Summary: As many as 80% of people receiving chemotherapy report cancer-related cognitive impairment — a constellation of memory lapses, trouble concentrating, and difficulty multitasking often called “chemo brain.” A new Phase II randomized trial tested two low-risk strategies — a home-based exercise program and low-dose ibuprofen — and found that both can reduce some cognitive declines, with exercise showing the most consistent benefit.
In this trial, a structured, progressive walking-and-resistance program (EXCAP) delivered at home and low-dose ibuprofen were each associated with improvements on selected cognitive measures after six weeks. Exercise produced the clearest gains in attention and processing speed, while ibuprofen showed mixed effects that warrant additional study.
Key Findings
- Exercise improved attention and processing: Participants in the EXCAP + Placebo group completed attention-based tests faster and more accurately than those who received placebo alone.
- Ibuprofen showed selective benefits and a surprising drawback: Low-dose ibuprofen improved some cognitive outcomes compared with placebo, but it was associated with less improvement on a measure of short-term verbal memory, an unexpected result that needs further evaluation.
- Real-world change noticed by others: Both exercise groups (EXCAP with and without ibuprofen) reported that friends, family, and coworkers commented less often about cognitive problems, suggesting benefits were visible in daily life.
- Exercise was the more robust intervention: Investigators observed stronger, more consistent effects from the exercise program across multiple measures, highlighting its broader value during chemotherapy.
Source: Wiley
Background: Cancer-related cognitive impairment affects a large proportion of patients undergoing chemotherapy, most commonly causing mild-to-moderate problems with attention, memory, and multitasking. Although inflammation and other treatment-related processes are believed to play a role, effective, evidence-based interventions during chemotherapy have been limited.
To address this gap, researchers conducted a Phase II randomized, controlled trial to evaluate whether EXCAP — a home-based, low-to-moderate intensity, progressive walking and resistance exercise prescription — and low-dose ibuprofen could each protect cognition in patients receiving chemotherapy who already reported cognitive complaints.
The trial enrolled 86 participants (mean age 53.6; 88.37% female) who were randomized for six weeks into four arms: EXCAP + low-dose ibuprofen, EXCAP + placebo, low-dose ibuprofen only, and placebo only. Cognitive performance and patient-reported outcomes were measured at baseline and after the intervention, alongside relevant biological assessments.
Study Results
The EXCAP + Placebo arm showed the clearest benefit on timed attention tasks: participants completed the Trail Making Test significantly faster than those in the placebo group (a mean difference of approximately 21.6 seconds, indicating better performance). The ibuprofen-only group also improved versus placebo on this test, but to a lesser degree.
On a computerized rapid visual processing task, EXCAP participants again improved markedly compared with placebo, and there was a trend toward improvement for those taking ibuprofen after adjustment for baseline reading score. Both EXCAP arms also reported fewer “comments from others” about cognitive problems on the FACT-Cog questionnaire, indicating perceived improvements by social contacts.
Notably, the ibuprofen-only group performed worse on delayed verbal recall (Hopkins Verbal Learning Test-Revised delayed) than participants not receiving ibuprofen, a finding the authors flagged for further study because it contrasts with other improvements tied to ibuprofen.
Conclusions
Overall, the Phase II trial showed that a structured home exercise program can meaningfully improve certain cognitive domains for patients receiving chemotherapy. Low-dose ibuprofen also produced cognitive benefits on some measures but lacked consistency across outcomes and raised a concern about delayed verbal memory. These findings support the need for larger Phase III trials to confirm benefits, optimize duration and dosing, and clarify potential trade-offs.
Lead author Michelle C. Janelsins, PhD, MPH, emphasized the notable and consistent effects of exercise, adding that future research should explore different exercise durations and ibuprofen doses. She also recommended that patients consult their oncology team before starting any new medication or exercise program to ensure safety and avoid contraindications.
Key Questions Answered:
A: In this trial, a low-to-moderate walking and resistance program (EXCAP) was both safe and beneficial. Because chemotherapy affects people differently, patients should get approval from their oncologist before beginning a new exercise routine.
A: Low-dose ibuprofen showed some cognitive benefits in this study, but effects were inconsistent and one test showed less improvement in verbal memory among ibuprofen users. Exercise produced more reliable benefits and remains a preferred nonpharmacologic option based on these results.
A: Chemotherapy can trigger systemic inflammation and other physiological changes that may cross the blood-brain barrier or otherwise disrupt neural circuits involved in attention, executive function, and memory.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed for accuracy.
- Staff added context to clarify clinical implications and next steps for research.
About this neurology research news
Author: Sara Henning-Stout
Source: Wiley
Contact: Sara Henning-Stout – Wiley
Image: The image is credited to Neuroscience News
Original Research: Open access. “Phase II Trial of Exercise and Low-Dose Ibuprofen for Cancer-Related Cognitive Impairment in Patients Receiving Chemotherapy” by Michelle C. Janelsins et al., published in Cancer. DOI: 10.1002/cncr.70323
Abstract
Phase II Trial of Exercise and Low-Dose Ibuprofen for Cancer-Related Cognitive Impairment in Patients Receiving Chemotherapy
Background
Interventions to prevent or reduce cancer-related cognitive impairment during treatment are limited and understudied. This trial explored two feasible approaches — structured home-based exercise and low-dose ibuprofen — to determine whether either could protect cognition during chemotherapy.
Methods
Eighty-six patients receiving chemotherapy who reported cognitive difficulties were randomized in a 2 × 2 factorial Phase II design to one of four six-week arms: EXCAP–ibuprofen, EXCAP–placebo, ibuprofen only, or placebo only. EXCAP is a progressive, home-based walking and resistance program at low-to-moderate intensity. Cognitive testing and biological measures were collected before and after the intervention period.
Results
Between-group comparisons demonstrated that EXCAP–placebo participants had significantly faster performance on the Trail Making Test compared to placebo (mean difference ≈ −21.57 seconds, p < .001). The ibuprofen-only group also improved relative to placebo on this task but to a lesser extent. Both EXCAP groups reported fewer comments from others about cognitive problems. Ibuprofen was associated with less improvement on a delayed verbal memory measure, a result that requires further investigation.
Conclusions
A six-week home-based exercise program improved selected cognitive outcomes in patients receiving chemotherapy. Low-dose ibuprofen produced some cognitive benefits but with inconsistent effects across measures and a potential negative signal for delayed verbal memory. Larger Phase III trials are necessary to confirm these findings and to refine intervention protocols for clinical use.