# How LC Integrity in Older Adults Mediates Perceptual and Memory Processes

> **NIH NIH RF1** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2022 · $388,699

## Abstract

The goal of this supplement is to understand relationships between HIV infection and neurocognitive decline in
people aging with HIV. This is in the context of the larger project to understand how individual differences in the
structure and function of Locus Coeruleus (LC) moderate perception and memory in an older adult population.
There is substantial evidence that the LC circuit plays a central role in cognitive processes and neuronal loss in
LC is known to occur in neurodegenerative disorders such as ADRD and PD. Integrity of LC neurons is
hypothesized to mediate the preservation of cognitive abilities during normal aging as well. To date, however,
there exists a dearth of research that either characterizes differential effects of LC integrity or details relationships
between LC integrity and cognitive function in older adult humans. There is even less information on how the LC
ages in people living with HIV (PLWHIV). More generally, the link between LC activity and cognitive processes
has not been well characterized in humans. Historical reasons for this is that the LC has been difficult to image
due to its small size and thus most human research makes inferences about LC function by using pupil dilation
as a surrogate measure. To overcome existing limitations in the field, we propose a series of detailed
psychophysical and MRI-based studies in older adults aimed to characterize how LC structure and function
moderates behavior and in turn how this is mediated by activity in intermediate brain regions known to be
involved in perceptual and memory processes. We further propose computational approaches to characterize
individual differences in how LC circuit integrity relates to different patterns of cognitive performance across
tasks, and advanced neuroimaging methods to localize and image the LC, which have been pioneered by our
group. Using MRI-based methods, we will examine LC integrity using high-resolution neuromelanin-sensitive
structural imaging, tractography and functional connectivity. This approach will allow us to identify candidate
biomarkers of LC circuit integrity. Overall this study will provide an important and much needed understanding
of how LC integrity underlies cognitive declines in older adults, including PLWHIV. By combining advanced
neuroimaging, well-controlled behavioral assessment, and computational analysis, we expect to uncover
previously inaccessible in vivo mechanisms of LC modulation and generate a unique dataset to address
fundamental mechanistic questions of how the LC integrity moderates cognition, how this varies across older
adults with and without HIV and the extent to which relationships between LC and cognition are generalized or
individualized to particular domains. The resulting understanding of LC circuit can help explain how dysfunctional
modulatory circuits may generate cognitive declines or be implicated in normal aging, those aging with HIV and
Alzheimer’s and Alzheimer’s related disorders. This, ...

## Key facts

- **NIH application ID:** 10613285
- **Project number:** 3RF1AG072607-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** XIAOPING P HU
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $388,699
- **Award type:** 3
- **Project period:** 2021-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10613285

## Citation

> US National Institutes of Health, RePORTER application 10613285, How LC Integrity in Older Adults Mediates Perceptual and Memory Processes (3RF1AG072607-01S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10613285. Licensed CC0.

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