss and damage to white matter and volumetric loss of white matter in standard MRI scans. But, it is not clear whether loss or damage to myelin is diffuse or localized to specific pathways. Since breakdown in myelin correlates with cognitive decline, it is probably that disruption of corticocortical fiber tracts my contribute to age-related cognitive impairments. A new neuroimaging method, Diffusion Tensor MRI (DT- MRI) has been used for in vivo identification and measurement of long white tracts in the human brain but a major limitation on interpretation of the DT-MRI in humans is the difficulty of validation by post-mortem examination of white matter tracts because of post-mortem delay and immersion fixation. This proposed pilot investigation will adapt to the monkey brain this new DT-MRI method to identify and quantify white matter tracts in young and old monkeys. These monkeys are available to us from an NIH funded Program Project grant which collects behavioral measures of cognitive performance, neurophysiological measures of conduction velocity and then prepares whole hemisphere serial brain sections. These data and spare series of sections will be available for comparisons with the CT-MRI data on specific fiber tracts. To determine their """"""""functional"""""""" significance the long corticocortical association pathways will be identified, quantified and age-related changes in volume determined and then correlated with the behavioral and neurophysiological data of the DT-MRI observations. In addition spare series of histological sections will be used to validate the DT-MRI observations with actual white matter and provide the pilot data necessary to seek funding for additional DT-MRI studies of normal aging in both monkeys and humans.