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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]

Background: In the field of clinical neuropsychology, researchers and clinicians often use predefined criteria to determine whether there are indications of cognitive impairment. However, corrections and expected false-positive rates are typically available only for uncorrelated tests and simple consensus criteria. Objective: To present an easy-to-use and freely available online tool as a solution for scenarios involving correlated tests and composite consensus criteria, as frequently encountered in clinical neuropsychological research and practice. Method: Our tool employs Monte Carlo simulations to account for the number of participants, thus addressing the uncertainty in estimating false positive rates with small samples. We demonstrate the tool's utility through an example involving cognitive impairment assessment in cancer patients after chemotherapy. Results: The tool reveals considerable uncertainty in false positive rates, especially with small sample sizes, where rates may be higher than traditionally assumed. We found that correlations between tests affect impairment rates differently depending on whether single or multiple test criteria are used. For single-test criteria, lower correlations are associated with more false positives, while for multiple-test criteria, lower correlations lead to fewer false positives. Conclusions: This innovative tool enables more accurate estimation of false positive rates in various neuropsychological conditions. By providing a user-friendly interface and accounting for real-world complexities such as test correlations and composite criteria, our tool empowers clinicians and researchers to: Make informed decisions when interpreting neuropsychological test results.Design more robust research protocols for cognitive impairment studies.Better understand the implications of sample size on false positive rates.

Introduction: Tamoxifen may adversely affect cognitive function by interfering with estrogen action in the brain. Despite growing evidence for a relationship between tamoxifen and cognitive problems, findings remain inconclusive. While some tamoxifen-related side effects seem exposure-dependent with concentrations of tamoxifen or its main metabolite, endoxifen, this has never been investigated for cognitive function. We investigated cognitive function after two years of tamoxifen and its association with tamoxifen and endoxifen exposure., Methods: 135 women with breast cancer completed the Amsterdam Cognition Scan (ACS), an online neuropsychological test battery, after two years of tamoxifen. Test scores were converted to standardized Z-scores based on a matched 'no-cancer' control group. Tamoxifen and endoxifen concentrations and tamoxifen dose were regressed separately on cognitive functioning., Results: Patients reported mild cognitive complaints and had worse verbal learning, processing speed, executive functioning, and motor functioning compared to matched controls. After correcting for age, mean tamoxifen and endoxifen levels, as well as tamoxifen dose, were associated with worse performance on several cognitive domains., Conclusion: Tamoxifen is adversely associated with objective as well as self-reported cognitive function, which may depend on the level of exposure to tamoxifen and endoxifen. Further research is warranted to confirm this hypothesis., Competing Interests: Competing interests: The authors declare no conflict of interest. Ethics approval and consent to participate: This study was approved by the Medical Ethics Committee of the Erasmus Medical Center (MEC 2017-548) and was performed according the Declaration of Helsinki. All patients provided written informed consent., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: To investigate the proportion of patients with lymphoma with persistent clinically relevant cognitive impairment, and its relation to  treatment, fatigue, and psychological distress., Methods: Patients with diffuse-large-B-cell-lymphoma (DLBCL), follicular-lymphoma (FL), and chronic-lymphocytic-leukemia (CLL)/small-lymphocytic-lymphoma (SLL), diagnosed between 2004-2010 or 2015-2019, were followed up to 8 years post-diagnosis. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry and the Population-based HAematological Registry for Observational Studies. The EORTC QLQ-C30 was used to assess cognitive functioning and fatigue, and the HADS to assess psychological distress. Individual growth curve models were performed. Results were compared with an age- and sex-matched normative population., Results: A total of 924 patients were included (70% response rate). Persistent cognitive impairment was twice as high in patients (30%) compared to the normative population (15%). Additionally, 74% of patients reported co-occurring symptoms of persistent fatigue and/or psychological distress. Patients with FL (- 23 points, p < 0.001) and CLL/SLL (- 10 points, p < 0.05) reported clinically relevant deterioration of cognitive functioning, as did the normative population (FLnorm - 5 points, DLBCLnorm - 4 points, both p < 0.05). Younger age, higher fatigue, and/or psychological distress at inclusion were associated with worse cognitive functioning (all p's < 0.01). Treatment appeared less relevant., Conclusion: Almost one-third of patients with lymphoma report persistent cognitive impairment, remaining present up to 8 years post-diagnosis. Early onset and co-occurrence of symptoms highlight the need for clinicians to discuss symptoms with patients early., Implications for Cancer Survivors: Early recognition of cognitive impairment could increase timely referral to suitable supportive care (i.e., lifestyle interventions) and reduce (long-term) symptom burden., Competing Interests: Declarations. Ethics approval: Ethical approval for the study was obtained from a certified Medical Ethics Committee (Maxima Medical Centre in Veldhoven, the Netherlands; 0734). Competing interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Many patients with a malignant (i.e., grade II-IV) glioma are of working age, yet they are rarely included in "cancer and work" studies. Here, we explored (1) the work-related experiences and unmet needs of patients with a malignant glioma and (2) the experiences and needs of relevant healthcare and occupational (health) professionals ("professionals") in providing work-related support to this patient group., Methods: Individual semi-structured interviews were held with patients with a malignant glioma who were of working age and had an employment contract at diagnosis, and relevant professionals. Interviews were transcribed verbatim and analysed thematically., Results: Patients (n = 22) were on average 46 ± 13 years of age (64% male) and diagnosed with a grade II (n = 12), III (n = 4), or IV glioma (n = 6). Professionals (n = 16) had on average 15 ± 9 years of relevant work experience with the patient group. Four themes emerged from the data: (1) having a malignant glioma: experienced consequences on work ability, (2) communicating about the consequences of a malignant glioma at work, (3) distilling the right approach: generic or tailored work-related support, and (4) accessibility of work-related support., Conclusions: Glioma-specific consequences on patients' work ability necessitate better communication between, and tailored guidance for, patients, relevant professionals, and the workplace. Suggestions for improvement, e.g., the periodic use of comprehensive neuropsychological assessments, are provided in the article., Implications for Cancer Survivors: Patients with a malignant glioma would benefit from tailored and proactive outreach about work-related issues bv relevant professionals., Competing Interests: Declarations. Competing interests: Three co-authors (Desiree Dona, Sanne Schagen, Filip de Vos) were interviewed as professionals within this study. The interviewed professionals were not part of the treatment team of the interviewed patients. The authors have no other (potential) competing interests to declare. Ethics approval: The Medical Ethics Committees of the participating hospitals declared that the study was not subject to the Dutch Medical Research Involving Human Subjects Act. All procedures were in accordance with the ethical standards of the responsible committees and with the Helsinki Declaration of 1975, as revised in 2000. Consent to participate: Written informed consent was obtained from all individual interviewees included in the study., (© 2023. The Author(s).)

