Middle-aged children of persons with Alzheimer's disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer's Prevention.

Adult children of persons with Alzheimer's disease are at increased risk of developing Alzheimer's disease because of hereditary, environmental, and health risk factors shared with affected parents. The Wisconsin Registry for Alzheimer's Prevention (WRAP) has completed baseline assessments on 452 middle-aged persons (mean = 53 years) who have at least 1 parent with AD. Forty-five percent had 1 or more apolipoprotein (APOE) epsilon4 alleles. There were few significant differences between epsilon4 carriers and noncarriers in demographics, health, and lifestyle measures or in neuropsychological performance. The high percentage of WRAP participants who are carriers of APOE epsilon4 underscores their increased risk for developing Alzheimer's disease, but the absence of differences related to APOE status and high mean scores on cognitive tests suggests that the APOE epsilon4 gene has yet to have a clinical impact on cognitive functioning. The WRAP cohort may be a valuable group to follow prospectively to characterize the nature of cognitive change in relation to risk factors and to identify underlying preclinical neurobiological changes.