Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)

Abstract

Background Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2–4 years after diagnosis. Methods Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. Results We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI − 1.2; − 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI − 52.9; − 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. Conclusions A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924.

Interventions promoting cognitive function in patients experiencing cancer related cognitive impairment: A systematic review

“…Four studies investigated exercise interventions including a group‐based community exercise program, 81 walking, 79 breathing with light exercise 82 and aerobic exercise with Nordic power walking 80 . A community‐based exercise program found no statistically significant improvements in subjectively measured cognitive function 81 .…”

“…found that a home‐based self‐implemented walking intervention over 12 weeks improved memory capacity ( p = 0.03) as measured by the Welschler Adult Intelligence Scale (WAIS). Koevoets et al 80 . conducted an RCT investigating the impact of aerobic exercise with Nordic power walking.…”

“…Koevoets et al. 80 conducted an RCT investigating the impact of aerobic exercise with Nordic power walking. Only borderline improvement in the cognitive functioning scale of the EORTC QLQ C‐30 was noted ( p ‐value not reported).…”

“…Some tools measured cognitive function across multiple domains (i.e., WAIS) and statistically significant results were reported in multiple domains accordingly. 76 Included exercise-based studies (n = 4) involved only patients with breast cancer, with some recruiting participants already reporting cognitive dysfunction post-treatment 80 and others including women prior to beginning chemotherapy. 79,82 Recent clinical trials also demonstrated improvements using melatonin to treat cancer-related fatigue.…”

Relationship Between Physical Exercise and Cognitive Impairment Among Older Adults with Type 2 Diabetes: Chain Mediating Roles of Sleep Quality and Depression

“…A randomized controlled study found a significant effect of reduced depression and improved sleep quality on the relationship between motor functions and COI in older adults. 13 It has also been found that regular PE improved sleep quality and alleviated depression, 14 which in turn have been indicated to mitigate the development of COI. 13 Studies have also shown that there is a marked negative relationship between sleep quality and depression 15 and that low levels of sleep quality can also contribute to psychological and psychiatric disorders.…”