Can metaphors help us better remember wines? The effect of wine evaluation style on short-term recognition of red wines.

People are generally poor at remembering complex food stimuli, such as wine. While writing a description has been shown to improve memory performance, talking about wine is generally a difficult task for novices. However, giving novices a framework in which to evaluate the wine may help with the memory process. Using a short-term recognition task, this experiment compared different forms of wine evaluation on the to-be-remembered wine sample, using either 1) a classic smell and taste evaluation, 2) a multisensory metaphor selection task with visual, auditory, and tactile metaphors, or 3) a control condition with no writing. Results from 153 participants revealed that recognition performance between the three groups was not significantly different. Secondary analysis revealed that recognition accuracy was correlated with wine liking for the control group, suggesting that in the absence of explicitly evaluating the wine, participants relied on wine liking as a cue for memory. Implications for theory development and applications in wine education are discussed.

Biological and psychological predictors of cognitive function in breast cancer patients before surgery.

PURPOSE: Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. METHODS: 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. RESULTS: Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p < .001) than HC. BC patients and HC did not differ in overall cognitive impairment (p = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. CONCLUSION: Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. CLINICAL TRIALS REGISTRATION NUMBER: NCT04418856, date of registration: 06.05.2020.

Psychological and behavioral symptoms in patients with melanoma: A systematic review and meta-analysis.

OBJECTIVE: Improved survival rates have made it increasingly important for clinicians to focus on cancer survivorship issues affecting the quality of life of melanoma patients. To provide a comprehensive overview of the disease and treatment-related issues affecting such patients, we conducted a systematic review and meta-analysis of the literature to estimate the prevalence of symptoms of depression, anxiety, fatigue, sleep disturbance, and cognitive problems among melanoma patients, both uveal and cutaneous, before, during and after treatment. METHODS: The review was preregistered with PROSPERO (#CRD42020189847) and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of the literature published up until June 2022 was undertaken using PubMed, PsycInfo, the Cochrane Library, and CINAHL. Two independent reviewers screened 1418 records and quality-rated included studies. The reported prevalence rates of symptoms were pooled using a random-effects model. RESULTS: Sixty-six studies including a total of 12,400 melanoma patients published between 1992 and 2022 were included. Pooled prevalence rates ranged from 6% to 16% for depression and 7%-30% for anxiety across diagnoses (uveal and cutaneous melanoma) and assessment time points. One third of the patients (35%) reported clinically significant fatigue, 20%-44% had cognitive complaints, while prevalence of sleep disturbance was not reported. Quality assessment indicated that 80% of the studies were of good quality. CONCLUSION: A large body of research shows that depression and anxiety symptoms are prevalent in melanoma patients before, during and after treatment. However, research examining other symptoms known to affect quality of life, such as fatigue, sleep disturbances, and cognitive problems, is still needed.

The importance of sleep in memory, learning, and other cognitive functions.

Sleep is important for brain health, having both a restorative function and playing an important role in cognitive functions, e.g., attention, memory, learning, and planning. This review finds that sleep disturbances are prevalent and associated with poorer cognitive functioning in neurodegenerative disorders such as Parkinson's disease and in people with non-neurodegenerative diseases such as cancer and mood disorders. Screening for and treating sleep disturbances are potential supplementary approaches to preventing and treating cognitive impairment.

Quality of life of adolescent and adult survivors of childhood cancer in Europe-A systematic review.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.

Measuring Cognitive Abilities in the Wild: Validating a Population-Scale Game-Based Cognitive Assessment.

Rapid individual cognitive phenotyping holds the potential to revolutionize domains as wide-ranging as personalized learning, employment practices, and precision psychiatry. Going beyond limitations imposed by traditional lab-based experiments, new efforts have been underway toward greater ecological validity and participant diversity to capture the full range of individual differences in cognitive abilities and behaviors across the general population. Building on this, we developed Skill Lab, a novel game-based tool that simultaneously assesses a broad suite of cognitive abilities while providing an engaging narrative. Skill Lab consists of six mini-games as well as 14 established cognitive ability tasks. Using a popular citizen science platform (N = 10,725), we conducted a comprehensive validation in the wild of a game-based cognitive assessment suite. Based on the game and validation task data, we constructed reliable models to simultaneously predict eight cognitive abilities based on the users' in-game behavior. Follow-up validation tests revealed that the models can discriminate nuances contained within each separate cognitive ability as well as capture a shared main factor of generalized cognitive ability. Our game-based measures are five times faster to complete than the equivalent task-based measures and replicate previous findings on the decline of certain cognitive abilities with age in our large cross-sectional population sample (N = 6369). Taken together, our results demonstrate the feasibility of rapid in-the-wild systematic assessment of cognitive abilities as a promising first step toward population-scale benchmarking and individualized mental health diagnostics.

