# Digital Assessment of Long-term Forgetting in Autosomal-Dominant Alzheimer's Disease

> **NIH NIH R61** · WASHINGTON UNIVERSITY · 2024 · $447,833

## Abstract

PROJECT SUMMARY
The essence of the Alzheimer’s disease (AD) phenotype is a decline in memory. Well before the onset of
obvious dementia, there are changes in memory that patients and family members notice which diminish
quality of life for those impacted. Therapeutic interventions that target the presymptomatic and early
symptomatic stages of AD often choose a cognitive endpoint to demonstrate efficacy, but conventional
memory assessments often fail to capture these subtle changes that occur early in the disease. One reason is
that conventional memory assessments do not reflect how memory is relied upon in the everyday lives of
participants. For example, it is very distressing for patients to experience memory lapses like forgetting first
names, losing personal items, or having difficulty remembering the plot of a book or film. Conventional memory
testing assesses recall at short periods, typically 30-minutes or less after learning the information, whereas in
the everyday lives of patients, critical information must be recalled over much longer periods like hours, days,
or even weeks to maintain quality of life. Several clinical studies have demonstrated that extending recall of
newly learned information past the usual 30-minute or less delay period to much longer intervals dramatically
increases the rate of decay, a concept known as accelerated long-term forgetting (ALF). We have shown that
participants who carry a mutation for autosomal dominant Alzheimer’s disease (ADAD) but who are
presymptomatic, perform similarly to non-carriers on conventional memory testing. Critically, when we tested
mutation carriers on their long-term recall at 7 days, they had lost much more information than non-carriers,
suggesting that extending the recall period may reveal important differences in memory consolidation that
manifest well before the onset of noticeable dementia symptoms.
 An obvious challenge for measuring ALF in clinical populations is burden. Conventional testing would
require multiple visits from study participants and require multiple interactions with study personnel, which is
practically and financially unfeasible. The increasing ubiquity of smartphones provides an opportunity to assess
cognition in populations at risk for AD, while allowing for longer-term follow-up without excessive burden or
financial impact. In this study, we will develop novel ALF measures for smartphone-based administration and
validate their effectiveness in presymptomatic autosomal dominant AD. Our development process will include
user experience studies and clinical trial readiness audits, and the resulting application source code will be
made freely available. The ultimate goal is to develop a highly sensitive, accessible, and clinically meaningful
cognitive endpoint for use in international AD clinical trials, including adding ALF measures to the Dominantly
Inherited Alzheimer Network-Trials Unit (DIAN-TU).

## Key facts

- **NIH application ID:** 10914241
- **Project number:** 5R61AG083581-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jason J Hassenstab
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $447,833
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914241

## Citation

> US National Institutes of Health, RePORTER application 10914241, Digital Assessment of Long-term Forgetting in Autosomal-Dominant Alzheimer's Disease (5R61AG083581-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10914241. Licensed CC0.

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