A simple home-based exercise program may help counter “chemo brain,” but adding ibuprofen does not boost the benefit and may even complicate memory outcomes, highlighting the need for larger trials.
Study: Phase 2 trial of exercise and low-dose ibuprofen for cancer-related cognitive impairment in patients receivingchemotherapy. Image credit: Pixel-Shot/Shutterstock.com
Preliminary findings suggest that exercise and low-dose ibuprofen, individually but not in combination, could improve some aspects of cancer-related cognitive impairment (CRCI) in patients undergoing chemotherapy. The paper was published in the journal Cancer.
Chemotherapy-related cognitive decline linked to inflammatory processes
CRCI affects up to 80 % of cancer patients on chemotherapy, called “chemo brain”, and is thought to partly arise from inflammation. Exercise has proved to be an aid in mitigating cancer-related fatigue, mental distress, and reduced function.
Exercise for Cancer Patients©® (EXCAP) is a home-based 6-week program for cancer patients that includes exercise at low to moderate-intensity, progressive walking and resistance exercise as prescribed. Its anti-inflammatory benefits in chemotherapy patients have been described in earlier work by the authors of the current study.
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), and at low dosage it may have a potential but not yet clinically established protective effect on CRCI.
The aim of the current phase 2 trial was to identify the preliminary efficacy of these agents in preventing or reducing the severity of CRCI in non-exercising patients undergoing chemotherapy. Since their actions might occur through distinct pathways, additive or synergistic effects are possible, although no significant interaction between the two interventions was observed in this study.
Phase 2 trial tests exercise and ibuprofen combinations
The study included 86 participants (with a mean age of 54 years), almost all non-Hispanic non-Latino White females. Most were married, employed, and had breast cancer.
Participants were randomized into the following groups: EXCAP–ibuprofen, EXCAP–placebo, ibuprofen only, and placebo only.
Ibuprofen and placebo were administered at 200 mg twice a day, on a double-blinded basis, for six weeks. Cognitive testing was performed at baseline, on memory, attention, and executive function. Immune markers, fitness assessments, and measures of anxiety and depression were also obtained from all participants.
EXCAP promotes activity
In the EXCAP groups, daily steps increased over time, from sedentary to low-active levels. EXCAP groups walked an average of 5650 steps per day, versus 3982 steps per day in non-EXCAP groups.
More people in the EXCAP groups also walked 5000 or more steps a day over time (from 30 % at baseline to 51 % post-intervention).
Selective improvement with exercise and ibuprofen
Improvements in attention
Compared to placebo, the EXCAP-placebo group showed the strongest improvements in attention, followed by the ibuprofen-only group. These effects were primarily observed in attention-related tests such as the Trail Making Test.
Notably, participants in the placebo group experienced worsening attention over time, whereas those in the EXCAP-placebo group improved. This contrast highlights the potential for exercise to counter cognitive decline during chemotherapy.
Faster information processing
Participants in the EXCAP-placebo group also demonstrated improved performance on Rapid Visual Processing tasks, reflected by reduced response latency. A similar, but weaker, trend was observed in the ibuprofen group, suggesting a possible but less consistent effect on processing speed.
Patient-reported cognitive changes
Both EXCAP groups reported better scores on the FACT-Cog “comments from others” subscale compared to placebo. This indicates that participants perceived improvements in how others viewed their cognitive functioning.
The EXCAP-ibuprofen group showed the largest improvement, while the EXCAP-placebo group showed a positive trend. However, these effects were limited to this specific subscale and did not extend to all measures of perceived cognition.
Mixed effects on memory
The effects on memory were inconsistent. Participants receiving ibuprofen showed less improvement on delayed verbal memory (Hopkins Verbal Learning Test-revised) compared to those not receiving ibuprofen, suggesting a possible negative or variable impact on this domain.
Although some within-group improvements in memory were observed across several groups, these were not significantly different between intervention arms.
No consistent benefit across all cognitive domains
Despite improvements in attention and processing speed, many cognitive outcomes, including visual memory and executive function, did not differ significantly between groups. Some observed improvements over time may reflect general study participation or repeated testing rather than true intervention effects.
No added benefit from combining interventions
Although exercise and ibuprofen each showed some independent effects, combining them did not produce additional cognitive benefits.
Strengths and limitations
The study followed a randomized controlled trial (RCT) design performed during rather than following chemotherapy. Different types and stages of cancer were included. Comprehensive cognitive testing and high adherence rates improve the value of the findings.
Some limitations exist, however, primarily the small sample size, lack of statistically significant interaction between EXCAP and ibuprofen, and the lack of diversity in predominant cancer type and ethnic composition.
The results suggest that exercise could effectively alleviate specific aspects of cognitive impairment during chemotherapy. Low-dose ibuprofen also produced improvement in some measures, albeit weaker, and with mixed results in other areas, including potential negative effects on verbal memory.
The findings need to be confirmed by phase 3 trials over a longer duration to assess long-term efficacy, as this study only evaluated short-term outcomes over six weeks, and did not assess durability after the intervention ended.
Download your PDF copy by clicking here.
Competition between brain circuits is key to intelligent behavior