The effect of air quality on sleep and cognitive performance in school children aged 10-12 years: a double-blinded, placebo-controlled, crossover trial.

OBJECTIVES: To investigate the effect of CO2 during sleep on next-morning cognitive performance in young schoolchildren, the authors performed a double-blind fully balanced crossover placebo-controlled study. MATERIAL AND METHODS: The authors included 36 children aged 10-12 years in the climate chamber. The children slept at 21°C in 6 groups each at 3 different conditions separated by 7 days in a random order. Conditions were as follows: high ventilation with CO2 at 700 ppm, high ventilation with added pure CO2 at 2000-3000 ppm, and reduced ventilation with CO2 at 2-3000 ppm and bioeffluents. Children were subjected to a digital cognitive test battery (CANTAB) in the evening prior to sleep and on the next morning after breakfast. Sleep quality was monitored with wrist actigraphs. RESULTS: There were no significant exposure effects on cognitive performance. Sleep efficiency was significantly lower at high ventilation with CO2 at 700 ppm which is considered to be a chance effect. No other effects were seen, and no relation between air quality during sleep and next-morning cognitive performance was observed in the children emitting an estimated 10 lCO2/h per child. CONCLUSIONS: No effect of CO2 during sleep was found on next day cognition. The children were awakened in the morning, and spent from 45-70 min in well-ventilated rooms before they were tested. Hence, it cannot be precluded that the children have benefitted from the good indoor air quality conditions before and during the testing period. The slightly better sleep efficiency during high CO2 concentrations might be a chance finding. Hence, replication is needed in actual bedrooms controlling for other external factors before any generalizations can be made. Int J Occup Med Environ Health. 2023;36(2):177-91.

Neurocognitive function and health-related quality of life in a nationwide cohort of long-term childhood brain tumor survivors.

Background: Childhood brain tumor survivors are at high risk of late effects, especially neurocognitive impairment. Limited data are available examining neurocognitive function and associations with quality of life (QoL) in childhood brain tumor survivors. Our aim was to examine neurocognitive function in childhood brain tumor survivors, and associations with QoL and symptom burden. Methods: Five-year survivors of brain tumors over the age of 15 were identified in the Danish Childhood Cancer Registry (n = 423). Eligible and consenting participants completed neuropsychological tests and questionnaires assessing QoL, insomnia, fatigue, anxiety, and depression. Survivors treated with radiation (n = 59) were statistically compared with survivors not treated with radiation (n = 102). Results: In total, 170 survivors participated (40.2% participation rate). Sixty-six percent of the survivors who completed neurocognitive tests (n = 161) exhibited overall neurocognitive impairment. Survivors treated with radiation, especially whole-brain irradiation, exhibited poorer neurocognitive outcomes than survivors not treated with radiation. Neurocognitive outcomes for survivors treated with surgery were below normative expectations. Furthermore, a number of survivors experienced significant fatigue (40%), anxiety (23%), insomnia (13%), and/or depression (6%). Survivors treated with radiation reported lower quality of life (QoL) and higher symptom burden scores than survivors not treated with radiation; particularly in physical functioning, and social functioning with symptoms of fatigue. Neurocognitive impairment was not associated with QoL or symptom burden. Conclusions: In this study, a majority of the childhood brain tumor survivors experienced neurocognitive impairment, reduced QoL, and high symptom burden. Although not associated with each other, it is apparent that childhood brain tumor survivors experience not only neurocognitive dysfunction but may also experience QoL impairments and significant symptom burden.

Circadian disruption and cancer- and treatment-related symptoms.

