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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.

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.

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.

There is a need to better identify impaired cognitive processes to increase our understanding of cognitive dysfunction caused by cancer and cancer treatment and to improve interventions. The Trail Making Test is frequently used for evaluating information-processing speed (part A) and executive function (part B), but interpretation of its outcomes is challenging because performance depends on many cognitive processes. To disentangle processes, we collected high-resolution data from 192 non–central nervous system cancer patients who received systemic therapy and 192 cancer-free control participants and fitted a Shifted-Wald computational model. Results show that cancer patients were more cautious than controls (Cohen d = 0.16). Patients were cognitively slower than controls when the task required task switching (Cohen d = 0.16). Our results support the idea that cancer and cancer treatment accelerate cognitive aging. Our approach allows more precise assessment of cognitive dysfunction in cancer patients and can be extended to other instruments and patient populations.

Background: A subset of patients with breast cancer is vulnerable to treatment-related cognitive problems. However, relatively little is known about the cognitive effects of endocrine treatment and the novel cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the metastatic setting. Research on possible cognitive effects of these therapies is needed, since cognitive impairment can affect role functioning, independence and quality of life. Trial design: The current study is a side study of the SONIA (Selecting the optimal position of CDK4/6 inhibitors in hormone-receptor-positive advanced breast cancer) trial: a multicenter, randomized phase III study. The side study is an observational study with nine months of follow-up, comparing two intervention groups (first line non-steroidal aromatase inhibitor + CDK4/6 inhibition vs. single agent non-steroidal aromatase inhibitor) and a reference group of people without a history of cancer. Cognition will be measured at start of treatment (T0) and nine months later (T1), using the Amsterdam Cognition Scan, a validated online neuropsychological test battery that is completed at home without supervision. It includes tests of among others attention, memory, and executive functioning, and two questionnaires on anxiety and depression, and fatigue. Specific aims: The main objective is to evaluate if there is a difference in cognitive functioning over time in patients with metastatic breast cancer who will undergo first line endocrine treatment + CDK4/6 inhibition vs. endocrine treatment alone. Eligibility criteria: All patients who participate in the main SONIA study will be eligible for participation: adult women (≥ 18 years of age) with proven diagnosis of hormone receptor-positive, human epidermal growth factor receptor 2 negative adenocarcinoma of the breast with evidence of loco-regional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent, for whom chemotherapy is not clinically indicated and who have not received any prior systemic anti-cancer therapy for metastatic disease. Participants in the reference group are patients’ female relatives/friends without a history of cancer and without neurological/psychiatric symptoms influencing cognition, who have a sufficient level of Dutch and access to a computer with internet. Statistical methods: We will use a mixed effects modeling approach to examine changes in cognition from baseline to follow-up between the two intervention groups and the reference group, adjusting for non-ignorable drop-out patterns. The primary endpoint will be the change from baseline to follow-up on the total score of cognition. Present accrual and target accrual: With an accrual period of 21 months and 9 months of follow-up, inclusion of 260 patients is required. In addition, our already existing reference group (n=157) will be expanded by recruiting participants’ female relatives/friends without a history of cancer. As of June 2019, 435 patients have enrolled in the main SONIA study. Target accrual is 1050 patients. Contact information Study coordinator: Philippe Lee Meeuw Kjoe, Netherlands Cancer Institute, p.lee.meeuw.kjoe@nki.nl PI: Elsken van der Wall, MD, PhD, UMC Utrecht Cancer Center, E.vanderWall@umcutrecht.nl PI: Sanne Schagen, PhD, Netherlands Cancer Institute, s.schagen@nki.nl Citation Format: Philippe Lee Meeuw Kjoe, Elsken van der Wall, Inge Konings, Agnes Jager, Gabe Sonke, Annemiek van Ommen-Nijhof, Sanne Schagen. Evaluation of cognitive functioning in patients with metastatic breast cancer treated with endocrine or combined therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-04-06.

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.

Background The cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population. Methods Baseline data of the Capturing Changes in Cognition study was used: an international, prospective cohort study including participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD) dementia, and dementia with Lewy bodies (DLB). The CFC comprises seven existing cognitive tests focusing on memory and executive functions (EF) and the informant-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). Construct validity and clinical relevance were assessed by (1) confirmatory factor analyses (CFA) using all CFC subtests and (2) linear regression analyses relating the CFC score (independent) to reference measures of disease severity (dependent), correcting for age, sex, and education. To assess the suitability for the target population, we compared score distributions of the CFC to those of traditional tests (Alzheimer’s Disease Assessment Scale–Cognitive subscale, Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale, and Clinical Dementia Rating scale). Results A total of 184 participants were included (age 71.8 ± 8.4; 42% female; n = 14 SCD, n = 80 MCI, n = 78 AD, and n = 12 DLB). CFA showed that the hypothesized three-factor model (memory, EF, and IADL) had adequate fit (CFI = .931, RMSEA = .091, SRMR = .06). Moreover, worse CFC performance was associated with more cognitive decline as reported by the informant (β = .61, p

Introduction To improve the detection of changes in Alzheimer's disease (AD), we designed the cognitive-functional composite (CFC). As a first validation step, we investigated its test–retest reliability and feasibility of use. Methods We performed a test–retest study with 2–3 weeks between assessments, including patients with mild cognitive impairment (MCI) or mild AD dementia and cognitively healthy participants. We calculated intraclass correlation coefficients (ICCs) type absolute agreement for all CFC measures and compared baseline and retest scores using paired-samples t-tests. We evaluated feasibility by interviewing participants. Results Forty-three patients (40% female, mean age = 69.9) and 30 controls (50% female, mean age = 65) were included. Subtest intraclass correlation coefficients ranged from .70 to .96. We found negligible improvements after retesting on only two subtests. Overall, patients perceived the administration of the CFC as feasible. Discussion The CFC is a stable and feasible measure in MCI and mild AD dementia, and thereby meets important quality metrics for clinically meaningful outcome measures., Highlights • We investigated stability and feasibility of the cognitive-functional composite (CFC). • We demonstrated good test–retest reliability for all CFC subtests. • We only found negligible practice effects on two CFC subtests. • Overall, patients experienced the administration of the CFC as feasible.