2008 AFAR Research Grant: Estrogen Attenuation of Cholinergic-Induced Alterations in Fronto-Parietal Brain Activation during Working Memory in Older Women

Please give a brief summary of your AFAR research project.
Studies have suggested that changes that occur in mental abilities as we age may be a result of chemical changes that occur in the brain. The loss of estrogen that occurs after menopause in women may accelerate this change. This study is designed to test whether giving the hormone estrogen will affect the system of the brain that uses acetylcholine. Acetylcholine is a naturally occurring chemical in the brain that has been shown to be associated with attention and memory. This study will ass the functioning of the cholinergic system and its interaction with estrogen using functional magnetic resonance imaging (fMRI). This study involves administering estrogen and then giving cholinergic medications that temporarily affect the ability to perform a working memory task. Overall, this study will examine how estrogen administration changes the negative effects of the cholinergic drugs and therefore may act to alter the effects of aging on brain functioning.

What problems are you addressing and what specific questions will your research seek to answer?
This study will examine the neurobiology underlying cognitive aging. Prior studies have assessed the functional neuroanatomy affected by aging but these studies do not provide information about the neurobiological mechanisms that change with age. This study will address the following questions. How does estrogen treatment modify brain cholinergic systems that are responsible for cognitive processing? Can estrogen provide a protective effect on brain cholinergic systems? Can this interaction be observed with functional neuroimaging?

What aspects of your project are most interesting from a scientific point of view?
The most interesting part of this study will be that it will provide information about a neurobiological process that affects cognition and is sensitive to aging. No study thus far has combined the methodologies with questions from cognitive aging research to answer the questions proposed by this study.

What are the implications of your research for age-related diseases and disorders?
The results of these studies on the estrogen-cholinergic interaction will provide a link to a neurobiological mechanism for age effects on cognition. My prior work shows that the integrity of the cholinergic system is critical for observing a beneficial effect of estrogen on cognition and suggests that hormonal support of cholinergic functioning may be a critical element in age-related compensation for cognitive problems. As women continue to take estrogen for management of menopausal symptoms, it is important to understand the neurobiology underlying the estrogen effect on cognition for the future development of prevention and treatment strategies for age-related diseases and for understanding normal cognitive aging.

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