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)
Institute
National Institute on Aging (NIA)
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
2014-07-16
Budget End
2019-12-31
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
Karch, Celeste M; Hernández, Damián; Wang, Jen-Chyong et al. (2018) Human fibroblast and stem cell resource from the Dominantly Inherited Alzheimer Network. Alzheimers Res Ther 10:69
Day, Gregory S; Gordon, Brian A; Perrin, Richard J et al. (2018) In vivo [18F]-AV-1451 tau-PET imaging in sporadic Creutzfeldt-Jakob disease. Neurology 90:e896-e906
Oxtoby, Neil P; Young, Alexandra L; Cash, David M et al. (2018) Data-driven models of dominantly-inherited Alzheimer's disease progression. Brain 141:1529-1544
Chhatwal, Jasmeer P; Schultz, Aaron P; Johnson, Keith A et al. (2018) Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing. Brain 141:1486-1500
Franzmeier, Nicolai; Düzel, Emrah; Jessen, Frank et al. (2018) Left frontal hub connectivity delays cognitive impairment in autosomal-dominant and sporadic Alzheimer's disease. Brain 141:1186-1200
Hsu, Simon; Gordon, Brian A; Hornbeck, Russ et al. (2018) Discovery and validation of autosomal dominant Alzheimer's disease mutations. Alzheimers Res Ther 10:67
Wang, Guoqiao; Berry, Scott; Xiong, Chengjie et al. (2018) A novel cognitive disease progression model for clinical trials in autosomal-dominant Alzheimer's disease. Stat Med 37:3047-3055
Gordon, Brian A; Blazey, Tyler M; Su, Yi et al. (2018) Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study. Lancet Neurol 17:241-250
Stout, Sarah H; Babulal, Ganesh M; Ma, Chunyu et al. (2018) Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers. Alzheimers Dement 14:610-616
Villeneuve, Sylvia; Vogel, Jacob W; Gonneaud, Julie et al. (2018) Proximity to Parental Symptom Onset and Amyloid-? Burden in Sporadic Alzheimer Disease. JAMA Neurol 75:608-619

Showing the most recent 10 out of 59 publications