Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on cognition in women with high familial risk of ovarian cancer: A cross-sectional study.

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.

Subgroups of cognitively affected and unaffected breast cancer survivors after chemotherapy: a data-driven approach.

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.

Effects of tamoxifen and exemestane on cognitive function in postmenopausal patients with breast cancer.

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.

Standardized item selection for alternate computerized versions of Rey Auditory Verbal Learning Test(-based) word lists.

INTRODUCTION: Despite an increasing need for new Rey Auditory Verbal Learning Test (RAVLT)-based word lists in computerized testing, no criteria or standardized procedures exist for its development. To lay a foundation for future development of new and alternate computerized RAVLT(-based) word lists, we present cross-lingual word criteria, developed new lists using the criteria and evaluated performance on the lists using online assessment. METHOD: Based on psycholinguistic literature, we identified relevant word selection criteria. To validate the criteria, we developed two new American-English word lists and one new Dutch list, and administered the RAVLT using visual presentation of the new or original list in an online American (n = 248) and Dutch sample (n = 246) of healthy people. We compared performance of the new and original word lists on trial scores and serial position effects using Bayesian correlations and analyses of variance. Additionally, we compared proportions of correct responses per item, corrected for serial position. RESULTS: We identified 13 relevant word selection criteria. The criteria led to two new highly comparable American-English word lists with lower trial scores compared to the original American-English list, indicating that the criteria helped to develop parallel lists with fewer associations between items. The new Dutch word list showed similar trial scores, serial position effects, and proportions of correct responses per item corrected for serial position compared to the original Dutch version. CONCLUSIONS: The systematic use of word selection criteria can facilitate development of new parallel word lists, including in new language areas. Future studies should evaluate the use of the word criteria for the other sections of the RAVLT (such as delayed recall and recognition), performance using original test modalities (auditory presentation and recall of words) as well as performance in clinical samples.

How to Correct for Computer Experience in Online Cognitive Testing?

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.

Computational Modeling of Neuropsychological Test Performance to Disentangle Impaired Cognitive Processes in Cancer Patients.

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.

Assessing cognition and daily function in early dementia using the cognitive-functional composite: findings from the Catch-Cog study cohort.

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 (ß = .61, p < .001), poorer quality of life (ß = .51, p < .001), higher caregiver burden (ß = - .51, p < .001), more apathy (ß = - .36, p < .001), and less cortical volume (ß = .34, p = .02). Whilst correlations between the CFC and traditional measures were moderate to strong (ranging from - .65 to .83, all p < .001), histograms showed floor and ceiling effects for the traditional tests as compared to the CFC. CONCLUSIONS: Our findings illustrate that the CFC has good construct validity, captures clinically relevant aspects of disease severity, and shows no range restrictions in scoring. It therefore provides a more useful outcome measure than traditional tests to evaluate cognition and function in MCI and mild AD.

A novel cognitive-functional composite measure to detect changes in early Alzheimer's disease: Test-retest reliability and feasibility.

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.