Alzheimer's disease (AD) is the most common cause of dementia in adults over the age of 65 in the United States (Evans, 1990). AD is a debilitating disease and has devastating psychological and financial effects on patients, caregivers, families, and society. Early detection is essential to successful treatment (Solomon &Murphy, 2005). Early deficits often involve memory (Salmon &Bondi, 1999), an important topic of study due to its necessary presence in AD diagnosis and its significant impact on functioning. Medial temporal lobe (MTL) structures are involved in the encoding of new information into memory (Squire, 1992) and have been identified as those initially affected by AD neuropathology (Braak &Braak, 1991;Jack et al., 1992). Mild cognitive impairment (Petersen et al., 1999;Tierney et al., 1996) and the epsilon 4 allele for apolipoprotein E (APOE) have been associated with increased risk for AD (Corder et al., 1993). Thus, a long-term objective of this proposal is to develop a program of study using arterial spin labeling (ASL) magnetic resonance imaging (MRI) techniques to examine (a) the response of MTL subregions during encoding in individuals at risk for AD and (b) develop reliable strategies for early identification of these individuals so that they may be targeted for treatments as they are developed. A specific aim of this project is to use ASL MRI in order to expand upon previous findings from other imaging modalities and examine the brain activation patterns of nondemented older adults at rest and during memory encoding. In addition, this project aims to assess MTL morphometry of nondemented older adults. These specific aims will be achieved through group comparison methodologies comparing structural integrity, brain response, cognitive performance, and interactions between these variables. These variables will be compared between older adults at risk for developing AD and a matched sample of older adults not at risk. Standardized instruments assessing learning, memory, and executive functioning will be completed. Multiple regression and- correlation analyses will be employed to assess the relation of cognitive performance with AD risk, structural integrity, and brain activation patterns. The proposed research project has significant relevance to public health. AD affects every segment of society and is a growing public health concern due to the increasing longevity of the U.S. population. It is estimated that the prevalence of AD in the U.S. will increase from its current estimate of 4.5 million people to approximately 11.3 to 16 million people by 2050 (Hebertetal 2003). Results from the proposed project may aid in identifying additional factors contributing to increased risk for developing AD thereby improving early detection and targeting individuals for early intervention.