Physical exercise is a promising intervention to improve brain white matter integrity. In the PAM study, exercise intervention effects on white matter integrity were investigated in breast cancer patients. Chemotherapy-treated breast cancer patients with cognitive problems were randomized 2-4 years post-diagnosis to an exercise (n = 91) or control group (n = 90). The 6-month exercise intervention consisted of four hours/week of aerobic and resistance training. White matter integrity was measured at baseline and 6-month follow-up with fractional anisotropy (FA) and mean diffusivity (MD), which were derived from magnetic resonance diffusion tensor imaging (DTI). Both DTI metrics were analyzed whole brain and voxel-wise with a modified tract based spatial statistics (TBSS) procedure. Other measurements included cognition and physical fitness. Exercise effects were analyzed with multiple regression analyses. An explorative analysis was conducted in highly fatigued patients. DTI scans were available for 69 patients of the intervention (age = 52.3 ± 8.9yrs.) and 72 patients of the control group (age = 53.2 ± 8.6yrs.). Whole brain and voxel-wise analyses revealed no significant intervention effects on FA and MD. In highly fatigued patients (exercise: n = 32; control: n = 24), significant clusters of decreased FA post-intervention were observed in the left inferior and superior longitudinal fasciculus. Mean FA in these clusters was not predictive of cognition. A 6-month exercise intervention did not affect white matter integrity in chemotherapy-treated breast cancer patients. However, in highly fatigued breast cancer patients a significant FA decrease was observed post-intervention. The direction of these results is unexpected, and more research is needed to further understand these results., Competing Interests: Declarations: The study was approved by the Medical Ethics Committee of the UMCU and all patients provided written informed consent before baseline measurements. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To evaluate the process of an online cognitive rehabilitation program aimed at supporting cancer survivors experiencing cognitive problems at work., Methods: Cancer survivors (n = 279) were randomized to one of the intervention groups (i.e., basic and extensive online cognitive rehabilitation) or waitlist control group. Recruitment, reach, dosage, implementation, perceived usefulness and experiences with the program were evaluated using questionnaires and logbooks., Results: Implementation (i.e., reach multiplied by dosage) was acceptable for both versions of the program (range 63% to 76%). Cancer survivors and cognitive therapists perceived the overall program as moderately to highly useful and generally reported positive experiences., Conclusions: Both a basic and extensive version of the online cognitive rehabilitation program were successfully implemented in the context of an RCT, suggesting their feasibility as intervention to support cancer survivors with cognitive problems at work., Competing Interests: Conflict of Interests: The authors declare that they have no conflict of interest., (Copyright © 2025 American College of Occupational and Environmental Medicine.)

Background: Cognitive decline is an arising concern in patients who need cranial irradiation. We used the pooled longitudinal individual patient data of two phase III trials: NCT01780675 and PREMER to investigate whether hippocampal avoidance (HA)-PCI is associated with improved self-reported cognitive functioning (SRCF) compared with PCI without increasing brain metastases (BM) development within the HA area., Methods: Patients with stage I-IV small cell lung cancer (SCLC) were randomized to PCI or HA-PCI. SRCF was assessed and contrast enhanced brain magnetic resonance imaging (MRI) was performed at baseline and up to 24 months follow-up. SRCF and BM incidence after (HA)-PCI were compared between arms. Self reported cognitive impairment was defined as SCRF < 75., Results: In total, 318 patients were randomized. Longitudinal generalized estimating equation (GEE) analysis showed that HA-PCI neither had a significant impact on SRCF (β = 1.41, p = 0.52) nor on cognitive impairment (OR 0.81, 95 %CI 0.53-1.25, p = 0.34). The median follow up was 41.7 (95 %CI 35.7-47.6) months, during which 61 patients developed BM (PCI arm: 30, HA-PCI arm: 31, p = 0.9). BM site was solitary in 15 patients (PCI arm: 7, HA-PCI arm: 8, p = 0.8). Nine of the 61 patients had BM within the HA area (PCI arm: 4, HA-PCI arm: 5, p = 1.0). The BM incidence was not significantly different between arms (subdistribution hazard ratio [sHR] 1.03, 95 %CI 0.62-1.70, p = 0.91)., Conclusion: HA-PCI did not preserve longitudinal SRCF but did also not increase the risk of BM. Additional strategies should be investigated to further improve the therapeutic ratio of PCI., Trials Registration: ClinicalTrials.gov (NCT01780675) ClinicalTrials.gov (NCT02397733)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: N Rodríguez de Dios: Consulting or Advisory Role: AstraZeneca Spain. Speakers' Bureau: AstraZeneca Spain, Siemens Healthineers. F Couñago: Honoraria: AstraZeneca, Astellas Pharma. L Hendriks: No related COI. Outside of this manuscript personal fees as an invited speaker from Benecke, Medtalks and VJOncology; personal fees for participation in mentorship programme funded by AstraZeneca; personal fees for travel support from Roche; personal fees as member of the committee that revised the Dutch guidelines on NSCLC, brain metastases and leptomeningeal metastases; fees paid to her institution for an educational webinar from Janssen; fees paid to her institution for advisory board membership from Amgen, BMS, Boehringer Ingelheim, Janssen, Lilly, Merck, MSD, Novartis, Pfizer, Roche and Takeda; fees paid to her institution as an invited speaker from AstraZeneca, Bayer, high5oncology, Lilly and Merck Sharp & Dohme (MSD); fees paid to her institution for interview sessions from Roche; fees paid to her institution for podcast appearance from Takeda; institutional research grants from AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Merck and Pfizer (Novartis under negotiation); institutional funding as a local principal investigator (PI) from AbbVie, AstraZeneca, Blueprint Medicines, Gilead, GlaxoSmithKline (GSK), Merck Serono, Mirati, MSD, Novartis, Roche and Takeda; non-remunerated roles as chair for metastatic NSCLC of the lung cancer group for EORTC (European Organisation for Research and Treatment of Cancer) and as the secretary of the studies foundation for NVALT (Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose). The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) is proposed to reduce neurocognitive decline, while preserving the benefits of PCI. We evaluated whether (HA-)PCI induces changes in white matter (WM) microstructure and whether sparing the hippocampus has an impact on preserving brain network topology. Additionally, we evaluated associations between topological metrics with hippocampal volume and neuropsychological outcomes., Methods: In this multicenter randomized phase 3 trial (NCT01780675), small cell lung cancer (SCLC) patients underwent neuropsychological testing and diffusion tensor imaging (DTI) before, 4 months (33 PCI, 37 HA-PCI) and 1 year (19 PCI, 17 HA-PCI) after (HA-)PCI. Changes in WM microstructure were investigated using whole-brain voxel-based analysis of fractional anisotropy (FA) and mean diffusivity (MD). Both hippocampal and whole-brain graph measures were used to evaluate the topological organization of structural networks. Correlation analysis was performed to associate topological metrics with neuropsychological outcomes and hippocampal volume., Results: Both HA-PCI and PCI were associated with decreased FA in major WM tracts, such as the corpus callosum, at 4 months and 1 year post-treatment. While these FA decreases did not differ significantly between treatment groups, only PCI demonstrated increased MD over time. Additionally, PCI showed decreased global efficiency and increased characteristic path length over time when compared to HA-PCI. Significant correlations were found between whole-brain graph measures and neuropsychological outcomes., Conclusion: While both techniques induce important changes in the WM microstructure, HA-PCI might better preserve the topological organization of brain networks than PCI. The neuroprotective role of hippocampal sparing still needs further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.)