Cancer patients experience a number of co-occurring side- and late-effects due to cancer and its treatment including fatigue, sleep difficulties, depressive symptoms, and cognitive impairment. These symptoms can impair quality of life and may persist long after treatment completion. Furthermore, they may exacerbate each other's intensity and development over time. The co-occurrence and interdependent nature of these symptoms suggests a possible shared underlying mechanism. Thus far, hypothesized mechanisms that have been purported to underlie these symptoms include disruptions to the immune and endocrine systems. Recently circadian rhythm disruption has emerged as a related pathophysiological mechanism underlying cancer- and cancer-treatment related symptoms. Circadian rhythms are endogenous biobehavioral cycles lasting approximately 24 hours in humans and generated by the circadian master clock - the hypothalamic suprachiasmatic nucleus. The suprachiasmatic nucleus orchestrates rhythmicity in a wide range of bodily functions including hormone levels, body temperature, immune response, and rest-activity behaviors. In this review, we describe four common approaches to the measurement of circadian rhythms, highlight key research findings on the presence of circadian disruption in cancer patients, and provide a review of the literature on associations between circadian rhythm disruption and cancer- and treatment-related symptoms. Implications for future research and interventions will be discussed.

Cancer-related cognitive impairment in non-CNS cancer patients: Targeted review and future action plans in Europe.

Cancer-related cognitive impairment (CRCI) has increasingly been identified over the last two decades in non-CNS system cancer patients. Across Europe, researchers have contributed to this effort by developing preclinical models, exploring underlying mechanisms and assessing cognitive and quality of life changes. The ultimate goal is to develop interventions to treat patients experiencing CRCI. To do so, new challenges need to be addressed requiring the implementation of multidisciplinary research groups. In this consensus paper, we summarize the state of the art in the field of CRCI combined with the future challenges and action plans in Europe. These challenges include data sharing/pooling, standardization of assessments as well as assessing additional biomarkers and neuroimaging investigations, notably through translational studies. We conclude this position paper with specific actions for Europe based on shared scientific expert opinion and stakeholders involved in the Innovative Partnership for Action Against Cancer, with a particular focus on cognitive intervention programs.

Examining the Efficacy of Bright Light Therapy on Cognitive Function in Hematopoietic Stem Cell Transplant Survivors.

Patients who have undergone hematopoietic stem cell transplant (HSCT) may experience cognitive impairment that can persist after treatment. Several studies have shown that bright light therapy may improve cognition, potentially due to its effects on the circadian system via brain regions that respond preferentially to light. In this double-blind randomized controlled trial, the efficacy of bright light therapy on cognition was examined in HSCT survivors. Forty-seven HSCT survivors at an urban hospital in the United States were screened for mild cognitive impairment, randomized to either bright white light (BWL) or comparison dim red light (DRL) conditions using a block randomization approach, and instructed to use their assigned light box every morning upon awakening for 30 min for 4 weeks. Assessments occurred at baseline, the end of the second week of the intervention, the end of the intervention, and at follow-up (8 weeks later). The primary outcome was objective cognitive function as measured by a global composite score on neuropsychological tests. Secondary outcomes included cognitive performance in individual domains, self-reported cognitive function, fatigue, sleep and sleep quality, and circadian rhythm robustness. Repeated-measures linear mixed models for both objective and self-reported cognitive function indicated significant main effects for time (ps < 0.05) suggesting significant improvements in both conditions over time. Time by light condition interaction effects were not significant. Models focused on secondary outcomes yielded no significant effects. Both BWL and DRL groups demonstrated significant improvements in objective cognitive and self-reported cognitive function over time, but there was no hypothesized effect of BWL over DRL nor associations with circadian rhythm robustness. Therapeutic effects of both light conditions, practice effects, and/or placebo effects may account for the findings.Trial registration: ClinicalTrials.gov Identifier: NCT02677987 (9 February 2016).

Sleep and allostatic load: A systematic review and meta-analysis.

