The purpose of this career development award is to assist me in gaining the knowledge and experience necessary to become a successful, independent investigator in multidisciplinary aging research. Over the course of the four year award period I will obtain formal training in the development of an integrative aging research program (Training Goal 1), as well as learn the principles and methods of two disciplines that I believe are critical to studying the genetics of cognitive and biological aging: molecular genetics (Training Goal 2) and neuroendocrinology (Training Goal 3). The Department of Psychiatry at the University of California San Diego is an ideal setting for this project, because it possesses several well-established aging research programs, a world-class faculty, and numerous state-of-the-field scientific resources. It is fully committed to my career development. As a clinically trained neuropsychologist with experience in the use of the twin method to study neurocognitive phenotypes, I am uniquely positioned to benefit from this additional training, and in doing so accomplish my goal of developing an integrative cognitive and brain aging research program. The scientific component of this proposal will examine the genetic factors that regulate the relationships among testosterone (T) and aging-related changes in cognition, brain, and health. T declines with increasing age, and has been associated with multiple cognitive, brain, and health-related aging phenotypes. I hypothesize that the effects of T differ as a function of the number of trinucleotide (CAG) repeats in the androgen receptor (AR) gene. There is a critical knowledge gap in understanding the impact of this variation in the AR gene and other T-related genes on the relationships among T, cognition, brain, and health. With data from two genetically informative samples with similar cognitive, neuroimaging, health, and endocrine data (the Vietnam Era Twin Study of Aging and the Baltimore Longitudinal Study of Aging) I will be able to fill this knowledge gap.
The specific aims are: 1) Characterize how variation in the AR gene influences androgen- and age-sensitive phenotypes;2) Elucidate the extent to which variation in the AR gene affects other genetic determinants of androgen- and age-sensitive phenotypes;and 3) Determine whether T and variation in the AR gene predict changes in cognition, brain, and health over time. Innovative aspects of this proposal are that it sets the stage for a genetically informed, personalized medicine approach to treating T deficiency by focusing on the T-AR gene interaction;it translates and extends findings from primarily animal studies into humans;and it examines aging-related changes beginning in mid-life, prior to the onset of disease, rather than in old age. Relevance: By elucidating the genetic factors that regulate the relationships among testosterone (T), cognition, brain, and health in aging men, this study will shed new light on the function of T, as well as identify individuals most susceptible to age-related changes in T and most likely to benefit from hormone therapy.
By elucidating the genetic factors that regulate the relationships among testosterone (T), cognition, brain, and health in aging men, this study will shed new light on the function of T, as well as identify individuals most susceptible to age-related changes in T and most likely to benefit from hormone therapy.
|Vuoksimaa, Eero; Panizzon, Matthew S; Hagler Jr, Donald J et al. (2016) Heritability of white matter microstructure in late middle age: A twin study of tract-based fractional anisotropy and absolute diffusivity indices. Hum Brain Mapp :|
|Walhovd, Kristine B; Krogsrud, Stine K; Amlien, Inge K et al. (2016) Neurodevelopmental origins of lifespan changes in brain and cognition. Proc Natl Acad Sci U S A 113:9357-62|
|Fennema-Notestine, Christine; McEvoy, Linda K; Notestine, Randy et al. (2016) White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure. Neuroimage Clin 12:737-745|
|Vuoksimaa, Eero; Panizzon, Matthew S; Chen, Chi-Hua et al. (2016) Is bigger always better? The importance of cortical configuration with respect to cognitive ability. Neuroimage 129:356-66|
|Kremen, William S; Panizzon, Matthew S; Cannon, Tyrone D (2016) Genetics and neuropsychology: A merger whose time has come. Neuropsychology 30:1-5|
|Panizzon, Matthew S; Neale, Michael C; Docherty, Anna R et al. (2015) Genetic and environmental architecture of changes in episodic memory from middle to late middle age. Psychol Aging 30:286-300|
|Prom-Wormley, Elizabeth; Maes, Hermine H M; Schmitt, J Eric et al. (2015) Genetic and environmental contributions to the relationships between brain structure and average lifetime cigarette use. Behav Genet 45:157-70|
|Panizzon, Matthew S; Hauger, Richard L; Sailors, Megan et al. (2015) A new look at the genetic and environmental coherence of metabolic syndrome components. Obesity (Silver Spring) 23:2499-507|
|Vuoksimaa, Eero; Panizzon, Matthew S; Chen, Chi-Hua et al. (2015) The Genetic Association Between Neocortical Volume and General Cognitive Ability Is Driven by Global Surface Area Rather Than Thickness. Cereb Cortex 25:2127-37|
|Docherty, Anna R; Hagler Jr, Donald J; Panizzon, Matthew S et al. (2015) Does degree of gyrification underlie the phenotypic and genetic associations between cortical surface area and cognitive ability? Neuroimage 106:154-60|
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