We are part of a large population-based study of brain aging and incident dementia in the Seattle metropolitan area called the Adult Changes in Thought (ACT) study, directed by Dr. Eric Larson. Our part of this large project is to characterize structural and biochemical changes that accompany brain aging and neurodegeneration, and then relate these to cognitive performance. A major focus of this work is to discover commonly used therapeutics that may retard one of the several disease processes that can lead to dementia. This project relies heavily on analytical biochemistry to investigate protein modifications and free radical damage to specific tissue elements. In addition, immunohistochemical and stereological techniques are used to characterize specific pathways of neurodegeneration.