The detrimental effects of sleep disturbances on health and wellbeing are well-established but not fully understood. The allostatic load model has been suggested as a framework for understanding the adverse effects of sleep disturbances. We conducted a systematic review and meta-analysis to examine the associations of sleep disturbance and sleep duration with allostatic load. PubMed, PsycINFO, Embase, and Web of Science were searched for records relating to sleep and allostatic load published from 1993 to January 14th, 2022. Two independent raters screened 395 titles and abstracts and 51 full texts. Data were extracted from 18 studies that were assessed for methodological quality. Of these, 17 studies of 26,924 participants were included in the meta-analysis. Sleep disturbance was significantly associated with higher allostatic load (effect size correlation [ESr] = 0.09, p < 0.001), and the association was weaker in samples with a larger proportion of women. When compared to normal sleep, long sleep was significantly associated with higher allostatic load (ESr = 0.12, p = 0.003). Results indicated heterogeneity. No association was found for short sleep (ESr = 0.05, p = 0.069) or sleep duration (ESr = -0.06, p = 0.36). Future research should identify mechanisms and directionality in longitudinal studies.

Changes in sleep following internet-delivered cognitive-behavioral therapy for insomnia in women treated for breast cancer: A 3-year follow-up assessment.

BACKGROUND: Sleep disturbances are common in women treated for breast cancer. We have previously shown that internet-delivered cognitive-behavioral therapy for insomnia (e-CBT-I) is an efficacious, low-cost treatment approach. Furthermore, research has shown that e-CBT-I can result in sustained improvements at 12 months post-treatment. However, given the complexity and long duration of post-treatment symptomatology in breast cancer patients, as well as the recommended use of antihormonal therapy for up to 10 years, it is relevant to investigate long-term (>12 months) changes in sleep following e-CBT-I in this population. In the present study, we report data from a 3-year long-term follow-up assessment after e-CBT-I. METHODS: Women treated for breast cancer with sleep disturbances (Pittsburg Sleep Quality Index [PSQI] global score >5) who had previously been enrolled in a randomized-controlled trial investigating the efficacy of e-CBT-I (n = 255), were invited to participate in a 3-year follow-up study. All women in the initial control group had also been granted access to e-CBT-I. Assessment included self-reported sleep quality (PSQI), insomnia severity (Insomnia Severity Index, ISI), cancer-related fatigue and symptoms of depression. Within-group changes in these outcomes from baseline to the 3-year long-term follow-up assessment were analyzed. RESULTS: A total of 131 women (51%) participated in the 3-year follow-up study of which 77 (59%) were from the initial intervention group and 54 (41%) from the initial control group. For the pooled sample, within-group improvements from baseline to the 3-year follow-up assessment corresponding to large effect sizes were observed in sleep quality (Cohen's d = 1.0 95% CI [0.78, 1.21]) and insomnia severity (Cohen's d = 1.36 CI 95% [1.12, 1.59]). Similar changes were observed in cancer-related fatigue (Cohen's d = 0.48 CI 95% [0.30, 0.66]) and symptoms of depression (Cohen's d = 0.80 CI 95%. [0.60, 0.99]). The proportion of patients with scores above established cut-offs on the PSQI and the ISI were 56.1% and 29.8%, respectively. Within the initial intervention group, 15.6% evidenced relapse at the 3-year assessment. CONCLUSION: Overall, these results indicate that long-term sleep quality and insomnia severity following the use of e-CBT-in women treated for breast cancer is significantly lower than the pre-treatment levels. However, a substantial proportion of participants still evidence sleep disturbances.

Sleep During Oncological Treatment - A Systematic Review and Meta-Analysis of Associations With Treatment Response, Time to Progression and Survival.

