Dataset Information

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; VO_2peak), 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 VO_2peak 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 .

SUBMITTER: Koevoets EW

PROVIDER: S-EPMC9135390 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Koevoets E W EW Schagen S B SB de Ruiter M B MB Geerlings M I MI Witlox L L van der Wall E E Stuiver M M MM Sonke G S GS Velthuis M J MJ Jobsen J J JJ Menke-Pluijmers M B E MBE Göker E E van der Pol C C CC Bos M E M M MEMM Tick L W LW van Holsteijn N A NA van der Palen J J May A M AM Monninkhof E M EM

Breast cancer research : BCR 20220526 1

<h4>Background</h4>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.<h4>Methods</h4>Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological t ...[more]

PMID: 35619188

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Project description:BackgroundPhysical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory.MethodsChemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients.ResultsMultiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015).ConclusionsNo exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding.

Project description:PurposeMinocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy.MethodsThis is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.ResultsFifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).ConclusionDespite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.

Project description:BackgroundPotential moderators such as exercise intensity or apolipoprotein-E4 (ApoE4) carriership may determine the magnitude of exercise effects on physical and cognitive functions in patients with dementia (PwD). We determined the effects of a 24-week aerobic and strength training program with a low- and high-intensity phase on physical and cognitive function.MethodsIn an assessor-blinded randomized trial, 91 PwD (all-cause dementia, recruited from daycare and residential care facilities, age 82.3 ± 7.0 years, 59 women, Mini-Mental State Examination 20.2 ± 4.4) were allocated to the exercise or control group. In the exercise group, PwD participated in a walking and lower limb strength training program with 12 weeks low- and 12 weeks high-intensity training offered three times/week. Attention-matched control participants performed flexibility exercises and recreational activities. We assessed adherence, compliance, and exercise intensity for each session. We assessed physical (endurance, gait speed, mobility, balance, leg strength) and cognitive (verbal memory, visual memory, executive function, inhibitory control, psychomotor speed) functions with performance-based tests at baseline and after 6, 12, 18, 24, and 36 weeks (follow-up). ApoE4 carriership was determined post-intervention.ResultsSixty-nine PwD were analyzed. Their mean attendance was ~ 60% during the study period. There were no significant effects of the exercise vs. control intervention on endurance, mobility, balance, and leg strength in favor of the exercise group (Cohen's d = 0.13-0.18). Gait speed significantly improved with ~ 0.05 m/s after the high-intensity phase for exercise participants (Cohen's d = 0.41) but declined at follow-up. There were no significant effects of the exercise vs. control intervention on any of the cognitive measures (Cohen's d ~ - 0.04). ApoE4 carriership did not significantly moderate exercise effects on physical or cognitive function.ConclusionsExercise was superior to control activities for gait speed in our sample of PwD. However, the training effect provided no protection for mobility loss after detraining (follow-up). There were no beneficial effects of the exercise vs. control group on cognitive function. Exercise intensity moderated the effects of exercise on gait speed. ApoE4 carriership moderated the effect of exercise on global cognition only (trend level).Trial registrationNetherlands Trial Register, NTR5035. Registered on 2 March 2015.

Project description:PurposeCompare the effects of low-intensity and moderate-intensity exercise on physical functioning in breast cancer survivors.MethodsWomen aged 50 + years and post-primary treatment for stage 0 to III breast cancer were randomly assigned to a 6-month low-intensity (LIG) or moderate-intensity (MIG) exercise group. Participants were instructed to walk (low- or moderate-intensity) for 30 min five days a week, followed by flexibility exercises, and do strengthening and balance exercises twice weekly. Exercise adherence was facilitated with seven individual counseling sessions tapered over six months and a Theory of Planned Behavior-based booklet. Assessments occurred at baseline, 6 months (post-intervention), and 12 months. Primary measures were PROMIS Physical Functioning, PROMIS Global Health, and six-minute walk test (6MWT).ResultsOf 101 women randomized, 65 (64.4%) completed the study. No statistically significant between-group differences occurred at post-intervention or 12 months. Compared to baseline, within-group improvements in PROMIS physical functioning occurred (LIG increased from 45.87 ± 7.58 to 48.37 ± 7.13 post-intervention (p = 0.01); MIG increased from 45.26 ± 7.27 to 49.53 ± 8.80 post-intervention (p = 0.002) and 48.91 ± 9.29 at 12 months (p = 0.02)). Similarly, Global Health physical health improved (LIG increased from 46.04 ± 5.00 to 49.19 ± 5.76 post-intervention (p = 0.001); MIG increased from 45.06 ± 6.59 to 48.20 ± 7.33 post-intervention (p = 0.005) and 48.49 ± 7.89 at 12 months (p = 0.007)). 6MWT improved between post-intervention and 12 months for the LIG (469.99 ± 64.69 m to 492.19 ± 68.64 m, p = 0.008) and between baseline and post-intervention for the MIG (471.01 ± 62.69 m to 495.88 ± 66.64 m, p = 0.006).ConclusionBoth low and moderate-intensity exercise led to significant improvement in physical functioning. When feasible and acceptable, prescribing low-intensity exercise can yield important benefits.Trial registration numberClinicalTrials.gov identifier: NCT02982564.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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