Cancer patients may experience a decrease in cognitive functioning before, during and after cancer treatment. So far, the Quality of Life Group of the European Organisation for Research and Treatment ...of Cancer (EORTC QLG) developed an item bank to assess self-reported memory and attention within a single, cognitive functioning scale (CF) using computerized adaptive testing (EORTC CAT Core CF item bank). However, the distinction between different cognitive functions might be important to assess the patients' functional status appropriately and to determine treatment impact. To allow for such assessment, the aim of this study was to develop and psychometrically evaluate separate item banks for memory and attention based on the EORTC CAT Core CF item bank. In a multistep process including an expert-based content analysis, we assigned 44 items from the EORTC CAT Core CF item bank to the memory or attention domain. Then, we conducted psychometric analyses based on a sample used within the development of the EORTC CAT Core CF item bank. The sample consisted of 1030 cancer patients from Denmark, France, Poland, and the United Kingdom. We evaluated measurement properties of the newly developed item banks using confirmatory factor analysis (CFA) and item response theory model calibration. Item assignment resulted in 31 memory and 13 attention items. Conducted CFAs suggested good fit to a 1-factor model for each domain and no violations of monotonicity or indications of differential item functioning. Evaluation of CATs for both memory and attention confirmed well-functioning item banks with increased power/reduced sample size requirements (for CATs greater than or equal to 4 items and up to 40% reduction in sample size requirements in comparison to non-CAT format). Two well-functioning and psychometrically robust item banks for memory and attention were formed from the existing EORTC CAT Core CF item bank. These findings could support further research on self-reported cognitive functioning in cancer patients in clinical trials as well as for real-word-evidence. A more precise assessment of attention and memory deficits in cancer patients will strengthen the evidence on the effects of cancer treatment for different cancer entities, and therefore contribute to shared and informed clinical decision-making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study applies multimodal MRI to investigate neurodevelopment in nine-year-old children born to cancer-complicated pregnancies.
In this cohort study, children born after cancer-complicated ...pregnancies were recruited alongside 1:1 matched controls regarding age, sex and gestational age at birth (GA). Multimodal MRI was used to investigate whole-brain and subcortical volume, cortical structure (using surface-based morphometry), white matter microstructure (using fixel-based analysis) and functional connectivity (using resting-state blood-oxygen-level-dependant signal correlations). Graph theory probed whole-brain structural and functional organization. For each imaging outcome we conducted two group comparisons: 1) children born after cancer-complicated pregnancies versus matched controls, and 2) the subgroup of children with prenatal chemotherapy exposure versus matched controls. In both models, we used the covariate of GA and the group-by-GA interaction, using false-discovery-rate (FDR) or family-wise-error (FWE) correction for multiple comparisons. Exploratory post-hoc analyses investigated the relation between brain structure/function, neuropsychological outcome and maternal oncological/obstetrical history.
Forty-two children born after cancer-complicated pregnancies were included in this study, with 30 prenatally exposed to chemotherapy. Brain organization and functional connectivity were not significantly different between groups. Both cancer and chemotherapy in pregnancy, as compared to matched controls, were associated with a lower travel depth, indicating less pronounced gyrification, in the left superior temporal gyrus (pFDR ≤ 006), with post-hoc analysis indicating platinum derivatives during pregnancy as a potential risk factor (p = .028). Both cancer and chemotherapy in pregnancy were related to a lower fibre cross-section (FCS) and lower fibre density and cross-section (FDC) in the posterior corpus callosum and its tapetal fibres, compared to controls. Higher FDC in the chemotherapy subgroup and higher FCS in the whole study group were observed in the anterior thalamic radiations. None of the psycho-behavioural parameters correlated significantly with any of the brain differences in the study group or chemotherapy subgroup.
Prenatal exposure to maternal cancer and its treatment might affect local grey and white matter structure, but not functional connectivity or global organization. While platinum-based therapy was identified as a potential risk factor, this was not the case for chemotherapy in general.
This project has received funding from the European Union's Horizon 2020 research and innovation program (European Research council, grant no 647,047), the Foundation against cancer (Stichting tegen kanker, grant no. 2014–152) and the Research Foundation Flanders (FWO, grants no. 11B9919N, 12ZV420N)
Abstract
BACKGROUND
Meningioma patients often report cognitive complaints after therapy, profoundly impacting health-related quality of life. However, prevalence of these cognitive sequelae is ...inconsistent across trials. Moreover, meningioma patients often suffer from severe anxiety after treatment compared to healthy controls, possibly adversely affecting cognition.
MATERIAL AND METHODS
In this cohort study, 41 adult WHO grade 1 and 2 meningioma patients underwent comprehensive cognitive testing, covering the domains of memory, executive functioning, visuomotor functioning, attention, and language. Cognitive scores were transformed into z-scores using normative data adjusted for age, education, and sex. