In this K01 application, Kathleen Hayden PhD is seeking training in genetics with a goal of exploring cognitive endophenotypes (latent or sub-clinical phenotypes representing the underlying disease genotype) of Alzheimer disease (AD) to inform ongoing and future genetic studies. The project builds on the candidate's prior work and is focused on providing advanced expertise in the area of genetics in order to facilitate her development as an independent researcher. The plan leverages the research environment and ample resources of the Bryan Alzheimer's Disease Research Center (Bryan ADRC) and its partners, the Duke Institute for Genome Sciences and Policy (IGSP), the Center for the Study of Aging, and the Department of Biostatistics and Bioinformatics. The research plan in this application is focused on advancing methodology to enhance the detection of yet to be determined risk genes involved in AD. This application proposes to use samples from four large NIH funded studies which have all been harmonized in their clinical data collection methodologies (Cache County Memory Study, Bryan ADRC cohorts, NAS-NRC Twin Study, and the Neurocognitive Outcomes of Depression in the Elderly Study) to rigorously determine AD endophenotypes using hypothesis driven and empirically based statistical approaches. Guided by Mentors, Kathleen Welsh-Bohmer (Bryan ADRC &CCMS PI) and David Goldstein (Director of Population Genomics &Pharmacogenetics IGSP) the candidate's career development plan will also benefit from the input of collaborators Carl Pieper (biostatistics), Brenda Plassman (twin studies), and David Steffens (geriatric depression) as she strives to understand and develop latent models within the unique cohorts: The training program includes coursework in latent class analysis, latent class trajectories, genetics, and computational biology as well as experiential training in neuropsychological methods, genetic study design, and statistical approaches unique to genetic methodologies. This relevant and timely application addresses a need to apply endophenotyping methods to population genetic work. Ultimately the application of endophenotypes of AD will facilitate the identification of new genes, highlight potential causal pathways of disease, and suggest avenues for future treatment development.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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National Institute on Aging Initial Review Group (NIA)
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Miller, Marilyn
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Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
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Hayden, Kathleen M; Kuchibhatla, Maragatha; Romero, Heather R et al. (2014) Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile approach. Am J Geriatr Psychiatry 22:1364-74
Hayden, Kathleen M; Makeeva, Oksana A; Newby, L Kristin et al. (2014) A comparison of neuropsychological performance between US and Russia: preparing for a global clinical trial. Alzheimers Dement 10:760-768.e1
Hayden, Kathleen M; McEvoy, Jill M; Linnertz, Colton et al. (2012) A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in aging. Alzheimers Dement 8:381-8
Mayeux, Richard; Reitz, Christiane; Brickman, Adam M et al. (2011) Operationalizing diagnostic criteria for Alzheimer's disease and other age-related cognitive impairment-Part 1. Alzheimers Dement 7:15-34
Hayden, Kathleen M; Jones, Richard N; Zimmer, Catherine et al. (2011) Factor structure of the National Alzheimer's Coordinating Centers uniform dataset neuropsychological battery: an evaluation of invariance between and within groups over time. Alzheimer Dis Assoc Disord 25:128-37
Hayden, Kathleen M; Reed, Bruce R; Manly, Jennifer J et al. (2011) Cognitive decline in the elderly: an analysis of population heterogeneity. Age Ageing 40:684-9
Hayden, Kathleen M; Zandi, Peter P; West, Nancy A et al. (2009) Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study. Arch Neurol 66:1378-83
Levin, Edward D; Aschner, Michael; Heberlein, Ulrike et al. (2009) Genetic aspects of behavioral neurotoxicology. Neurotoxicology 30:741-53