Purpose: This individual participant data meta-analysis (IPD-MA) assesses exercise effects on self-reported cognitive functioning (CF) and investigates whether effects differ by patient-, intervention-, and exercise-related characteristics., Methods: IPD from 16 exercise RCTs, including 1987 patients across multiple types of non-metastatic cancer, was pooled. A one-stage IPD-MA using linear mixed-effect models was performed to assess exercise effects on self-reported CF (z-score) and to identify whether the effect was moderated by sociodemographic, clinical, intervention- and exercise-related characteristics, or fatigue, depression, anxiety, and self-reported CF levels at start of the intervention (i.e., baseline). Models were adjusted for baseline CF and included a random intercept at study level to account for clustering of patients within studies. A sensitivity analysis was performed in patients who reported cognitive problems at baseline., Results: Minimal significant beneficial exercise effects on self-reported CF (β=-0.09 [-0.16; -0.02]) were observed, with slightly larger effects when the intervention was delivered post-treatment (n=745, β=-0.13 [-0.24; -0.02]), and no significant effect during cancer treatment (n=1,162, β=-0.08 [-0.18; 0.02]). Larger effects were observed in interventions of 12 weeks or shorter (β=-0.14 [-0.25; -0.04]) or 24 weeks or longer (β=-0.18 [-0.32; -0.02]), whereas no effects were observed in interventions of 12-24 weeks (β=0.01 [-0.13; 0.15]). Exercise interventions were most beneficial when provided to patients without anxiety symptoms (β=-0.10 [-0.19; -0.02]) or after completion of treatment in patients with cognitive problems (β=-0.19 [-0.31; -0.06]). No other significant moderators were identified., Conclusions: This cross-cancer IPD meta-analysis observed small beneficial exercise effects on self-reported CF when the intervention was delivered post-treatment, especially in patients who reported cognitive problems at baseline., Implications for Cancer Survivors: This study provides some evidence to support the prescription of exercise to improve cognitive functioning. Sufficiently powered trials are warranted to make more definitive recommendations and include these in the exercise guidelines for cancer survivors., (© 2023. The Author(s).)

Purpose: It is assumed that a segment of breast cancer survivors are cognitively affected after chemotherapy. Our aim is to discover whether there is a qualitatively different cognitively affected subgroup of breast cancer survivors, or whether there are only quantitative differences between survivors in cognitive functioning., Methods: Latent profile analysis was applied to age-corrected neuropsychological data -measuring verbal memory, attention, speed, and executive functioning- from an existing sample of 62 breast cancer survivors treated with chemotherapy. Other clustering methods were applied as sensitivity analyses. Subgroup distinctness was established with posterior mean assignment probability and silhouette width. Simulations were used to calculate subgroup stability, posterior predictive checks to establish absolute fit of the subgrouping model. Subgrouping results were compared to traditional normative comparisons results., Results: Two subgroups were discovered. One had cognitive normal scores, the other -45%- had lower scores. Subgrouping results were consistent across clustering methods. The subgroups showed some overlap; 6% of survivors could fall in either. Subgroups were stable and described the data well. Results of the subgroup clustering model matched those of a traditional normative comparison method requiring small deviations on two cognitive domains., Conclusions: We discovered that almost half of breast cancer survivors after chemotherapy form a cognitively affected subgroup, using a data-driven approach. This proportion is higher than previous studies using prespecified cutoffs observed., Implications for Cancer Survivors: A larger group of cancer survivors may be cognitively affected than previously recognized, and a less strict threshold for cognitive problems may be needed in this population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Several observational studies have described an inverse association between cancer diagnosis and subsequent dementia risk. Multiple biologic mechanisms and potential biases have been proposed in attempts to explain this association. One proposed explanation is the opposite expression of Pin1 in cancer and dementia, and we use this explanation and potential drug target to illustrate the required assumptions and potential sources of bias for inferring an effect of Pin1 on dementia risk from analyses measuring cancer diagnosis as a proxy for Pin1 expression., Methods: We used data from the Rotterdam Study, a population-based cohort. We estimate the association between cancer diagnosis (as a proxy for Pin1) and subsequent dementia diagnosis using two different proxy methods and with confounding and censoring for death addressed with inverse probability weights. We estimate and compare the complements of a weighted Kaplan-Meier survival estimator at 20 years of follow-up., Results: Out of 3634 participants, 899 (25%) were diagnosed with cancer, of whom 53 (6%) had dementia, and 567 (63%) died. Among those without cancer, 15% (411) were diagnosed with dementia, and 667 (24%) died over follow-up. Depending on the confounding and selection bias control, and the way in which cancer was used as a time-varying proxy exposure, the risk ratio for dementia diagnosis ranged from 0.71 (95% confidence interval [CI] = 0.49, 0.95) to 1.1 (95% CI = 0.79, 1.3)., Conclusion: Being explicit about the underlying mechanism of interest is key to maximizing what we can learn from this cancer-dementia association given available or readily collected data, and to defining, detecting, and preventing potential biases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking., Purpose: Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes relate to memory function., Study Type: Prospective., Population: A total of 181 chemotherapy-treated stage I-III breast cancer patients with cognitive problems and relatively low physical activity levels (≤150 minutes moderate to vigorous physical activity per week), divided into an exercise (N = 91) or control group (N = 90)., Field Strength/sequence: Two-dimensional echo planar pseudo-continuous arterial spin labeling CBF sequence at 3 T., Assessment: The 6-month long intervention consisted of (supervised) aerobic and strength training, 4 × 1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after 6 months included gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Physical fitness and memory function were also assessed. Subgroup analyses were performed in patients with high fatigue levels at baseline., Statistical Tests: Multiple regression analyses with a two-sided alpha of 0.05 for all analyses., Results: There was a significant improvement in physical fitness (VO 2peak in mL/minute/kg) in the intervention group (N = 53) compared to controls (N = 51, β = 1.47 mL/minute/kg, 95% CI: 0.44-2.50). However, no intervention effects on CBF were found (eg, whole brain: P = 0.565). Highly fatigued patients showed larger but insignificant treatment effects on CBF (eg, whole brain: P = 0.098). Additionally, irrespective of group, a change in physical fitness was positively associated with changes in CBF (eg, whole brain: β = 0.75, 95% CI: 0.07-1.43). There was no significant relation between CBF changes and changes in memory performance., Data Conclusion: The exercise intervention did not affect CBF of cognitively affected breast cancer patients. A change in physical fitness was associated with changes in CBF, but changes in CBF were not associated with memory functioning., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 5., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Cancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce., Methods: This is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cognitive complaints. Cognitive performance was compared to normative data and expressed as age-adjusted z-scores., Results: A total of 143 patients participated in the online cognitive testing. Overall, cognitive performance was mildly impaired on some, but not all, cognitive domains, with no significant differences between groups. Clinically relevant cognitive impairment was present in 25% to 40% of all participants, regardless of study group. We observed no statistically significant effect of exercise, or being physically active during chemotherapy, on long-term cognitive performance or self-reported cognition, except for the task reaction time, which favored the control group (β = -2.04, 95% confidence interval: -38.48; -2.38). We observed no significant association between self-reported higher physical activity levels during chemotherapy or at follow-up and better cognitive outcomes., Conclusion: In this pragmatic follow-up study, exercising and being overall more physically active during or after adjuvant chemotherapy for breast cancer was not associated with better tested or self-reported cognitive functioning, on average, 8.5 years after treatment. Future prospective studies are needed to document the complex relationship between exercise and CRCI in cancer survivors., (© 2024. The Author(s).)

