Purpose. The goal of this FOA is to advance the discovery of new, efficacious therapies for the treatment, delay of progression, or prevention of Alzheimers disease (AD), mild cognitive impairment (MCI) and age-related cognitive decline. This FOA encourages the early stages of drug discovery necessary to identify promising disease-modifying therapies as well as treatments aimed at ameliorating the cognitive and neuropsychiatric/behavioral symptoms characteristic of Alzheimers disease. Studies aimed at the discovery and testing of therapies directed at a variety of established as well as novel therapeutic targets are encouraged. The goal is not to duplicate or compete with pharmaceutical companies but to encourage the process of discovering new, innovative, and effective therapeutics for the prevention and treatment of the cognitive impairment and behavioral symptoms associated with Alzheimer's disease Mechanism of Support. This FOA will use the NIH Exploratory/Developmental (R21) award mechanism. Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the quality, duration, and costs of the applications received.