Arousal-Induced Memory Selectivity in Aging and Alzheimer's Disease

Sara Gallant, PhD
University of Southern California (Los Angeles, CA)

Mentors

Mara Mather, PhD
University of Southern California (Los Angeles, CA)
Year Awarded:
2018
Grant Duration:
July 1, 2018 to June 30, 2020
Disease:
Alzheimer's Disease
Award Amount:
$150,000
Grant Reference ID:
A2018449F
Award Type:
Postdoctoral Fellowship
Award Region:
US Southwestern

This grant is made possible in part by support from Alzheimer’s Los Angeles.

Sara Gallant, PhD

The Locus Coeruleus and Memory Selectivity in Aging and Alzheimer's Disease

Summary

The ability to selectively remember important information and ignore distraction is critical for optimal memory performance, particularly when we experience a stressful or emotionally arousing event that consumes attentional resources. Evidence suggests that the locus coeruleus (LC), the part of our brain thought to instigate these selectivity processes under arousing conditions, degrades in aging and Alzheimer’s disease (AD). Yet little is known about the relationship between the LC and cognitive function in these populations. The goal of this research is thus to address a novel and critical research question: to determine the role of the LC in facilitating memory selectivity and how its role may be altered in aging and AD.

Details

Our goal is to determine the role of the locus coeruleus (LC)-norepinephrine (NE) system in facilitating memory selectivity and how the influence of this system may be altered in aging and Alzheimer’s disease (AD). When stressed or aroused by an alarming event, the ability to selectively focus on high-priority information and ignore distractions is critical for survival. There is evidence that the LC, a small brainstem nucleus, facilitates cognitive selectivity by releasing NE throughout the brain under arousal, which modulates attention and memory selectivity. The LC has also been identified as an important contributor to cognitive aging as reduced LC volume and cell density has been observed and linked to mild cognitive impairment and Alzheimer’s disease (AD). Moreover, recent autopsy evidence indicates that the LC is the first brain region to exhibit tau pathology that may even precede amyloid pathology, yet little work has focused on how the LC relates to cognitive function in aging and AD. Using functional magnetic resonance imaging (fMRI), the primary aim of our work is to determine age differences in how activation of the LC-NE system via emotional arousal influences the ability to selectively attend to and remember high-priority information and suppress competing distraction. Until recently, it has been difficult to study the LC with conventional neuroimaging given its small size. We will thus use neuromelanin-sensitive weighted MRI scans to visualize the LC and measure its signal intensity. Neuromelanin is a pigmented polymer resulting from oxidation of catecholamines, including NE in the LC, and so acts as a natural contrast agent that can localize the LC. Using these scans will thus enable us to determine how LC integrity corresponds to brain activity and behavior during a memory selectivity task completed in the MRI scanner. This project is unique as it will be one of the first to examine how LC structure and function relate to cognitive selectivity in healthy aging and AD. Given that the LC has been implicated in cognitive reserve and the development of AD-related pathology, it is critical to understand how age-related changes in this brain structure contribute to cognitive function. The importance of addressing such questions continues to rise as the aging population of America swells at a rapid pace and AD remains the nation’s sixth-leading cause of death.

About the Researcher

I completed my PhD in psychology at Ryerson University (Toronto, Canada) with Dr. Lixia Yang where I concentrated my research in cognitive aging. During my doctorate, I investigated how healthy aging influences metacognitive monitoring and control of emotional memory as well as the neural mechanisms underlying these processes using electroencephalography (EEG). After completing my PhD, I moved to Los Angeles to begin my postdoctoral fellowship in the Davis School of Gerontology at the University of Southern California. I joined the lab of Dr. Mara Mather so that I could study age-related changes in how the noradrenergic system influences memory selectivity under emotionally arousing conditions. To address our questions, we are using a combination of behavioral, psychophysiological, and neuroimaging techniques that enable us to study activity in LC-NE system and its effect on cognition in healthy aging and Alzheimer’s disease.

Personal Story

I've always been interested in understanding how we make sense of our environment. With a constant influx of sensory inputs, how does the brain know which information to remember and which to ignore? As an undergraduate at the University of Windsor (Ontario, Canada), such questions led me to gain research experience in a comparative cognition lab, where I studied sequential behavior in the rat. At the same time, I was volunteering in the caregiver-relief program at the Windsor-Essex Alzheimer Society, participating in recreational activities with individuals in varying stages of dementia. This allowed me to see first-hand how cognitive processes that we often take for granted, such as focusing on current tasks or thoughts, can be altered by diseases like Alzheimer’s and inevitable factors like aging. Most importantly, I saw the challenges that these changes had for the patients and their caregivers. These experiences motivated me to focus my PhD and postdoctoral research on understanding how fundamental cognitive functions that we use on a daily basis are affected by aging and AD. My ultimate goal is to identify ways that we can protect or preserve cognitive and brain function into the later stages of life. Given the role that the LC may play in the accumulation of AD-related pathology, I hope that our project will bring us closer to understanding how functioning of the LC-NE system relates to cognitive health in aging and AD. I am grateful to the BrightFocus Foundation donors for their generous support, which has enabled me to pursue these critical research questions.

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