Our goals are: 1. To describe the course of differential brain aging with a focus on the best-case-scenario naturalistic study of successful aging. The proposed study will complement existing large-scale longitudinal investigations of typical geriatric samples. Our objective is to examine the closest approximation to successful physiological aging to be found in an uncontrolled human population. 2. To gain insights into mechanisms of age-related differential brain shrinkage by examining changes in microstructure of the white matter and indirect indices of basal metabolism in the gray matter. We plan to examine whether regional brain shrinkage is associated with reduced integrity of the underlymg white matter and reduced local vascular activity. We wil assess white matter integrity by measuring the extent of leukoaraiosis and by gauging intactness of the myelinated fibers through diffusion tensor (DTI) and magnetization transfer (MT) imaging. Local vascular changes will be assessed by measuring local T2* relaxation constants that are related to the degree of blood oxygenation. We will introduce new imaging method - multi-echo Susceptibility Weighted Imaging (SWI) that allow measurement of T2* and local field variations with better precision and resolution that by conventional gradient-recall methods. 3 To evaluate the links between age-related regional brain changes (volume, diffusion and magnetization properties, and basal metabolism) and performance in three cognitive domains with known vulnerability to aging: episodic memory, executive functions, and speed of processing. 4. To examine the effect of modifiers of brain and cognitive aging - the vascular risk and genetic factors on differential brain and cognitive aging. By examining the possibility of dose-response effect of vascular risk factors on adult brain and cognition we hope to provide the data against which pathology will be understood. Because some of the women who participate in the study will be on hormone replacement therapy (HRT), we will assess the potential benefits of HRT on brain aging. The modifying role of ApoE genotype in shaping the trafectories of brain and cognitive againg will be also assessed. 5. Finally, common to all listed aims is a longitudinal approach to study of biological and cognitive change. To attain that overriding goal, we plan to apply longitudinal latent-variable growth modeling techniques to the analysis of our data. The innovative aspect of that approach is that those techniques are the staple of demographic, social, and cognitive aging studies. We expect these modeling techniques will allow testing hypotheses about relations between regional brain changes and specific cognitive skills in healthy aging adults. ? ?
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