Introduction: Disrupted sleep and sleep-wake activity are frequently observed in cancer patients undergoing oncological treatment. These disruptions are often associated with aggravated symptom burden and diminished health-related quality of life that in turn may compromise treatment adherence and, thus, effectiveness. In addition, disrupted sleep has been linked to carcinogenic processes, which ultimately could result in worse prognostic outcomes. Aims: Our aim was to systematically review and conduct a meta-analysis of studies examining the associations between sleep and sleep-wake activity and prognostic outcomes in cancer patients undergoing oncological treatment. Methods: A comprehensive systematic search of English language papers was undertaken in June 2020 using PubMed, The Cochrane Library, and CINAHL. Two reviewers independently screened 4,879 abstracts. A total of 26 papers were included in the narrative review. Thirteen papers reporting hazard ratios reflecting associations between a dichotomized predictor variable (sleep) and prognostic outcomes were subjected to meta-analysis. Results: Nineteen of the 26 eligible studies on a total of 7,092 cancer patients reported associations between poorer sleep and poorer response to treatment, shorter time to progression, and/or reduced overall survival, but were highly heterogeneous with respect to the sleep and outcome parameters investigated. Meta-analysis revealed statistically significant associations between poor self-reported sleep and reduced overall survival (HR = 1.33 [95% CI 1.09-1.62], k = 11), and shorter time to progression (HR = 1.40 [95% CI 1.23-1.59], k = 3) and between poor objectively assessed sleep and reduced overall survival (HR = 1.74 [95% CI 1.05-2.88], k = 4). Conclusion: The current findings indicate that disturbed sleep during treatment may be a relevant behavioral marker of poor cancer prognosis. The limited number of studies, the common use of single item sleep measures, and potential publication bias highlight the need for further high quality and longitudinal studies.

Systematic Review: Sleep Disorders Based on Objective Data in Children and Adolescents Treated for a Brain Tumor.

Background: Tumors of the central nervous system (CNS) are the most common solid childhood malignancy. Over the last decades, treatment developments have strongly contributed to the improved overall 5-year survival rate, which is now approaching 75%. However, children now face significant long-term morbidity with late-effects including sleep disorders that may have detrimental impact on everyday functioning and quality of life. The aims of this study were to (1) describe the symptoms that lead to polysomnographic evaluation; (2) describe the nature of sleep disorders diagnosed in survivors of childhood CNS tumor using polysomnography (PSG); and (3) explore the association between tumor location and diagnosed sleep disorder. Methods: An extensive literature search following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA) was conducted. Inclusion criteria were children and adolescents diagnosed with a CNS tumor age <20 years having a PSG performed after end of tumor treatment. The primary outcome was sleep disorder confirmed by PSG. Results: Of the 1,658 studies identified, 11 met the inclusion criteria. All the included articles were appraised for quality and included in the analysis. Analyses indicated that sleep disorders commonly occur among childhood CNS tumor survivors. Symptoms prior to referral for PSG were excessive daytime sleepiness (EDS), fatigue, irregular breathing during sleep and snoring. The most common sleep disorders diagnosed were sleep-related breathing disorders (i.e., obstructive sleep apnea) and central disorders of hypersomnolence (i.e., narcolepsy). Conclusion: Our findings point to the potential benefit of systematically registering sleep disorder symptoms among CNS tumor patients together with tumor type and treatment information, so that at-risk patients can be identified early. Moreover, future rigorous and larger scale controlled observational studies that include possible modifiable confounders of sleep disorders such as fatigue and obesity are warranted. Clinical Trial Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021243866, identifier [CRD42021243866].

Cognitive impairment and associations with structural brain networks, endocrine status, and risk genotypes in newly orchiectomized testicular cancer patients.

A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the underlying pathophysiology. The present study assessed CI in newly orchiectomized TCPs and explored the structural brain networks, endocrine status, and selected genotypes. Forty TCPs and 22 healthy controls (HCs) underwent neuropsychological testing and magnetic resonance imaging, and provided a blood sample. CI was defined as a z-score ≤ -2 on one neuropsychological test or ≤ -1.5 on two neuropsychological tests, and structural brain networks were investigated using graph theory. Associations of cognitive performance with brain networks, endocrine status (including testosterone levels and androgen receptor CAG repeat length), and genotypes (APOE, BDNF, COMT) were explored. Compared with HCs, TCPs performed poorer on 6 out of 15 neuropsychological tests, of which three tests remained statistically significant when adjusted for relevant between-group differences (p < 0.05). TCPs also demonstrated more CI than HCs (65% vs. 36%; p = 0.04). While global brain network analysis revealed no between-group differences, regional analysis indicated differences in node degree and betweenness centrality in several regions (p < 0.05), which was inconsistently associated with cognitive performance. In TCPs, CAG repeat length was positively correlated with delayed memory performance (r = 0.36; p = 0.02). A COMT group × genotype interaction effect was found for overall cognitive performance in TCPs, with risk carriers performing worse (p = 0.01). No effects were found for APOE, BDNF, or testosterone levels. In conclusion, our results support previous findings of a high incidence of CI in newly orchiectomized TCPs and provide novel insights into possible mechanisms.

