This application is for an NIH K01 Mentored Research Scientist Development Award where I will gain the xpertise necessary to establish myself as an independent investigator exploring the neurobiology underlying cognitive aging. I will receive training in a specific approach to investigating the neurobiological underpinnings of cognitive aging with the combined use of psychopharmacological manipulations of cognition and functional magnetic resonance imaging (fMRI) from two established experts in these fields, Paul Newhouse, M.D. and Andrew Saykin, Psy.D. Under the mentorship of Drs. Newhouse and Saykin, I will participate in on-site residencies, tutorials, courses, and hands-on research projects. This training will provide me with unique expertise as I combine my prior training in cognitive psychology with the ability to utilize the cutting edge combination of psychopharmacological manipulations and fMRI to study the neurobiology of cognitive aging. As an integral part of my training I will conduct two pharmacological fMRI studies that will extend my findings showing the importance of cholinergic integrity in observing effects of estrogen on cognition. Study 1 will test the hypothesis that neural compensation that is observed when older women activate more frontal relative to occipital cortex is modulated by cholinergic integrity and estrogen treatment. Study 2 will test the hypothesis that aging of the cholinergic system is principally responsible for age-associated neural compensation seen in attention, working memory, and episodic memory tasks. Study 2 will also use estrogen to modulate cholinergic-related cognitive processes. These studies will be the first to combine the powerful manipulations of cholinergic pharmacological challenge, sex hormone treatment, and fMRI to examine the neurotransmitter-hormone interaction effect on cognition. The results of these studies will provide evidence for the importance of cholinergic integrity and estrogen treatment on brain and cognitive functioning in older women. Understanding the neurobiology underlying the estrogen effect on cognition is important for the future development of treatment strategies for age-related cognitive dysfunction.

Public Health Relevance

These studies will emphasize the importance of knowledge of the neurobiology underlying cognitive aging for the furure design of clinical interventions. The results will also be important for an understanding why prior trials of estrogen effects on cognition have failed because cholinergic systems in older women were impaired such that no positive effects of estrogen were seen.

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)
Program Officer
Wagster, Molly V
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University of Vermont & St Agric College
Schools of Medicine
United States
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Dumas, Julie A; Filippi, Christopher G; Newhouse, Paul A et al. (2017) Dopaminergic contributions to working memory-related brain activation in postmenopausal women. Menopause 24:163-170
Dumas, Julie A; Newhouse, Paul A (2015) Impaired working memory in geriatric depression: an FMRI study. Am J Geriatr Psychiatry 23:433-6
Dumas, Julie A; Kutz, Amanda M; McDonald, Brenna C et al. (2013) Increased working memory-related brain activity in middle-aged women with cognitive complaints. Neurobiol Aging 34:1145-7
Dumas, Julie A (2013) Lifetime hormone exposure and cognition in postmenopausal women with breast cancer. Menopause 20:883-5
Dumas, Julie A; Makarewicz, Jenna; Schaubhut, Geoffrey J et al. (2013) Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study. Brain Imaging Behav 7:524-32
Newhouse, Paul; Albert, Kimberly; Astur, Robert et al. (2013) Tamoxifen improves cholinergically modulated cognitive performance in postmenopausal women. Neuropsychopharmacology 38:2632-43
Dumas, Julie A; Albert, Kimberly M; Naylor, Magdalena R et al. (2012) The effects of age and estrogen on stress responsivity in older women. Am J Geriatr Psychiatry 20:734-43
Dumas, Julie A; Kutz, Amanda M; Naylor, Magdalena R et al. (2012) Estradiol treatment altered anticholinergic-related brain activation during working memory in postmenopausal women. Neuroimage 60:1394-403
Newhouse, Paul A; Potter, Alexandra S; Dumas, Julie A et al. (2011) Functional brain imaging of nicotinic effects on higher cognitive processes. Biochem Pharmacol 82:943-51
Dumas, Julie A; Newhouse, Paul A (2011) The cholinergic hypothesis of cognitive aging revisited again: cholinergic functional compensation. Pharmacol Biochem Behav 99:254-61

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