Purpose: Breast cancer patients receiving chemotherapy can develop cognitive impairment. There is no gold standard for defining cognitive impairment. We applied the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) to determine its prevalence in breast cancer patients receiving adjuvant chemotherapy and examine differences between patients with and without MCI., Methods: We used pre-existing cognitive data on 5 neuropsychological test outcomes (verbal memory, processing speed, executive functioning, and verbal fluency) gathered from 240 breast cancer patients who received adjuvant conventional (n = 154) or high-dose chemotherapy (n = 86). Assessments occurred 6 or 12 months post-chemotherapy and results were compared with data from 66 women without cancer. MCI was defined by the following: (i) presence of concern regarding a change in cognition, (ii) impairment in one or more cognitive tests (1.5 standard deviation below a normative mean), (iii) preservation of independence in functional abilities, and (iv) the absence of dementia., Results: Twenty percent (n = 49) of breast cancer patients who received chemotherapy (conventional therapy n = 29 (12%), high-dose therapy = 20 (8.3%)) met the criteria for MCI, compared with 7.6% (n = 5) of controls. Prevalence was significantly different between patients and controls (P = 0.020, and corrected for IQ P < 0.001). Patients with MCI had significant lower education levels (P < 0.002) and premorbid IQ (P = 0.001) compared with patients without MCI., Conclusions: Twenty percent of breast cancer patients treated with chemotherapy met NIA-AA criteria for MCI, compared with 7.6% of the controls., Implications for Cancer Survivors: These criteria, which include formal test performance as well as a person's symptoms and functional status, can be useful in clinical practice and scientific research., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Purpose: To assess cognitive functioning in occupationally active non-central nervous system cancer survivors with cognitive complaints using neuropsychological tests, and to investigate the association between (1) formally assessed cognitive functioning and self-reported work-related outcomes and (2) self-reported cognitive functioning at work and self-reported work-related outcomes., Methods: Baseline data of a multicenter, randomized controlled trial (n = 279) were used. Associations between neuropsychological test performance (Amsterdam Cognition Scan) and self-reported cognitive functioning (Cognitive Symptom Checklist-work) with work ability (Work Ability Index) and work functioning (Work Role Functioning Questionnaire) were examined using multivariate linear regression., Results: Thirty percent of cancer survivors had lower than expected performance on neuropsychological tests. Higher overall neuropsychological test performance was associated with better work ability (Cohen's f 2  = 0.014) and physical functioning at work (Cohen's f 2  = 0.13). Furthermore, higher motor performance was associated with better work ability (Cohen's f 2  = 0.018). In addition, self-reported work-related cognitive complaints were associated with self-reported work-related outcomes (Cohen's f 2  = 0.13-0.35)., Conclusions: The percentage of cancer survivors with lower than expected performance on neuropsychological tests exceeded the percentage expected in a normal population. This neuropsychological test performance was weakly associated with various aspects of work ability and work functioning. Stronger associations were found between self-reported cognitive functioning at work with self-reported work-related outcomes., Implications for Cancer Survivors: A cognitive rehabilitation approach that specifically aims at reducing cognitive symptoms at work could be a valuable part of interventions that aim to improve work-related outcomes. Trial registration The study is registered at ClinicalTrials.gov (NCT03900806) at 03 April 2019 (current status: ongoing), https://clinicaltrials.gov/ct2/show/NCT03900806?term=NCT03900806&draw=2&rank=1., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Background: Cognitive problems contribute to decline in work performance. We evaluated (1) the effectiveness of basic self-management and extensive therapist-guided online cognitive rehabilitation on attainment of individually predetermined work-related goals among occupationally active cancer survivors, and (2) whether effectiveness of the programs differed for survivors with and without formal cognitive impairment., Methods: In a 3-arm randomized controlled trial (NCT03900806), 279 non-central nervous system cancer survivors with cognitive complaints were assigned to the basic program (n = 93), the extensive program (n = 93), or a waiting-list control group (n = 93). Participants completed measurements pre-randomization (T0), 12 weeks post-randomization upon program completion (T1), and 26 weeks post-randomization (T2). Mixed-effects modeling was used to compare intervention groups with the control group on goal attainment, and on self-perceived cognitive problems, work ability, and health-related quality of life., Results: Participants in the extensive program achieved their predetermined goals better than those in the control group, at short- and long-term follow-up (effect size [ES] = .49; P < .001; ES = .34; P = .014). They also had fewer recovery needs after work (ES = -.21; P = .011), more vitality (ES = .20; P = .018), and better physical role functioning (ES = .0.43 P = .015) than controls. At long-term follow-up, this finding persisted for physical role functioning (ES = .42; P = .034). The basic program elicited a small positive nonsignificant short-term (not long-term) effect on goal attainment for those with adequate adherence (ES = .28, P = .053). Effectiveness of the programs did not differ for patients with or without cognitive impairment., Conclusions: Internet-based therapist-guided extensive cognitive rehabilitation improves work-related goal attainment. Considering the prevalence of cognitive problems in survivors, it is desirable to implement this program., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: The Cognitive Symptom Checklist-Work (CSC-W) is a self-report measure to assess cognitive symptoms (i.e., memory and executive function) in working adults with cancer. To date, general working population norm data are lacking worldwide. We established CSC-W norm values in the general working population, and assessed associations of CSC-W scores with work and health-related factors., Methods: This cross-sectional study consisted of 1,000 Dutch working adults, of whom data was collected through an online respondent panel. The sample was stratified for sex and age, and data were weighted. Summary scores of the CSC-W total scale, and memory and executive function symptoms subscales, were determined (e.g., means, percentiles). Z- and T-scores were calculated, and analysis of (co)variance has been applied., Results: Cognitive symptom scores were relatively stable across age groups, but 18-39-year-old respondents reported lower memory and executive function than respondents in other age groups. Symptom scores of memory function (mean 29.1; SD = 16.7) were higher for all age groups and in both sexes compared to executive function (mean 22.1; SD = 16.8). No sex differences in memory and executive function were observed. Higher symptom scores were associated with performing non-manual work only, manual work only, self-reported long-term illness, and higher levels of depressive symptoms and fatigue., Conclusion: The CSC-W norms may enhance the interpretation and facilitate the analysis of self-reported cognitive symptoms in patients with cancer at work. Our findings may support health care professionals in identifying working adults with cancer with cognitive symptoms and in developing personalized treatment., (© 2023. The Author(s).)

