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.
|Panizzon, Matthew S; Hauger, Richard L; Xian, Hong et al. (2018) Interactive effects of testosterone and cortisol on hippocampal volume and episodic memory in middle-aged men. Psychoneuroendocrinology 91:115-122|
|Hatton, Sean N; Panizzon, Matthew S; Vuoksimaa, Eero et al. (2018) Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age. Hum Brain Mapp 39:2235-2245|
|Logue, Mark W; Panizzon, Matthew S; Elman, Jeremy A et al. (2018) Use of an Alzheimer's disease polygenic risk score to identify mild cognitive impairment in adults in their 50s. Mol Psychiatry :|
|Elman, Jeremy A; Panizzon, Matthew S; Gillespie, Nathan A et al. (2018) Genetic architecture of hippocampal subfields on standard resolution MRI: How the parts relate to the whole. Hum Brain Mapp :|
|Gillespie, Nathan A; Neale, Michael C; Bates, Timothy C et al. (2018) Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addiction :|
|Elman, Jeremy A; Jak, Amy J; Panizzon, Matthew S et al. (2018) Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects. Alzheimers Dement (Amst) 10:372-381|
|Gustavson, Daniel E; Panizzon, Matthew S; Franz, Carol E et al. (2018) Genetic and environmental architecture of executive functions in midlife. Neuropsychology 32:18-30|
|Gustavson, Daniel E; Panizzon, Matthew S; Elman, Jeremy A et al. (2018) Genetic and Environmental Influences on Verbal Fluency in Middle Age: A Longitudinal Twin Study. Behav Genet :|
|Gustavson, Daniel E; Panizzon, Matthew S; Elman, Jeremy A et al. (2018) Stability of genetic and environmental influences on executive functions in midlife. Psychol Aging 33:219-231|
|Hatton, Sean N; Franz, Carol E; Elman, Jeremy A et al. (2018) Negative fateful life events in midlife and advanced predicted brain aging. Neurobiol Aging 67:1-9|
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