The overall goal of the Religious Orders Study Core is to continue to facilitate externally funded high quality research on Alzheimer's disease and related disorders. The Core supports a variety of studies by investigators at Rush and across the country, including studies of the transition from normality to mild cognitive impairment to Alzheimer's disease; studies linking complex post-mortem findings to change in different cognitive abilities over multiple years prior to death; and studies that explore the biologic mechanisms linking risk factors to post-mortem findings to the clinical manifestations of disease proximate to death. Requests for brain tissue from the Core substantially exceeds its availability. The Core will build on its success during the past funding period and continue recruiting and performing annual evaluations on older members of Catholic Religious Communities without dementia with an emphasis on enrolling African American and Hispanic Catholic clergy. Nearly 850 participants have enrolled. The overall follow-up rate exceeds 98% with up to seven evaluations and the autopsy rate is 90% with 130 brain autopsies out of 145 deaths. The Core supported 22 individual funded projects. Brain tissue from nearly 90% of participants has already been distributed to one or more investigators; 65 cases were distributed to between five and nine investigators, and 16 cases were distributed to more than 10 investigators. The proposed Core provides a plan for ongoing enrollment to ensure that the Core remains a renewable source of clinical data and post-mortem tissue for externally funded studies. The continuation of this Core for five more years will result in up to 12 years of data on more than 1000 persons and brain tissue from about 250 persons. Such a rich and diverse resource will allow the Core to continue to support numerous investigators. It will also offer the Alzheimer's disease research community new opportunities to use clinical pathologic studies in novel ways to understand the complex relation between cognitive decline and progression of pathology. Such studies will require post-mortem tissue from persons who died at all stages of disease with all possible trajectories of cognitive decline prior to death.