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

Author

Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.

Published
2022
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3. Effect of physical exercise on brain perfusion in chemotherapy-treated breast cancer patients: a randomized controlled trial (PAM study)

Author

Koevoets, E. W., (0000-0002-3201-6002) Petr, J., Monninkhof, E. M., Geerlings, M. I., Witlox, L., Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Palen, J., Jmm Mutsaerts, H., Ruiter, M. B., May, A. M., Schagen, S. B., Koevoets, E. W., (0000-0002-3201-6002) Petr, J., Monninkhof, E. M., Geerlings, M. I., Witlox, L., Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Palen, J., Jmm Mutsaerts, H., Ruiter, M. B., May, A. M., and Schagen, S. B.

Abstract

BACKGROUND Breast cancer patients may experience cognitive difficulties after chemotherapy. PURPOSE To investigate whether an exercise intervention can affect cerebral blood flow (CBF) in breast cancer patients and if CBF changes relate to memory function. STUDY TYPE Prospective. POPULATION Chemotherapy-treated breast cancer patients with cognitive problems, and with relatively low physical activity levels were randomized to an exercise intervention (n=91) or control group (n=90). FIELDSTRENGTH/SEQUENCE A 3-T arterial spin labeling CBF scan was performed. ASSESSMENT The 6-month intervention consisted of (supervised) aerobic and strength training, 4x1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after six months included the arterial spin labeling CBF scan, from which we calculated gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Furthermore, we measured physical fitness and memory functioning. STATISTICAL TESTS Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS We observed significant improvement in physical fitness (VO2peak) in the intervention group (n=53) compared to controls (n=51, B1.47, 95%CI:0.44; 2.50), nevertheless no intervention effects on CBF were found (e.g. whole brain: B0.98, 95%CI:-2.38; 4.34). Highly fatigued patients showed larger, but not significant, treatment effects. Additionally, change in physical fitness, from baseline to post-intervention, was positively associated with changes in CBF (e.g., whole brain: B0.75, 95%CI:0.07; 1.43). However, we observed no relation between CBF changes and change in memory performance. DATA CONCLUSION The exercise intervention did not affect CBF of cognitively affected breast cancer patients. However, a change in physical fitness was related to a change in CBF, but a change in CBF was not associated with memory functioning.

Published
2024

5. Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients:A randomized controlled trial (PAM study)

Author

Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E.M.M., Göker, E., Menke-Pluijmers, M. B.E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W.A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., Schagen, S. B., Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E.M.M., Göker, E., Menke-Pluijmers, M. B.E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W.A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., and Schagen, S. B.

Abstract

Background: Physical 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. Methods: Chemotherapy-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. Results: Multiple 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 =

Published
2023

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

Author

Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B.E., Göker, E., van der Pol, C. C., Bos, M. E.M.M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., Monninkhof, E. M., Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B.E., Göker, E., van der Pol, C. C., Bos, M. E.M.M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.

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

Published
2022

9. Additional file 1 of Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)

Author

Koevoets, E. W., Schagen, S. B., de Ruiter, M. B., Geerlings, M. I., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., Menke-Pluijmers, M. B. E., Göker, E., van der Pol, C. C., Bos, M. E. M. M., Tick, L. W., van Holsteijn, N. A., van der Palen, J., May, A. M., and Monninkhof, E. M.

Abstract

Additional file 1. Table S1. Intervention effects on cognitive functioning. Table S2. Intervention effects on cognitive functioning, per protocol. Table S3. Intervention effects, separately for patients with and without endocrine therapy. Table S4. Intervention effects, separately for patients of different age categories (30-44, 45-59, 60-75 years). Table S5. Intervention effects, separately for patients of with pre- and peri- menopausal status and patients with postmenopausal status. Table S6. Intervention effects on cognitive functioning, stratified for low versus high levels of fatigue measured with the EORTC QLQ C-30 fatigue scale. Table S7. Intervention effects on patient-reported outcomes.

