# A Novel Computerized Cognitive Stress Test Designed for Clinical Trials in Early Alzheimer's: Relationship with Multimodal Imaging Biomarkers in Diverse Cultural Groups

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $726,721

## Abstract

Project Summary
 Emerging clinical trials focusing on preclinical Alzheimer's disease (AD) are expected to be most
effective in the earliest or even prodromal stages of illness, before significant multi-system degeneration has
occurred. To that end, it is critical to the success of emerging clinical trials to be able to identify and target
individuals that are truly at-risk for AD. Reliably identifying these at-risk individuals; however, is currently cost
prohibitive in large-scale trials given the reliance on AD biomarkers such as amyloid imaging to increase
confidence in the diagnostic determination. To facilitate the feasibility of preclinical AD trials, the field must
develop clinical outcome measures that are validated to identify early disease states with high levels of
sensitivity and specificity. This approach in turn, would be significantly cost effective and has the potential to
ultimately optimize clinical trial enrollment. Outcome measures must also be effective in measuring potential
changes in treatment response over time, be related to biomarkers of early AD pathology (e.g., amyloid load,
tau deposition, volumetric loss in AD prone regions on MRI), and be cross-culturally applicable given the
growing Hispanic population in the United States.
 Our laboratory has been at the forefront of developing assessment paradigms that are both sensitive
and specific to preclinical AD. One such novel memory paradigm, the LASSI-L taps the failure to recover from
proactive semantic interference (frPSI) and has been shown to be significantly more sensitive to early cognitive
deficits than learning inefficiency or simple rate of forgetting as is measured by the ADAS-Cog. The LASSI-L
has also outperformed other widely used measures in detecting preclinical AD. More specifically, frPSI has
been observed in otherwise cognitively normal elders with high amyloid load and decreased volumes in AD
prone regions among elders with amnestic MCI (aMCI) and PreMCI suggesting that this paradigm represents a
cognitive marker of very early AD. We have now significantly expanded our earlier work to develop a
computerized Cognitive Stress Test (CST), designed to more strongly elicit cognitive markers of preclinical AD.
In the current study, we intend to validate this novel and more powerful CST for use in preclinical AD trials by
examining the performance of 240 Hispanic and non-Hispanic individuals with early stage MCI (eMCI) as
compared to elders with no cognitive impairment and in relation to traditional measures employed in AD clinical
trials such as the ADAS-Cog, longitudinally. We will also examine the relatedness of the CST to biological
markers of AD: PET amyloid load, MRI measures of volume and cortical thickness, DTI and tau burden.
 The proposed investigation will provide an unparalleled opportunity to validate and establish a
novel and promising cognitive outcome measure specifically designed to detect preclinical AD, for use in
preclinical AD trials as b...

## Key facts

- **NIH application ID:** 10064122
- **Project number:** 5R01AG061106-03
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** DAVID LOEWENSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $726,721
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064122

## Citation

> US National Institutes of Health, RePORTER application 10064122, A Novel Computerized Cognitive Stress Test Designed for Clinical Trials in Early Alzheimer's: Relationship with Multimodal Imaging Biomarkers in Diverse Cultural Groups (5R01AG061106-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064122. Licensed CC0.

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