Gerontological Nursing Interventions Research Center (GNIRC)

Title: Genotype-Phenotype Correlations in Persons with Alzheimer's Disease
Principal Investigator: Debra Schutte, PhD, RN
Study Site: The University of Iowa

Abstract
Alzheimer disease (AD) is a common neurodegenerative disorder. The clinical phenotype in AD is characterized by progressive deterioration in cognitive ability that interferes with social and occupational performance. While the clinical AD phenotype includes impaired cognition, function, and behavior, individual variability exists in the rate, pattern, and specific domains of impairment. Research to explore the link between genetic variants and AD natural history is critical to the development of genotype-directed interventions. Several susceptibility genes are associated with increasing one's risk for developing AD and are thus candidates for explaining phenotypic differences. This application proposes a pilot genotype-phenotype correlation study to explore the relationship between variations in candidate AD susceptibility genes and cognition, function, and behavior among persons with moderate to advanced AD. Persons diagnosed with AD will be recruited from five long-term care facilities. Following phelebotomy, DNA will be isolated and genotyped for known variants within several candidate genes. Subjects with AD will complete a phenotype battery consisting of established measures of cognition, function, and behavior at baseline, 4 months, and 8 months. In addition to refining recruitment and data collectionn strategies for the implementation of a future, large, prospective genotype-phenotype correlation study, the specific aims of this pilot study are to: 1) describe the distribution of AD susceptibility allele frequencies in this sample compared to healthy controls, 2) describe the cognitive, functional, and behavioral characteristics of persons with advanced AD, and 3) describe the relationship between variations in genotype and variations in cognitive status, functional ability, and behavior.