Published
2022
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10. Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study)

Author

Koevoets, E. W., Geerlings, M. I., Monninkhof, E. M., Mandl, R., Witlox, L., van der Wall, E., Stuiver, M. M., Sonke, G. S., Velthuis, M. J., Jobsen, J. J., van der Palen, J., Bos, M. E. M. M., Göker, E., Menke-Pluijmers, M. B. E., Sommeijer, D. W., May, A. M., Haringhuizen, Annebeth W., van der Steeg, Wim A., Terheggen, Frederiek, Blanken-Peeters, Charlotte, Fliervoet, Harold, Schlooz-Vries, Margrethe S., Frakking, Tanja G., van Tilburg, Marc W. A., Oldenhuis, Corina, Sier, Maartje F., van der Pol, Carmen C., Tick, Lidwine W., van Holsteijn, Nel A., de Ruiter, M. B., Schagen, S. B., Psychology Other Research (FMG), Medical Oncology, General practice, Master Evidence Based Practice, CCA - Cancer Treatment and Quality of Life, APH - Quality of Care, APH - Health Behaviors & Chronic Diseases, Oncology, Radiology and Nuclear Medicine, and Rehabilitation medicine

Subjects
Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], All institutes and research themes of the Radboud University Medical Center, Breast cancer, SDG 3 - Good Health and Well-being, Neurology, Cognitive Neuroscience, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Grey matter volume, Exercise, Hippocampus, Fatigue, Cortical thickness
Abstract

Contains fulltext : 291410.pdf (Publisher’s version ) (Open Access) BACKGROUND: Physical 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. METHODS: Chemotherapy-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. RESULTS: Multiple 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 mm(3), 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 mm(3), 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). CONCLUSIONS: No 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.

Published
2023

18. Inter-observer variation of hippocampus delineation in hippocampal avoidance prophylactic cranial irradiation

Author

Bartel, F., primary, van Herk, M., additional, Vrenken, H., additional, Vandaele, F., additional, Sunaert, S., additional, de Jaeger, K., additional, Dollekamp, N. J., additional, Carbaat, C., additional, Lamers, E., additional, Dieleman, E. M. T., additional, Lievens, Y., additional, de Ruysscher, D., additional, Schagen, S. B., additional, de Ruiter, M. B., additional, de Munck, J. C., additional, and Belderbos, J., additional

Published
2018
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22. Self‐reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side‐study

Author

Schilder, C. M. T., primary, Seynaeve, C., additional, Linn, S. C., additional, Boogerd, W., additional, Beex, L. V. A. M., additional, Gundy, C. M., additional, Nortier, J. W. R., additional, van de Velde, C. J. H., additional, van Dam, F. S. A. M., additional, and Schagen, S. B., additional

Published
2011
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26. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy.

Author

van Dam FSA, Schagen SB, Muller MJ, Boogerd W, Wall E, Fortuyn MED, Rodenhuis S, van Dam, F S, Schagen, S B, Muller, M J, Boogerd, W, vd Wall, E, Droogleever Fortuyn, M E, and Rodenhuis, S

Abstract

Background: Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers, the long-term toxic effects of such therapy are a concern. Cognitive deficits (e.g., problems with memory and concentration) are not uncommon after chemotherapy, but they have not been documented systematically. In this study, we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were randomly assigned to receive either high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, and we investigated whether high-dose chemotherapy impaired cognitive functioning more than standard-dose chemotherapy.Methods: Cognitive functioning was evaluated by use of a battery of neuropsychologic tests. In addition, patients were interviewed with regard to cognitive problems, health-related quality of life, anxiety, and depression. Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy (control patients).Results: The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen, 36 patients treated with standard-dose chemotherapy plus tamoxifen, and 34 control patients. For all patients, the average time since the completion of last nonhormonal therapy was 2 years. Cognitive impairment was found in 32% of the patients treated with high-dose chemotherapy, in 17% of the patients treated with standard-dose chemotherapy, and in 9% of the control patients. In comparison with the control patients, patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment (odds ratio; 95% confidence interval [CI] = 1.8-37.7); in comparison with the patients who received standard-dose chemotherapy, this risk of impairment was 3.5-times higher (95% CI = 1.0-12.8).Conclusion: High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens. [ABSTRACT FROM AUTHOR]

Published
1998
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28. Self-perceived cognitive impairment in the first year after breast cancer and the identification of at-risk patients.