Androgen deprivation therapy and cognitive decline-associations with brain connectomes, endocrine status, and risk genotypes.

BACKGROUND: Evidence suggests that prostate cancer (PC) patients undergoing androgen deprivation therapy (ADT) are at risk for cognitive decline (CD), but the underlying mechanisms are less clear. In the present study, changes in cognitive performance and structural brain connectomes in PC patients undergoing ADT were assessed, and associations of cognitive changes with endocrine status and risk genotypes were explored. METHODS: Thirty-seven PC patients underwent cognitive assessment, structural MRI, and provided blood samples prior to ADT and after 6 months of treatment. Twenty-seven age- and education-matched healthy controls (HCs) underwent the same assessments. CD was determined using a standardized regression-based approach and defined as z-scores ≤ -1.64. Changes in brain connectomes were evaluated using graph theory. Associations of CD with testosterone levels and genotypes (APOE, COMT, BDNF) were explored. RESULTS: Compared with HCs, PC patients demonstrated reduced testosterone levels (p < 0.01) and higher rates of decline for 13 out of 15 cognitive outcomes, with three outcomes related to two cognitive domains, i.e., verbal memory and visuospatial learning and memory, reaching statistical significance (p ≤ 0.01-0.04). Testosterone level changes did not predict CD. COMT Met homozygote PC patients evidenced larger reductions in visuospatial memory compared with Val carriers (p = 0.02). No between-group differences were observed in brain connectomes across time, and no effects were found of APOE and BDNF. CONCLUSIONS: Our results indicate that PC patients undergoing ADT may evidence CD, and that COMT Met homozygotes may be at increased risk of CD. The results did not reveal changes in brain connectomes or testosterone levels as underlying mechanisms. More research evaluating the role of ADT-related disruption of the dynamics of the hypothalamic-pituitary-gonadal axis is needed.

Cognitive changes and brain connectomes, endocrine status, and risk genotypes in testicular cancer patients-A prospective controlled study.

OBJECTIVE: Previous research has indicated cognitive decline (CD) among testicular cancer patients (TCPs), even in the absence of chemotherapy, but little is known about the underlying pathophysiology. The present study assessed changes in cognitive functions and structural brain connectomes in TCPs and explored the associations between cognitive changes and endocrine status and hypothesized risk genotypes. METHODS: Thirty-eight newly orchiectomized TCPs and 21 healthy controls (HCs) comparable to TCPs in terms of age and years of education underwent neuropsychological testing, structural MRI, and a biological assessment at baseline and 6 months later. Cognitive change was assessed with a neuropsychological test battery and determined using a standardized regression-based approach, with substantial change defined as z-scores ≤-1.64 or ≥1.64. MRI scans and graph theory were used to evaluate changes in structural brain connectomes. The associations of cognitive changes with testosterone levels, androgen receptor gene (AR) CAG repeat length, and genotypes (APOE, COMT, and BDNF) were explored. RESULTS: Compared with HCs, TCPs showed higher rates of substantial decline on processing speed and visuospatial ability and higher rates of substantial improvement on verbal recall and visuospatial learning (p < 0.05; OR = 8.15-15.84). Brain network analysis indicated bilateral thalamic changes in node degree in HCs, but not in TCPs (p < 0.01). In TCPs, higher baseline testosterone levels predicted decline in verbal memory (p < 0.05). No effects were found for AR CAG repeat length, APOE, COMT, or BDNF. CONCLUSIONS: The present study confirms previous findings of domain-specific CD in TCPs following orchiectomy, but also points to domain-specific improvements. The results do not indicate changes in brain connectomes or endocrine status to be the main drivers of CD. Further studies evaluating the mechanisms underlying CD in TCPs, including the possible role of the dynamics of the hypothalamic-pituitary-gonadal axis, are warranted.