# Aging trajectories and outcomes of older adults with acute myeloid leukemia

> **NIH NIH R37** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $489,655

## Abstract

PROJECT SUMMARY
In the US, over one-third of older adults ≥60 years with acute myeloid leukemia (AML) die without receiving any
chemotherapy, primarily due to concerns of cognitive decline and loss of functional independence if they chose
to undergo intensive chemotherapy. A combination of venetoclax and low-intensity chemotherapy offers an
effective new treatment for AML. However, several knowledge gaps exist about this new approach. Venetoclax
targets neuroprotective B-cell lymphoma 2 (Bcl-2) proteins, but the actual risk of cognitive decline and loss of
functional independence following its use, and the factors that increase such risks, are still unclear. Our
preliminary data demonstrated that many older adults with AML had stable or improved cognitive and physical
function, functional independence, and health-related quality of life (HRQOL) from the time of diagnosis to three
months following newer treatments. These novel findings highlight the success of newer treatments in improving
cognitive function, functional independence, and HRQOL. Despite this, frailty and multimorbidity were identified
as risk factors for functional decline. We also utilized the NCI-recommended neuroscience approach and
conducted electroencephalography (EEG)/event-related brain potential (ERP) studies. In our study, adults with
hematological cancers versus healthy adults demonstrated altered activity in the dorsal attention and central
executive brain networks prior to treatment. Confirmation of these findings will identify the risk of a decline in
attention and executive function, functional independence, and HRQOL, and will provide novel mechanistic
insights into the activity of brain networks in older adults with AML. In the proposed longitudinal cohort study, we
will enroll older adults with a new diagnosis of AML who will receive venetoclax-based treatments, and age-,
sex-, and education-matched non-cancer controls. We will compare the two groups on the following outcomes:
attention and executive function (Trail Making and other neuropsychological tests), functional independence,
HRQOL, and EEG/ERP measures (ERP studies during auditory-visual distraction tasks to measure brain activity)
at enrollment and over 12 months. The study aims are: Aim 1. Determine the longitudinal attention and executive
function of older adults with AML before and after venetoclax-based treatment, as compared to age-, sex-, and
education-matched non-cancer controls. Aim 2. Determine longitudinal changes in functional independence and
HRQOL in older adults with AML versus controls, and examine their associations with longitudinal changes in
attention and executive function. Aim 3. Measure longitudinal changes in the activity of brain networks of older
adults with AML before and after venetoclax-based treatment, as compared to controls. This is the first study to
apply rigorous methods to overcome key limitations of prior studies and to advance the current limited cognitive
aging resear...

## Key facts

- **NIH application ID:** 10886813
- **Project number:** 5R37CA276928-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Vijaya Raj Bhatt
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $489,655
- **Award type:** 5
- **Project period:** 2023-07-12 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886813

## Citation

> US National Institutes of Health, RePORTER application 10886813, Aging trajectories and outcomes of older adults with acute myeloid leukemia (5R37CA276928-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10886813. Licensed CC0.

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