Purpose: This study aimed to assess health-related quality of life (HRQoL) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and to identify factors associated with this., Methods: HRQoL was measured pre-SRS, at 3- and 6-month follow-up. Physical functioning, cognitive functioning, role functioning, and fatigue were analyzed with the EORTC QLQ-C30 questionnaire. Motor dysfunction, future uncertainty, visual disorder, communication deficit, and headaches were analyzed with the EORTC QLQ-BN20. Clinically important symptom or functional impairment was assessed following set thresholds. Factors associated with impairment were identified through multivariable logistic regression analyses., Results: At baseline, 178 patients were included; 54% (n=96) completed questionnaires at 3 months and 39% (n=70) at 6 months. Before SRS, 29% of linear accelerator (LINAC) patients reported physical and cognitive impairment, while 25% reported impairment for fatigue. At 6 months, 39%, 43%, and 57% of LINAC patients reported impairment respectively. Forty-five percent of Gamma Knife (GK) patients reported impairment pre-SRS for physical, cognitive functioning, and fatigue. At 6 months, 48%, 43%, and 33% of GK patients reported impairment respectively. Except for role functioning, pre-SRS symptom and functioning scores were associated with impairment at 3 months, whereas scores at 3 months were associated with impairment at 6 months. Age, gender, systemic therapy, and intracranial progression were not associated with clinically important impairment., Conclusion: As 33-57% of patients with brain metastases reported symptom burden and functional impairments that were of clinical importance, it is recommended to pay attention to the HRQoL outcomes of these patients during clinical encounters., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Verbal memory is a complex and fundamental aspect of human cognition. However, traditional sum-score analyses of verbal learning tests oversimplify underlying verbal memory processes. We propose using process models to subdivide memory into multiple processes, which helps in localizing the most affected processes in impaired verbal memory. Additionally, the model can be used to address score and process variability. This study aims to investigate the effects of cancer and its treatment on verbal memory, as well as provide a demonstration of how process models can be used to investigate the uncertainty in neuropsychological test scores., Method: We present an investigation of memory process scores in non-CNS cancer survivors ( n  = 184) and no-cancer controls ( n  = 204). The participants completed the Amsterdam Cognition Scan (ACS), in which classical neuropsychological tests are digitally recreated for online at-home administration. We analyzed data from the ACS equivalent of a Verbal Learning Test using both traditional sum scores and a Bayesian process model., Results: Analysis of the sum score indicated that patients scored lower than controls on immediate recall but found no difference for delayed recall. The process model analysis indicated a small difference between patients and controls in immediate retrieval from both the partially learned and learned states, with no differences in learning or delayed retrieval processes. Individual-level analysis shows considerable uncertainty for sum scores. Sum scores were more certain than single trials. Retrieval parameters also showed less uncertainty than learning parameters., Conclusion: The Bayesian process model increased the informativity of Verbal Learning test data, by showing uncertainty of the traditional sum score measurements as well as how the underlying processes differed between populations. Additionally, the model grants insight into underlying memory processes for individuals and how these processes vary within and between them.

Objective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO., Design: A cross-sectional study with prospective follow-up, nested in a nationwide cohort., Setting: Multicentre in the Netherlands., Population or Sample: 641 women (66% BRCA1/2 pathogenic variant carriers) who underwent either a premenopausal RRSO ≤ age 45 (n = 436) or a postmenopausal RRSO ≥ age 54 (n = 205). All participants were older than 55 years at recruitment., Methods: Participants completed an online cognitive test battery and a questionnaire on subjective cognition. We used multivariable regression analyses, adjusting for age, education, breast cancer, hormone replacement therapy, cardiovascular risk factors and depression., Main Outcome Measures: The influence of RRSO on objective and subjective cognition of women with a premenopausal RRSO compared with women with a postmenopausal RRSO., Results: After adjustment, women with a premenopausal RRSO (mean time since RRSO 18.2 years) performed similarly on objective cognitive tests compared with women with a postmenopausal RRSO (mean time since RRSO 11.9 years). However, they more frequently reported problems with reasoning (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.1-3.1) and multitasking (OR 1.9, 95% CI 1.1-3.4) than women with a postmenopausal RRSO. This difference between groups disappeared in an analysis restricted to women of comparable ages (60-70 years)., Conclusions: Reassuringly, approximately 18 years after RRSO, we found no association between premenopausal RRSO and objective cognition., (© 2023 John Wiley & Sons Ltd.)

Purpose: Cognitive symptoms affect cancer survivors' functioning at work. To date, cognitive symptoms trajectories in working cancer survivors and the factors associated with these trajectories have not been examined., Methods: Data from a heterogeneous group of working cancer survivors (n = 379) of the longitudinal "Work-Life-after-Cancer" study, linked with Netherlands Cancer Registry data, were used. The Cognitive Symptom Checklist-Work was administered at baseline (within the first 3 months after return to work), 6-, 12-, and 18-month follow-up to measure self-perceived memory and executive function symptoms. Data were analyzed using group-based trajectory modeling., Results: Four trajectories of memory and executive function symptoms were identified. All memory symptoms trajectories were stable and labeled as "stable-high" (15.3% of the sample), "stable-moderately high" (39.6%), "stable-moderately low" (32.0%), and "stable-low" (13.0%). Executive function symptoms trajectories changed over time and were labeled as "increasing-high" (10.1%), "stable-moderately high" (32.0%), "decreasing-moderately low" (35.5%), and "stable-low" (22.4%). Higher symptoms trajectories were associated with older age, longer time from diagnosis to return to work, more quantitative work demands, and higher levels of depressive symptoms at baseline., Conclusions: In cancer survivors who returned to work, four cognitive symptoms trajectory subgroups were identified, representing different but relatively stable severity levels of cognitive symptoms., Implications for Cancer Survivors: To identify cancer survivors with higher symptoms trajectories, health care providers should assess cognitive symptoms at baseline after return to work. In case of cognitive symptoms, it is important to also screen for psychological factors to provide appropriate guidance., (© 2022. The Author(s).)

Introduction: In the randomized controlled trial in patients with SCLC comparing standard prophylactic cranial irradiation (PCI) with hippocampal avoidance PCI (HA-PCI), we did not observe beneficial effects of HA-PCI on tested cognition. Here, we report findings on self-reported cognitive functioning (SRCF) and quality of life (QoL)., Methods: Patients with SCLC were randomized to receive PCI with or without HA (NCT01780675) and assessed at baseline (82 HA-PCI and 79 PCI patients) and at 4, 8, 12, 18, and 24 months of follow-up, using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-brain cancer module (BN20). SRCF was assessed with the cognitive functioning scale of the EORTC QLQ-C30 and the Medical Outcomes Study questionnaire. A change of 10 points was used for minimal clinically important differences. Percentages of patients classified with having improved, stable, or deteriorated SRCF were compared between groups using chi-square tests. Changes in mean scores were analyzed using linear mixed models., Results: There was no significant difference in the percentage of patients with deteriorated, stable, or improved SRCF between the treatment arms. Depending on the evaluated time point, 31% to 46% and 29% to 43% of patients in the HA-PCI and PCI arm, respectively, reported a deteriorated SRCF on the basis of the EORTC QLQ-C30 and Medical Outcomes Study. QoL outcomes were not significantly different between the study arms, except for physical functioning at 12 months ( p  = 0.019) and motor dysfunction at 24 months ( p  = 0.020)., Conclusions: Our trial did not find beneficial effects of HA-PCI over PCI on SRCF and QoL. The cognitive benefit of sparing the hippocampus in the context of PCI is still a subject of debate., (© 2023 The Authors.)