Author

Huberts AS, Albers EAC, de Ligt KM, Koppert LB, Schagen SB, and van de Poll-Franse LV

Subjects
Humans, Female, Middle Aged, Aged, Adult, Surveys and Questionnaires, Self Report, Risk Factors, Risk Assessment, Self Concept, Quality of Life, Breast Neoplasms psychology, Cognitive Dysfunction etiology
Abstract

Purpose: This study investigated self-reported clinically relevant cognitive impairment of breast cancer patients in routine clinical care and assessed factors associated with new-onset clinically relevant cognitive impairment., Methods: Cognitive functioning was assessed before start of any treatment (T0) and at 6 (T6) and 12 (T12) months after diagnosis. Cognitive functioning (CF) was measured on a scale of 0-100 with the EORTC QLQ-C30 questionnaire, and the EORTC pre-defined threshold for clinical importance. Multivariable logistic regression analyses was used to identify factors associated with new-onset clinically relevant cognitive impairment at T6 ((CF > 75 at T0 and CF < 75 at T6 and T12) or (CF > 75 at T0 and T6 and <75 at T12))., Results: Pre-treatment, 21% of patients reported clinically relevant cognitive impairment. At T12, percentage was 32%; 20% of patients reported new-onset clinically relevant cognitive impairment at T6 and/or T12. New-onset clinically relevant cognitive impairment was associated with chemo(immuno)therapy and impairment in role and emotional functioning. Younger patients and patients receiving chemo(immuno)therapy were more likely to report new-onset clinically relevant cognitive impairment post treatment., Conclusion: One in five breast cancer patients reported clinically relevant cognitive problems before start of treatment. This percentage further increased within the first year, particularly among patients treated with chemo(immuno)therapy. One in five patients reported new-onset clinically relevant cognitive impairment. Ultimately, these patients may benefit from systematic monitoring and potential referral to interventions., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Published
2024
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29. Fractionated brain X-irradiation profoundly reduces hippocampal immature neuron numbers without affecting spontaneous behavior in mice.

Author

Kuil LE, Seigers R, Loos M, de Gooijer MC, Compter A, Boogerd W, van Tellingen O, Smit AB, and Schagen SB

Abstract

Whole brain radiotherapy (WBRT) is used to improve tumor control in patients with primary brain tumors, or brain metastasis from various primary tumors to improve tumor control. However, WBRT can lead to cognitive decline in patients. We assessed whether fractionated WBRT (fWBRT) affects spontaneous behavior of mice in automated home cages and cognition (spatial memory) using the Barnes maze. Male C57Bl/6j mice received bi-lateral fWBRT at a dosage of 4 Gy/day on 5 consecutive days. In line with previous reports, immunohistochemical analysis of doublecortin positive cells in the dentate gyrus showed a profound reduction in immature neurons 4 weeks after fWBRT. Surprisingly, spontaneous behavior as measured in automated home cages was not affected. Moreover, learning and memory measured with Barnes maze, was also not affected 4-6 weeks after fWBRT. At 10-11 weeks after fWBRT a significant difference in escape latency during the learning phase, but not in the probe test of the Barnes maze was observed. In conclusion, although we confirmed the serious adverse effect of fWBRT on neurogenesis 4 weeks after fWBRT, we did not find similar profound effects on spontaneous behavior in the automated home cage nor on learning abilities as measured by the Barnes maze. The relationship between the neurobiological effects of fWBRT and cognition seems more complex than often assumed and the choice of animal model, cognitive tasks, neurobiological parameters, and experimental set-up might be important factors in these types of experiments., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sanne Schagen reports financial support for the study was provided by 10.13039/501100004622KWF. However, the KWF did not influence the design, execution or data analysis performed in this study. All other authors declare that they have no conflict of interest., (© 2024 The Authors. Published by Elsevier Ltd.)

Published
2024
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30. Artificial and natural interventions for chemotherapy- and / or radiotherapy-induced cognitive impairment: A systematic review of animal studies.

Author

Kuil LE, Varkevisser TMCK, Huisman MH, Jansen M, Bunt J, Compter A, Ket H, Schagen SB, Meeteren AYNS, and Partanen M

Subjects
Humans, Animals, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Cognitive Dysfunction prevention & control, Cancer Survivors
Abstract

Background: Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments., Methods: PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles., Results: High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes., Conclusions: Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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31. Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness.

