The scientific objective of establishing an international network for identification, evaluation, and longitudinal follow-up of families with early onset dominantly inherited Alzheimer's disease (AD) is addressed in the overview of this renewal application and in Core B: Clinical. The activities of the Core C: Biostatistics are designed to enhance the research objectives of DIAN by serving the DIAN investigators with a smooth transition from the database to statistical analyses, providing appropriate statistical analysis resources to all Cores, and developing necessary longitudinal statistical models to test the preclinical hypotheses of DIAN on all major biomarkers of AD. The major hypotheses in DIAN conjecture a period of preclinical AD in individuals who are destined to develop early onset dementia (mutation carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early onset dementia (noncarriers) and a temporal difference in preclinical changes across these correlates for mutation carriers. The methodological significance of the hypothesis is the requirement of state-of-the-art longitudinal statistical models to adequately estimate and compare the longitudinal rates of change on multi-modal disease markers during the preclinical period, and to assess their association with the risk of subsequent development of symptomatic AD.

Public Health Relevance

In the proposed DIAN renewal, Core C: Biostatistics Core will bridge the transition from the DIAN database stored and managed by Core H: Informatics Core to the analyses of the longitudinal as well as cross-sectional data. Specifically, the Biostatistics Core will oversee the statistical quality control of data and appropriate data analyses for the study by producing appropriately de-identified and statistically analyzable datasets for distribution/analysis and leading the statistical data analyses for all Cores.

Agency
National Institute of Health (NIH)
Type
Multi-Year Funded Research Project Cooperative Agreement (UF1)
Project #
2UF1AG032438-07
Application #
8863370
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Xiong, Chengjie; Weng, Hua; Bennett, David A et al. (2014) Subsets of a large cognitive battery better power clinical trials on early stage Alzheimer's disease. Neuroepidemiology 43:131-9
Dobrowolska, Justyna A; Kasten, Tom; Huang, Yafei et al. (2014) Diurnal patterns of soluble amyloid precursor protein metabolites in the human central nervous system. PLoS One 9:e89998