Objective: Neuropsychological literature reports varying prevalence of cognitive impairment within patient populations, despite assessment with standardized neuropsychological tests. Within the domain of oncology, the International Cognition and Cancer Task Force (ICCTF) proposed standard cutoff points to harmonize the operationalization of cognitive impairment. We evaluated how this binary classification affects agreement between two highly comparable test batteries., Method: Two hundred non-central nervous system (non-CNS) cancer patients who finished treatment (56% females; median age 53 yrs) completed traditional tests and their online equivalents in a counterbalanced design. Following ICCTF standards, impairment was defined as a score of ≥ 1.5 standard deviations ( SD s) below normative means on two tests and/or ≥ 2 SD s below normative means on one test. Agreement of classification between traditional and online assessment was evaluated using Cohen's κ. Additional Monte Carlo simulations were conducted to demonstrate how different cutoff points and test characteristics affect agreement., Results: The correlation between total scores of traditional and online assessment was .78. Proportions of impaired patients did not differ between assessment methods: 40% using traditional tests and 38% using online equivalents, χ²(1) = .17, p < .68. Nevertheless, within-person agreement in impairment classification between traditional and online assessment was merely fair ( K = .35). Monte Carlo simulations showed similarly low agreement scores ( K = .41 for 1.5 SD ; K = .33 for 2 SD criterion)., Conclusions: Our results show that binary classification can lead to a situation where two highly similar batteries fail to identify the same individuals as impaired. Additional simulations suggest that within-person agreement between assessment methods using binary classification is inherently low. Modern statistical tools may help to improve validity of impairment detection. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast cancer patients., Methods: Patients from the Tamoxifen and Exemestane Adjuvant Multinational trial received 5 years exemestane (exemestane group, n = 114) or 2.5 years tamoxifen followed by 2.5 years exemestane (sequential group, n = 92). Neuropsychological performance was assessed pre-endocrine therapy, after 1 year (ST follow-up) and at 5 years (LT follow-up). A control group of healthy participants (n = 120) were assessed with parallel intervals. With random effects modeling we evaluated cognitive changes from baseline to ST and LT follow-up. Statistical tests were 2-sided., Results: After controlling for age, intelligence quotient, attrition, menopausal symptoms, anxiety and/or depression, and/or fatigue, the sequential group showed ST and LT decline compared with control participants on verbal memory (effect size [ES] = 0.26, P = .01; ES = 0.34, P = .003) and executive function (ES = 0.27, P = .007; ES = 0.38, P = .002). Compared with the exemestane group, the sequential group demonstrated ST decline on information processing speed (ES = 0.33, P = .01) and executive function (ES = 0.32, P = .01) and LT decline on verbal memory (ES = 0.33, P = .02). The exemestane group showed no cognitive decline compared with control participants., Conclusion: Cognitive adverse effects of tamoxifen alone and after switching to exemestane were observed, suggestive of a carryover effect of tamoxifen. Our results underline the need for well-controlled, prospective trials studying cognitive effects of endocrine therapy., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally, we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline., Methods: High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test-Revised (HVLT-R)., Results: HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory., Conclusions: HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Brain metastases (BM) themselves and treatment with stereotactic radiosurgery (SRS) can influence neurocognitive functioning. This prospective study aimed to assess neurocognitive decline in patients with BM after SRS., Methods: A neuropsychological test battery was assessed yielding ten test outcomes. Neurocognitive decline at 3 and 6 months post SRS was compared to measurement prior to Gamma Knife (GK) or linear accelerator (LINAC) SRS. Reliable change indices with correction for practice effects were calculated to determine the percentage of neurocognitive decline (defined as decline on ≥ 2 test outcomes). Risk factors of neurocognitive decline were analyzed with binary logistic regression., Results: Of 194 patients pre-SRS, 40 GK and 29 LINAC patients had data accessible at 6 months. Compared to baseline, 38% of GK patients declined at 3 months, and 23% declined at 6 months. GK patients declined on attention, executive functioning, verbal memory, and fine motor skill. Of LINAC patients, 10% declined at 3 months, and 24% at 6 months. LINAC patients declined on executive functioning, verbal memory, and fine motor skills. Risk factors of neurocognitive decline at 3 months were high age, low education level and type of SRS (GK or LINAC). At 6 months, high age was a risk factor. Karnofsky Performance Scale, BM volume, number of BM, tumor progression and neurocognitive impairment pre-SRS were no risk factors., Conclusion: Neurocognitive decline occurs in a considerable proportion of patients with BM treated with GK or LINAC SRS. Overall, high age appears to be a risk factor for neurocognitive decline after SRS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Many women with breast cancer suffer from a decline in memory and executive function, particularly after treatment with chemotherapy. Recent neuroimaging studies suggest that changes in network dynamics are fundamental in decline in these cognitive functions. This has, however, not yet been investigated in breast cancer patients. Using resting state functional magnetic resonance imaging, we prospectively investigated whether changes in dynamic functional connectivity were associated with changes in memory and executive function. We examined 34 breast cancer patients that received chemotherapy, 32 patients that did not receive chemotherapy, and 35 no-cancer controls. All participants were assessed prior to treatment and six months after completion of chemotherapy, or at similar intervals for the other groups. To assess memory and executive function, we used the Hopkins Verbal Learning Test - Immediate Recall and the Trail Making Test B, respectively. Using a sliding window approach, we then evaluated dynamic functional connectivity of resting state networks supporting memory and executive function, i.e. the default mode network and frontoparietal network, respectively. Next, we directly investigated the association between cognitive performance and dynamic functional connectivity. We found no group differences in cognitive performance or connectivity measures. The association between dynamic functional connectivity of the default mode network and memory differed significantly across groups. This was not the case for the frontoparietal network and executive function. This suggests that cancer and chemotherapy alter the role of dynamic functional connectivity in memory function. Further implications of these findings are discussed., (© 2022. The Author(s).)

Background: Informing patients about chemotherapy-related cognitive symptoms (CRCS) may increase perceived cognitive symptoms. This longitudinal randomized study evaluated this Adverse Information Effect (AIE) in breast cancer patients and examined whether self-affirmation (SA) can reduce AIEs (ClinicalTrials.gov identifier: NCT04813965)., Patients and Methods: Before (neo) adjuvant chemotherapy, 160 newly diagnosed breast cancer patients were randomly allocated to receive: standard information on side-effects (control), standard information with additional information about CRCS (information), or standard and additional information with a subsequent self-affirmative text (information+SA). Online-questionnaires assessed the perceived frequency (MOS-cog) and severity (MDASI-cog) of cognitive symptoms before chemotherapy (baseline, T0), and 2.5-months (T1) and 6.5-months (T2) post-chemotherapy. Higher scores indicate less frequent, and more severe symptoms, respectively. Baseline-to-follow-up analyses using a mixed-effects modeling approach compared groups over time., Results: At T0-T2, 148, 140 and 133 patients responded, respectively (attrition rates: 8%, 5%, 5%). Frequency (ES = -0.36, P =.003) and severity (ES = 0.54, P <.001) of symptoms worsened from baseline to T1, without differences between groups. At T2, symptom frequency remained stable for informed (ES=-0.3, P =.021) and self-affirmed (ES=-0.3, P =.019) patients, but returned to baseline levels for controls. At T2, symptom severity remained increased for informed patients (ES = 0.3, P =.006), but normalized for self-affirmed patients (ES = 0.2, P =.178) and controls., Conclusion: No AIEs occurred until T2. The initial overall increase in perceived cognitive symptoms recovered at T2 for controls, but not for patients who received additional information about CRCS. Self-affirmation attenuated these longer-term AIEs for the perceived severity but not the frequency of symptoms., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