Author

Jacobs W, Das E, and Schagen SB

Subjects
Adult, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Cognition drug effects, Cognitive Dysfunction chemically induced, Consciousness, Female, Humans, Memory drug effects, Middle Aged, Risk Factors, Stereotyping, Antineoplastic Agents adverse effects, Breast Neoplasms psychology, Cognitive Dysfunction psychology, Diagnostic Self Evaluation, Patient Education as Topic
Abstract

Objective: Information about treatment side effects can increase their occurrence; breast cancer (BC) patients showed increased cognitive problem reporting (CPR) and decreased memory performance after information about cognitive side effects. The current study extends previous research on adverse information effects (AIE) by investigating (a) risk factors, (b) underlying mechanisms and (c) an intervention to reduce AIE., Design: In an online experiment, 175 female BC patients were randomly assigned to one of three conditions. In the two experimental groups, patients were informed about the possible occurrence of cognitive problems after chemotherapy with (intervention group) or without (experimental group) reassuring information that 'there are still patients who score well on memory tests'. In the control group, no reference to chemotherapy-related cognitive problems was made., Main Outcome Measures: Main dependent measure was CPR. Four moderating and five mediating processes were examined., Results: CPR increased with higher levels of stigma consciousness in the two experimental groups, but not in the no-information control group., Conclusion: Merely informing patients about cognitive side effects may increase their occurrence, especially among individuals vulnerable to patient stereotypes. Adding reassuring information is not sufficient to reduce AIE.

Published
2017
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32. Monitoring and optimising cognitive function in cancer patients: Present knowledge and future directions.

Author

Schagen SB, Klein M, Reijneveld JC, Brain E, Deprez S, Joly F, Scherwath A, Schrauwen W, and Wefel JS

Abstract

The potentially detrimental effects of cancer and related treatments on cognitive functioning are emerging as a key focus of cancer survivorship research. Many patients with central nervous system (CNS) or non-CNS tumours develop cognitive problems during the course of their disease that can result in diminished functional independence. We review the state of knowledge on the cognitive functioning of patients with primary and secondary brain tumours at diagnosis, during and after therapy, and discuss current initiatives to diminish cognitive decline in these patients. Similarly, attention is paid to the cognitive sequelae of cancer and cancer therapies in patients without CNS disease. Disease and treatment effects on cognition are discussed, as well as current insights into the neural substrates and the mechanisms underlying cognitive dysfunction in these patients. In addition, rehabilitation strategies for patients with non-CNS disease confronted with cognitive dysfunction are described. Special attention is given to knowledge gaps in the area of cancer and cognition, in CNS and non-CNS diseases. Finally, we point to the important role for cooperative groups to include cognitive endpoints in clinical trials in order to accelerate our understanding and treatment of cognitive dysfunction related to cancer and cancer therapies.

Published
2014
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33. Cognitive functioning of postmenopausal breast cancer patients before adjuvant systemic therapy, and its association with medical and psychological factors.

Author

Schilder CM, Seynaeve C, Linn SC, Boogerd W, Beex LV, Gundy CM, Nortier JW, van de Velde CJ, van Dam FS, and Schagen SB

Subjects
Aged, Aged, 80 and over, Androstadienes adverse effects, Breast Neoplasms epidemiology, Chemotherapy, Adjuvant adverse effects, Chemotherapy, Adjuvant psychology, Cognition Disorders chemically induced, Comorbidity, Diabetes Mellitus epidemiology, Diabetes Mellitus psychology, Female, Humans, Hypertension epidemiology, Hypertension psychology, Intelligence Tests, Middle Aged, Multicenter Studies as Topic, Neuropsychological Tests, Postmenopause, Randomized Controlled Trials as Topic, Risk Factors, Tamoxifen adverse effects, Antineoplastic Agents adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms psychology, Cognition drug effects, Cognition Disorders epidemiology
Abstract

Purpose: This study aimed to identify medical and psychological predictors for cognitive performance of breast cancer (BC) patients before the start of adjuvant systemic treatment and to compare cognitive performance between BC patients and healthy controls adjusting for medical and psychological variables., Material: 205 postmenopausal BC patients underwent pre-treatment neuropsychological tests and provided medical and psychological data. 124 healthy controls underwent the same assessment., Results: 'Treatment for diabetes mellitus' and/or 'hypertension', 'less hours spent on cognitively stimulating activities', 'fewer days since surgery' and 'more reproductive years' were associated with worse cognitive performance in the BC patients, independent of age and IQ. Cognitive differences between BC patients and healthy controls could partly be explained by the evaluated variables., Conclusion: The results stress the need for adjustment for pre-treatment cognitive differences between study groups, and also indicate that further research into pre-treatment cognitive dysfunction is warranted., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Published
2010
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34. [The effect of hormone therapy on cognitive function in patients with breast cancer].

