The symptom domains of greatest interest in Alzheimer's disease (AD), cognition, function, and behavior, are also associated with executive function (EF). But EF cannot be directly observed;these symptom domains and EF have unknown measurement error in their assessment, and unknown interrelationships. Precise assessment of each area is important for efficient clinical studies of AD interventions and for public health purposes like screening for AD and dementia. Unlike regression analysis, latent variable analysis (LVA) methods can increase precision by explicitly modeling measurement error, and can model constructs (like EF) that are not directly observable. Additional precision will be derived from determining whether EF contributes significant explanatory power to models of cognitive aging and AD. This K01 therefore has two specific aims.
Aim 1 : Model measurement error in instruments that are common in clinical trials for AD using a Bayesian Network to differentiate measurement error from true change for non-demented elderly, persons with AD, and persons with incipient AD.
Aim 2 : Construct a statistical model of EF for persons with AD and cognitively normal elderly controls in order to: a. evaluate the latent factor structure in EF;and b. compare fits of latent variable models of EF. The best fitting model will address the hypothesis that EF contributes significant explanatory power for variance in cognitive, functional and behavioral symptoms and will suggest whether this is true for both normal elderly and persons with AD.
These aims will contribute to precision and modeling of assessment in normal aging and AD;and to a better understanding of EF as an outcome in aging research and clinical studies of AD. The proposed K01 will develop deep and broad sets of skills in assessment and analysis, to be achieved with training in design and conduct of clinical trials, measurement theory, neuropsychology, and advanced statistical/LVA modeling. Mentoring from an experienced clinical trialist, Paul Aisen, MD, will be supplemented with expert consultation in these domains throughout the five year grant. The PI is a junior investigator in who wishes to extend her expertise in statistics to include LVA methods, and her background in cognitive science to include neuropsychological assessment and measurement. This K01 award will achieve these and so will move the PI closer to her long-term goal of becoming an independent researcher in cognitive aging and AD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AG027172-04
Application #
7646198
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Wagster, Molly V
Project Start
2006-09-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$126,090
Indirect Cost
Name
Georgetown University
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Tractenberg, Rochelle E; Yumoto, Futoshi; Aisen, Paul S et al. (2012) Using the Guttman scale to define and estimate measurement error in items over time: the case of cognitive decline and the meaning of ""points lost"". PLoS One 7:e30019
Tractenberg, Rochelle E; Pietrzak, Robert H (2011) Intra-individual variability in Alzheimer's disease and cognitive aging: definitions, context, and effect sizes. PLoS One 6:e16973
Tractenberg, Rochelle E (2010) Classical and modern measurement theories, patient reports, and clinical outcomes. Contemp Clin Trials 31:1-3
Tractenberg, Rochelle E; Yumoto, Futoshi; Jin, Shelia et al. (2010) Sample size requirements for training to a kappa agreement criterion on clinical dementia ratings. Alzheimer Dis Assoc Disord 24:264-8
Tractenberg, Rochelle E; Aisen, Paul S; Hancock, Gregory R et al. (2009) No cross-sectional influence of APOE epsilon4 dose on clinical tests in Alzheimer's disease. Neurobiol Aging 30:1327-8
Tractenberg, R E (2009) Analytic methods for factors, dimensions and endpoints in clinical trials for Alzheimer's disease. J Nutr Health Aging 13:249-55
Tractenberg, Rochelle E; Aisen, Paul S (2009) Agreement in cognitive and clinical assessments in Alzheimer's disease. Dement Geriatr Cogn Disord 27:344-52
Nissman, Steven A; Tractenberg, Rochelle E; Babbar-Goel, Anita et al. (2008) Oral gabapentin for the treatment of postoperative pain after photorefractive keratectomy. Am J Ophthalmol 145:623-629
Tractenberg, R E; Singer, C M (2007) Sleep and sleep disturbance: from genes to dreams. Cell Mol Life Sci 64:1171-3