To take cancer survivorship research to the next level, it's important to gain insight in trajectories of changing patient-reported outcomes and impaired recovery after cancer. This is needed as the number of survivors is increasing and a large proportion is confronted with changing health after treatment. Mechanistic research can facilitate the development of personalized risk-stratified follow-up care and tailored interventions to promote healthy cancer survivorship. We describe how these trajectories can be studied by taking the recently extended Dutch population-based Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship (PROFILES) registry as an example. PROFILES combines longitudinal assessment of patient-reported outcomes with novel, ambulatory and objective measures (eg, activity trackers, blood draws, hair samples, online food diaries, online cognitive tests, weighing scales, online symptoms assessment), and cancer registry and pharmacy databases. Furthermore, we discuss methods to optimize the use of a multidomain data collection-like return of individual results to participants, which may improve not only patient empowerment but also long-term cohort retention. Also, advanced statistical methods are needed to handle high-dimensional longitudinal data (with missing values) and provide insight into trajectories of changing patient-reported outcomes after cancer. Our coded data can be used by academic researchers around the world. Registries like PROFILES, which go beyond boundaries of disciplines and institutions, will contribute to better predictions of who will experience changes and why. This is needed to prevent and mitigate long-term and late effects of cancer treatment and to identify new interventions to promote health., (© The Author(s) 2022. Published by Oxford University Press.)

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 ., (© 2022. The Author(s).)

Adjuvant endocrine therapy (ET) is the cornerstone of treatment for hormone-receptor positive breast cancer. Recently, ET is increasingly combined with "cyclin-dependent kinases 4 and 6'' (CDK4/6) inhibitors. Given the importance of estrogens in neural processes and the role of cyclin D in hippocampal cell proliferation, it is plausible that these therapies affect cognition, but studies on these potential cognitive effects are sparse. In this review, we summarize existing knowledge on the cognitive effects of ET and CDK4/6 inhibitors in pre-, peri- and postmenopausal patients with breast cancer. We show that several clinical studies support adverse cognitive effects, especially on verbal memory, after ET-induced decrease of estrogen-levels or inactivation of estrogen-receptors. Clinical studies on the cognitive effects of CDK4/6 inhibitors are virtually non-existent and no conclusions can yet be drawn. Longitudinal studies on the cognitive effects of the combined ET-CDK4/6 inhibitors are highly needed to properly inform patients about potential short-term and long-term cognitive side effects. These studies should preferably include cognitive assessments (including a measurement prior to ET), and be designed in such a way that they can account for variables such as type and duration of ET, CDK4/6 inhibition, menopausal status, and other disease- and treatment-related symptoms that can impact cognition, such as fatigue and distress., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The aim was to investigate the level of self-perceived cognitive functioning and its associated factors among a large population-based cohort of cancer survivors and their matched controls., Methods: Data were obtained from population-based PROFILES registry cohorts, including colon, rectum, prostate or thyroid cancer, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia, multiple myeloma (MM), melanoma, or basal cell carcinoma (BCC)/squamous cell carcinoma (SCC). All patients completed the EORTC QLQ-C30 from which self-perceived cognitive functioning, fatigue, functioning, and global health status/quality of life (GHS/QoL) were used. The PROFILES registry data were linked with the Netherlands Cancer Registry to obtain sociodemographic and clinical data., Results: Six thousand seven hundred eighty-six survivors were included (response rate=76%). Survivors, except for melanoma and BCC/SCC, reported on average lower self-perceived cognitive functioning scores compared to their matched controls (all p's<0.01). Largest differences with the norm were observed in thyroid cancer, HL, NHL and MM, and younger survivors (<50 years). Survivors with lower emotional functioning and more fatigue were more likely to report impaired self-perceived cognitive functioning., Conclusion: Self-perceived impaired cognitive functioning is prevalent among a wide range of cancer survivors, especially among survivors <50 years. Approaches targeting cognitive problems including attention for co-occurring symptoms such as fatigue and emotional impairments are needed to improve care for these patients., Implications for Cancer Survivors: Cancer survivors and clinicians should be aware that impaired self-perceived cognitive functioning is a frequently reported consequence of cancer and its treatment among survivors of various cancer types. Clinicians can redirect survivors to a relevant healthcare provider or program to target cognitive problems., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The use of Patient-Reported Outcome Measures (PROMs) for individual patient management within clinical practice is becoming increasingly important. New evidence about graphic visualization formats for PROMs scores has become available. This systematic literature review evaluated evidence for graphic visualization formats of PROMs data in clinical practice for patients and clinicians, for both individual and group level PROMs data., Methods: Studies published between 2000 and 2020 were extracted from CINAHL, PubMed, PsychInfo, and Medline. Studies included patients ≥ 18 years old in daily clinical practice. Papers not available in English, without full-text access, or that did not specifically describe visualization of PROMs data were excluded. Outcomes were: visualization preferences; interpretation accuracy; guidance for clinical interpretation., Results: Twenty-five out of 789 papers were included for final analysis. Most frequently studied formats were: bar charts, line graphs, and pie charts. Patients preferred bar charts and line graphs as these were easy and quick for retrieving information about their PROMs scores over time. Clinicians' interpretation accuracy and preferences were similar among graphic visualization formats. Scores were most often compared with patients' own previous scores; to further guide clinical interpretation, scores were compared to norm population scores. Different 'add-ons' improved interpretability for patients and clinicians, e.g. using colors, descriptions of measurement scale directionality, descriptive labels, and brief definitions., Conclusion: There was no predominant graphical visualization format approach in terms of preferences or interpretation accuracy for both patients and clinicians. Detailed clarification of graph content is essential., (© 2022. The Author(s).)

One in three people will be diagnosed with cancer during their lifetime. The community of cancer patients is growing, and several common cancers are becoming increasingly chronic; thus, cancer survivorship is an important part of health care. A large body of research indicates that cancer and cancer therapies are associated with cognitive impairment. This research has mainly concentrated on chemotherapy-associated cognitive impairment but, with the arrival of immunotherapies, the focus is expected to widen and the number of studies investigating the potential cognitive effects of these new therapies is rising. Meanwhile, patients with cognitive impairment and their healthcare providers are eagerly awaiting effective approaches to intervene against the cognitive effects of cancer treatment. In this Review, we take stock of the progress that has been made and discuss the steps that need to be taken to accelerate research into the biology underlying cognitive decline following chemotherapy and immunotherapy and to develop restorative and preventive interventions. We also provide recommendations to clinicians on how to best help patients who are currently experiencing cognitive impairment., (© 2022. Springer Nature Limited.)

