# Repetition Priming Deficits and Locus Coeruleus Dysfunction in Alzheimer's Disease

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $51,752

## Abstract

Project Summary/Abstract
 In addition to the characteristic deficits in explicit memory for facts or past events, patients with
Alzheimer's disease also demonstrate an underappreciated impairment in repetition priming, an essential form
of implicit memory. Priming refers to a performance enhancement that occurs simply due to repeated exposure
to a stimulus, and occurs without conscious recollection of the stimulus. Priming is preserved in patients with
explicit memory deficits due to circumscribed damage to the medial temporal lobe (MTL) explicit memory
system (e.g. patient “H.M.”), but is impaired in a modality-specific manner with lesions of cortex supporting
processing of that modality. While AD pathology spreads widely throughout the cortex in the later stages of
disease progression, priming impairments appear in patients with Mild Cognitive Impairment (a precursor to
AD) and even in the preclinical stages of disease - long before pathology has spread to affect other cortical
functions. Alternatively, recent work suggests that before affecting the cortex, AD pathology begins in
brainstem nuclei such as the locus coeruleus (LC) – the sole source of norepinephrine (NE) for the majority of
the neocortex – regulating arousal and attention, and providing a steady-state level of “cortical tonus.” It has
been proposed that early subcortical damage to this LC-NE system in AD compromises this tonic cortical
activation to a degree that is unable to support priming in the initial stages of disease, but until recently probing
the integrity of the NE system in vivo was technically challenging.
 The recent development of Fast Spin Echo (FSE) T1-weighted MR imaging techniques to utilize the
natural contrast properties of neuromelanin, a product of NE metabolism, has allowed the reliable identification
of the LC in vivo. The neuromelanin contrast intensity of the structure on FSE MRI has been pathologically
validated as a measure of LC cell loss, and has been found to relate to cognitive function in AD. Similarly,
pupillary response under cognitive load and measurement of salivary alpha-amylase (SAA) have recently been
used as proxies of NE system function and integrity. I propose to utilize these novel techniques to test the
hypothesis that the priming deficit in AD stems from early LC dysfunction by administering a perceptual open-
closed figure priming task along with a conceptual word-stem completion priming task to participants on the
aging-MCI-AD spectrum who are participating in a multi-modal imaging and pupillometry studies of the LC.
Using recent advances in techniques for the acquisition and analysis of both diffusion-weighted and resting-
state functional MRI, I will further test whether the structural and functional connectivity of the LC to modality-
specific cortical regions implicated in conceptual and perceptual repetition priming are separately related to our
conceptual and perceptual tasks. This work will not only expand our understanding o...

## Key facts

- **NIH application ID:** 10480896
- **Project number:** 5F30AG063440-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Denis Smirnov
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2019-09-12 → 2023-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480896

## Citation

> US National Institutes of Health, RePORTER application 10480896, Repetition Priming Deficits and Locus Coeruleus Dysfunction in Alzheimer's Disease (5F30AG063440-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10480896. Licensed CC0.

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