Author

Schilder CM, Linn SC, van Dam FS, and Schagen SB

Subjects
Aromatase Inhibitors administration & dosage, Female, Gonadotropin-Releasing Hormone administration & dosage, Humans, Selective Estrogen Receptor Modulators administration & dosage, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Cognition drug effects, Estrogens blood, Neoplasms, Hormone-Dependent drug therapy
Abstract

Preclinical and clinical studies suggest that oestrogens have an important role in brain functioning and cognitive ability. Given that hormone therapies for breast cancer reduce oestrogen levels or block oestrogen receptors, it is conceivable that these agents also influence cognitive function. Several small studies have been conducted to address this issue, but many of them are methodologically insufficient. The negative effects of oophorectomy and luteinising hormone-releasing hormone (LHRH) analogues on verbal memory and working memory have been demonstrated the most consistently, albeit only in small studies. Anastrozole and tamoxifen also appear to exert some negative effect on cognition, but well-designed studies are lacking. No data are available on the influence of the aromatase inhibitors exemestane and letrozole on cognitive function. Raloxifene, a drug that has no obvious advantages over tamoxifen and will likely not be developed further for breast cancer treatment, has no negative influence on cognitive functioning. It remains unclear whether the observed effects are transient or permanent, and to what extent age, menopausal status and duration of therapy influence the severity of cognitive effects.

Published
2008

35. Effects of hormonal therapy on cognitive functioning in breast cancer patients: a review of the literature.

Author

Schilder CM and Schagen SB

Subjects
Anastrozole, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Aromatase Inhibitors administration & dosage, Breast Neoplasms drug therapy, Female, Gonadotropin-Releasing Hormone administration & dosage, Humans, Neuropsychological Tests, Nitriles administration & dosage, Raloxifene Hydrochloride administration & dosage, Selective Estrogen Receptor Modulators administration & dosage, Tamoxifen administration & dosage, Triazoles administration & dosage, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms psychology, Cognition drug effects
Abstract

(Pre)clinical research suggests that estrogens play a role in brain- and cognitive functioning. It is, among others, hypothesized that estrogens have a beneficial effect on neurotransmitters that are involved in cognitive processes, protect the brain by exerting anti-inflammatory actions after ischemic injury, promote survival of brain cells, and increase cerebral blood flow and glucose transport into the brain. Neuropsychological studies suggest that natural changes in estrogen levels are associated with (small) changes in cognitive functioning, for example during the menstrual cycle. In estrogen substitution studies, however, contradicting results are found, suggesting that substitution can have both beneficial and detrimental effects on cognitive functioning. Hormonal therapy for breast carcinoma lowers estrogen levels or blocks the growth-promoting effects of estrogens. The neuropsychological studies conducted so far give, though they vary highly in design, measures and participants, some indications for effects on cognition: ovariectomy, treatment with LHRH analogues, anastrozole and tamoxifen seem to be associated with (small) negative effects on some tests. It is unclear whether those effects are reversible, and whether time on therapy is associated with the seriousness of the effects. Raloxifene, currently under study for breast cancer prevention, does not seem to have detrimental effects on cognitive functioning. For the aromatase inhibitors letrozole and exemestane no data are available yet. Because the role of hormonal therapy in breast cancer treatment is increasing, the medical grounds for prescribing are expanding and physicians can make a choice from a broad spectrum of hormonal treatments, potential effects on cognitive functioning should be part of long-term drug safety evaluations.

