DESCRIPTION (provided by applicant): The purpose of the proposed R03 pilot study is to longitudinally examine the relationship between apolipoprotein E (APOE) polymorphisms and cognitive functioning among individuals with mild cognitive impairment (MCI). Specific APOE genotypes (i.e., e4 allele) pose a risk for Alzheimer's disease (AD), while other polymorphisms are neuroprotective (i.e., s2 allele). Some current data supports a cognitive phenotype associated with specific APOE genotypes. However, most studies have failed to consider cognitive domains other than memory or the neuroprotective properties of the e2 allele. In light of recent revisions to MCI research diagnostic criteria, MCI subtypes may have different associations with the APOE genotype. However, the relationship between MCI subtypes and APOE genotype remains uninvestigated. The proposed R03 pilot study utilizes archival data from the Boston University Alzheimer's Disease Core Center (BU ADCC) Clinical Core registry. Approximately 435 geriatric participants (n=245 normal controls (NC), n=190 MCI participants) have undergone thorough neurodiagnostic workup, including a comprehensive neuropsychological protocol. Three-year follow-up data exist on approximately 88% of the sample. The proposed study employs a longitudinal cross-sectional design that stratifies participants according to APOE genotype status (i.e., s2, e3, and e4 allele carriers) and diagnostic category (i.e., NC, all MCI participants, MCI subtypes). The BU ADCC registry database offers a rich resource to address the aims of the proposed pilot study which include: (1) characterizing cognitive associations of the APOE genotype, and (2) exploring the cognitive phenotype of the APOE genotype among MCI subtypes. Data from this study will shed light on the associations between specific MCI subtypes and a genetic risk factor for AD by identifying MCI subtypes, if any, with accelerated cognitive changes over the three-year follow-up period. This information may be applied in clinical evaluations of patients with MCI to formulate prognostic impressions. Furthermore, findings from the proposed pilot study will generate feasibility data for developing a future, large-scale neurogenetics research study.