# Working Memory in Preclinical Alzheimer's Disease: a Neuropsychological and Neuroimaging Investigation

> **NIH NIH F31** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $36,472

## Abstract

PROJECT SUMMARY / ABSTRACT
Alzheimer's disease (AD) is a debilitating neurocognitive disorder that is characterized by an insidious onset
and progressive course of memory decline and deficits in other cognitive domains, such as working memory.
Recently, AD research has focused on the preclinical detection and treatment of the disease, as earlier
detection and intervention may allow us to halt or slow AD pathogenesis. Previous research has identified
working memory difficulties in early symptomatic AD, suggesting that changes in this cognitive domain may
precede or co-occur with episodic memory impairment. Using resting and task-based activation and
connectivity on functional magnetic resonance imaging (fMRI) is a novel way to characterize the brain markers
and mechanisms that underpin working memory performance in preclinical AD. Neuropsychological measures
of working memory may reveal only subtle behavioral differences between individuals with preclinical AD and
healthy adults, but task and resting fMRI activation and connectivity in working-memory related networks may
be able to identify aberrant patterns that distinguish individuals at risk for AD. It is possible that network
disruption in working memory-related areas may also moderate the observed relation between AD brain
pathology (cortical amyloid-beta and medial temporal lobe tau) and episodic memory performance in the
preclinical stage of AD. This project will investigate (1) working memory-related task fMRI activation and
connectivity in preclinical ADAD; (2) the relation between working memory, episodic memory, and AD brain
pathology in preclinical ADAD and sporadic AD; and (3) resting-state brain network integrity in working
memory-related networks and its relations to AD brain pathology in preclinical sporadic AD and preclinical
autosomal dominant Alzheimer's disease (ADAD). Aim 1 will draw on young, cognitively unimpaired mutation
carriers and non-carrier family members from the Colombian ADAD kindred; carriers of this mutation
(presenilin1 E280A) are virtually guaranteed to develop dementia due to AD by their late 40s. Aims 2 and 3 will
similarly recruit Colombian kindred carriers and non-carriers, as well as cognitively normal older adults at risk
for sporadic AD based on elevated molecular markers of AD pathology see on positron emission tomography
(PET) in the brain. Through this project the applicant will (1) gain expertise in imaging and neuropsychological
methods related to investigating the neural correlates of working memory in preclinical ADAD and preclinical
sporadic AD, (2) receive training and mentorship on experimental design pertaining to cognitive and imaging
research on neurodegenerative diseases, and (3) establish professional relationships with experienced
researchers and collaborators who will equip him with the skills to transition to career independence.

## Key facts

- **NIH application ID:** 10246432
- **Project number:** 5F31AG062158-03
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Joshua Thomas Fuller
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,472
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246432

## Citation

> US National Institutes of Health, RePORTER application 10246432, Working Memory in Preclinical Alzheimer's Disease: a Neuropsychological and Neuroimaging Investigation (5F31AG062158-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246432. Licensed CC0.

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