Published
2007

36. Neurophysiological evaluation of late effects of adjuvant high-dose chemotherapy on cognitive function.

Author

Schagen SB, Hamburger HL, Muller MJ, Boogerd W, and van Dam FS

Subjects
Alpha Rhythm drug effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Anxiety, Carboplatin administration & dosage, Chemotherapy, Adjuvant, Cognition Disorders chemically induced, Cyclophosphamide administration & dosage, Depression, Electroencephalography drug effects, Epirubicin administration & dosage, Event-Related Potentials, P300 drug effects, Evoked Potentials drug effects, Fatigue, Fluorouracil administration & dosage, Humans, Intelligence, Least-Squares Analysis, Middle Aged, Neuropsychological Tests, Thiotepa administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms psychology, Cognition drug effects
Abstract

Objectives: To evaluate late neurotoxicity of adjuvant high-dose (HD) chemotherapy versus standard-dose (SD) chemotherapy by event-related potentials (ERP) and quantitative electroencephalography (qEEG)., Patients and Methods: From a randomized study in high-risk breast cancer patients on the efficacy of high-dose versus standard-dose adjuvant chemotherapy, late effects on cognitive functioning were analyzed by neuropsychological tests. Cognitive impairment was found in 32% of the HD group, 17% of the SD group and in 9% of a control group of stage I breast cancer patients not treated with chemotherapy. In 17 consecutive patients in the HD group and 16 consecutive patients in the SD group neurophysiological tests were performed, consisting of P300 and qEEG. Results of patients treated with chemotherapy were compared with results of 14 control patients not treated with chemotherapy. All patients were tested two years after treatment., Results: Asymmetry of the alpha rhythm of > or =0.5 Hz was found in 7 HD patients, 2 SD patients and in none of the control patients (p = 0.01). No differences were found between the groups with regard to frequency of alpha rhythm, alpha blocking and latency of P300. No correlation was found between neurophysiological parameters and neuropsychological performance, except for an overall relation between the P300 latencies and the total number of deviant test scores., Conclusion: Although the neurophysiological differences are subtle and the relation with the cognitive functioning in individual patients as measured by the neuropsychological examination is equivocal, the results suggest that there is neurophysiological support for cognitive dysfunction as a late complication of high-dose systemic chemotherapy in breast cancer.

Published
2001
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37. Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy.

Author

van Dam FS, Schagen SB, Muller MJ, Boogerd W, vd Wall E, Droogleever Fortuyn ME, and Rodenhuis S

Subjects
Adult, Anxiety, Breast Neoplasms psychology, Cognition Disorders psychology, Depression, Female, Humans, Middle Aged, Neuropsychological Tests, Odds Ratio, Prevalence, Quality of Life, Risk, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms drug therapy, Cognition Disorders chemically induced
Abstract

Background: Although high-dose chemotherapy is rapidly gaining acceptance as a treatment option for a number of cancers, the long-term toxic effects of such therapy are a concern. Cognitive deficits (e.g., problems with memory and concentration) are not uncommon after chemotherapy, but they have not been documented systematically. In this study, we assessed the prevalence of cognitive deficits in a group of patients with high-risk breast cancer who were randomly assigned to receive either high-dose or standard-dose adjuvant chemotherapy plus tamoxifen, and we investigated whether high-dose chemotherapy impaired cognitive functioning more than standard-dose chemotherapy., Methods: Cognitive functioning was evaluated by use of a battery of neuropsychologic tests. In addition, patients were interviewed with regard to cognitive problems, health-related quality of life, anxiety, and depression. Results from patients who received adjuvant systemic therapy were compared with results from patients who had early stage breast cancer not treated with such therapy (control patients)., Results: The study population consisted of 34 patients treated with high-dose chemotherapy plus tamoxifen, 36 patients treated with standard-dose chemotherapy plus tamoxifen, and 34 control patients. For all patients, the average time since the completion of last nonhormonal therapy was 2 years. Cognitive impairment was found in 32% of the patients treated with high-dose chemotherapy, in 17% of the patients treated with standard-dose chemotherapy, and in 9% of the control patients. In comparison with the control patients, patients treated with high-dose chemotherapy appeared to have an 8.2-times higher risk of cognitive impairment (odds ratio; 95% confidence interval [CI] = 1.8-37.7); in comparison with the patients who received standard-dose chemotherapy, this risk of impairment was 3.5-times higher (95% CI = 1.0-12.8)., Conclusion: High-dose chemotherapy appears to impair cognitive functioning more than standard-dose chemotherapy. Central nervous system toxicity may be a dose-limiting factor in high-dose chemotherapy regimens.

Published
1998
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