Exercise May Ease ‘Chemo Brain’ and Fatigue, Study Finds

A simple home-based exercise plan helped patients stay active during chemotherapy, reducing mental fatigue and showing potential to ease “chemo brain,” especially in those on shorter treatment cycles.

Cancer-related cognitive impairment (CRCI) affects up to 75% of patients, often accompanied by mental fatigue, significantly reducing independence and quality of life. A study published in the Journal of the National Comprehensive Cancer Network found that the EXCAP exercise program may reduce overall mental fatigue and lessen self-reported cognitive impairment, particularly in patients receiving chemotherapy every two weeks.

‘Chemo Brain’ and Fatigue: Understanding the Impact

Cancer-related cognitive impairment (CRCI) can commence during cancer treatment or any time within the subsequent ten years. Symptoms include poor attention and verbal memory, reduced executive function, and slowed mental processing. These cognitive challenges can interfere with activities of daily living (ADL), such as managing medication, finances, shopping, traveling, housekeeping, and driving.

Chemotherapy can inhibit physiologic anti-inflammatory responses, leading to a pro-inflammatory state that disrupts normal immunologic function and potentially causes immunodeficiency.

How Exercise May Facilitate Regulate Inflammation

Exercise may help regulate the pro-inflammatory responses that predominate in patients undergoing chemotherapy. During exercise, pro-inflammatory cytokines like IFN-γ and IL-1β are initially released, followed by self-regulation through the release of anti-inflammatory signaling molecules, such as IL-10.

Exercise also stimulates the release of IL-6 from skeletal muscle cells. Although often considered a pro-inflammatory signal, exercise-associated IL-6 acts as a myokine – an anti-inflammatory signaling molecule from muscle cells.

Previous research by the study authors demonstrated that the Exercise for Cancer Patients (EXCAP) intervention was associated with higher immunocompetence, suggesting a better balance between inflammation and anti-inflammation.

The EXCAP Study: A Randomized Clinical Trial

Researchers conducted a multicenter, phase III randomized controlled trial (RCT) to examine the effectiveness of a tailored, progressive exercise strategy for home use in patients with CRCI and mental fatigue. They also assessed the associations between exercise, CRCI, and inflammation in cancer patients on chemotherapy.

EXCAP is a six-week home-based intervention incorporating walking and resistance band exercises, designed in collaboration with certified exercise professionals from the University of Rochester Medical Center. Participants received individualized exercise plans from trained staff at the start of chemotherapy.

The study included 687 patients randomized to receive EXCAP or usual care. Exercise intensity and adherence were assessed using a daily exercise diary, pedometer, and resistance exercise scale.

Researchers evaluated CRCI and mental fatigue before and after the intervention, and measured serum levels of five selected pro- and anti-inflammatory cytokines, the cytokine receptor sTNFR1, and overall inflammatory response patterns. Participants also recorded their thoughts about the exercise and the study.

Key Findings: Walking and Resistance Training Make a Difference

Dropout rates were similar in both groups. EXCAP participants averaged approximately 4,351 steps (about two miles) per day after six weeks, while the usual care group reduced daily steps by 53% (over one mile) from a pre-intervention average of 4,076 steps per day.

The EXCAP group walked nearly 2,000 more steps daily than the usual care group, who averaged less than 2,000 steps per day. The authors emphasize the importance of this finding, noting that walking less than 2,000 steps per day is significantly associated with higher all-cause mortality.

EXCAP participants also performed resistance-band exercises three times a week for about 25 minutes at moderate intensity. In contrast, the usual care group engaged in minimal exercise, with a maximum of three sessions over the six-week study period.

While all participants experienced cognitive decline and worsening mental fatigue during chemotherapy, the severity was significantly lower in the EXCAP group receiving chemotherapy every two weeks. No increase in mental fatigue was observed in this group, unlike the usual care group. These differences were evident in post-intervention tests.

No significant differences were observed between groups in patients receiving longer chemotherapy courses. The authors suggest this may be due to greater illness severity or other drug toxicities affecting response to EXCAP. Alternatively, they propose that these patients may require more intensive or prolonged exercise, or may have genetic predispositions affecting their cardiometabolic response to exercise.

Inflammation, CRCI, and Exercise: A Complex Relationship

The researchers found that greater exercise was associated with higher FACT-Cog scores (indicating less cognitive impairment), and a healthier inflammatory response pattern was associated with better cognitive function, although these relationships were associative.

The vast majority of EXCAP participants reported enjoying exercise more after the study and would recommend the program to other patients undergoing chemotherapy to reduce CRCI.

Study Limitations

This study has limitations, including the absence of a behavioral placebo and a lack of objective assessments of cancer-related cognitive impairment and mental fatigue. The exercise intervention may have been limited in scope, and the sample, primarily White females with breast cancer, limits the generalizability of the findings. Further research is needed to identify specific inflammatory signatures underlying CRCI and mental fatigue.

Practical Implications: Home-Based Exercise for Chemotherapy Patients

Individualized exercise programs can help patients maintain walking and resistance band exercise levels comparable to those before chemotherapy. This is associated with reduced mental fatigue and may lessen CRCI, particularly in patients receiving chemotherapy every two weeks. Maintaining daily step counts above thresholds associated with higher mortality is also beneficial.

This confirms the ability of exercise to mitigate CRCI under certain treatment conditions, and adds the observation that it can also help prevent worsening mental fatigue during chemotherapy. The intervention was successfully implemented by community-based oncology staff trained to administer EXCAP and monitor adherence.