Purpose: Cognitive decline is frequently observed after chemotherapy. As chemotherapy is associated with changes in brain white matter microstructure, we investigated whether white matter microstructure before chemotherapy is a risk factor for cognitive decline after chemotherapy., Methods: Neuropsychologic tests were administered before and 6 months (n = 49), 2 years (n = 32), and 3 years (n = 32) after chemotherapy in patients with breast cancer receiving anthracycline-based chemotherapy (BC + CT group), at matched intervals to patients with BC who did not receive systemic therapy (BC - CT group: n = 39, 23, and 19, respectively) and to no-cancer controls (NC group: n = 37, 29, and 28, respectively). Using multivariate normative comparison, we evaluated to what extent the cognitive profiles of patients deviated from those of controls. Fractional anisotropy (FA), derived from magnetic resonance diffusion tensor imaging, was used to measure white matter microstructure before treatment. FA was evaluated as a risk factor for cognitive decline, in addition to baseline age, fatigue, cognitive complaints, and premorbid intelligence quotient. We subsequently ran voxel-wise diffusion tensor imaging analyses to investigate white matter microstructure in specific nerve tracts., Results: Low FA independently predicted cognitive decline early (6 months, P = .013) and late (3 years, P < .001) after chemotherapy. FA did not predict cognitive decline in the BC - CT and NC groups. Voxel-wise analysis indicated involvement of white matter tracts essential for cognitive functioning., Conclusion: Low FA may reflect low white matter reserve. This may be a risk factor for cognitive decline after chemotherapy for BC. If validated in future trials, identification of patients with low white matter reserve could improve patient care, for example, by facilitating targeted, early interventions or even by influencing choices of patients and doctors for receiving chemotherapy.

Background: Impaired cognition can be a late effect after treatment in long-term testicular cancer (TC) survivors, negatively affecting their daily life. However, little data is available beyond 20 years post-treatment. We assessed cognitive impairment in very long-term TC survivors after CT or RT and compared the results with stage I TC survivors and controls., Methods: In this cross-sectional multicenter cohort study, we enrolled TC survivors (treated with orchiectomy followed by CT or RT or orchiectomy only)-with a follow-up duration ≥ 20 years-and age-matched healthy controls. Cognitive testing included the Auditory Verbal Learning Test, Letter Fluency Test, Category Fluency Test, and Trail Making Test. We used fasting blood samples to assess the presence of hypogonadism and measured cardiovascular aging parameters, including carotid pulse wave velocity (c-PWV) and advanced glycation end products (AGEs)., Results: We included 184 TC survivors (66 CT patients, 53 RT patients, and 65 orchiectomy-only patients) and 70 healthy controls. The median follow-up was 26 years (range: 20-42). TC survivors had a lower combined score of the cognitive tests (mean cumulative Z-score -0.85; 95% CI -1.39 to -0.33) compared to controls (mean 0.67; 95% CI -0.21 to 1.57, p < 0.01). In univariate analysis, the presence of hypogonadism (β -1.50, p < 0.01), high c-PWV (β -0.35, p = 0.09), and high AGEs (β -1.27, p = 0.02) were associated with lower cognitive scores, while only AGEs (β -1.17, p = 0.03) remained a significant predictor in multivariate analysis (Model R2 0.31, p < 0.01)., Conclusions: Long-term TC survivors performed worse on cognitive tests compared to controls. Physicians and patients should be informed about timely cardiovascular risk management and testosterone supplementation therapy during follow-up to reduce the risk of cognitive impairment., Trial Registration: NCT02572934.

Purpose: This longitudinal study aimed to disentangle the impact of chemotherapy on fatigue and hypothetically associated functional brain network alterations., Methods: In total, 34 breast cancer patients treated with chemotherapy (BCC +), 32 patients not treated with chemotherapy (BCC -), and 35 non-cancer controls (NC) were included. Fatigue was assessed using the EORTC QLQ-C30 fatigue subscale at two time points: baseline (T1) and six months after completion of chemotherapy or matched intervals (T2). Participants also underwent resting-state functional magnetic resonance imaging (rsfMRI). An atlas spanning 90 cortical and subcortical brain regions was used to extract time series, after which Pearson correlation coefficients were calculated to construct a brain network per participant per timepoint. Network measures of local segregation and global integration were compared between groups and timepoints and correlated with fatigue., Results: As expected, fatigue increased over time in the BCC + group (p = 0.025) leading to higher fatigue compared to NC at T2 (p = 0.023). Meanwhile, fatigue decreased from T1 to T2 in the BCC - group (p = 0.013). The BCC + group had significantly lower local efficiency than NC at T2 (p = 0.033), while a negative correlation was seen between fatigue and local efficiency across timepoints and all participants (T1 rho = - 0.274, p = 0.006; T2 rho = - 0.207, p = 0.039)., Conclusion: Although greater fatigue and lower local functional network segregation co-occur in breast cancer patients after chemotherapy, the relationship between the two generalized across participant subgroups, suggesting that local efficiency is a general neural correlate of fatigue., (© 2021. The Author(s).)

Objective: Clinical studies showing that non-central nervous system cancer patients can develop cognitive impairment have primarily focused on patients with specific cancer types and intensive treatments. To better understand the course of cognitive function in the general population of cancer patients, we assessed cognitive trajectories of patients before and after cancer diagnosis in a population-based setting., Methods: Between 1989 and 2014, 2211 participants from the population-based Rotterdam study had been diagnosed with cancer of whom 718 (32.5%) had undergone ≥1 cognitive assessment before and after diagnosis. Cognition was measured every 3 to 6 years using a neuropsychological battery. Linear mixed models were used to compare cognitive trajectories of patients before and after diagnosis with those of age-matched cancer-free controls (1:3)., Results: Median age at cancer diagnosis was 70.3 years and 47.1% were women. Most patients (68.1%) had received local treatment only. Cognitive trajectories of patients before and after cancer diagnosis were largely similar to those of controls. After diagnosis, the largest difference was found on a memory test (patients declined with 0.14 units per year on the Word Learning Test: delayed recall [95% CI = -0.35; 0.07] and controls with 0.09 units [95% CI = -0.18;-0.00], p for difference = .59)., Conclusions: In this longitudinal cohort, cancer did not appear to alter the trajectory of change in cognitive test results over time from that seen in similar individuals without cancer, although most cancer patients did not receive systemic therapies. Future studies should focus on identifying subgroups of patients who are at high risk for developing cognitive impairment., (© 2021 John Wiley & Sons Ltd.)

Objective: Since computerized cognitive test performance may be influenced by computer experience, correction for this measure might be needed. This study examined how to correct for computer experience by examining its influence on online and traditional tests. Method: 248 healthy adults completed an online neuropsychological test battery and 70 adults completed traditional equivalents of the tests. Computer experience was assessed by a performance-based and a self-report measure. Regression analyses were applied to examine their influence on the online and traditional tests. Results: After correction for demographics, the performance-based measure was associated with online and traditional, predominantly speed-based, tests. The self-report measure was also associated with speed-based online tests but not with most traditional tests. Conclusions: Correcting computerized neuropsychological tests using a performance-based measure of computer experience would be unwise, because this measure also seems to tap into cognitive functions. A correction using a self-report measure might be better and is appropriate.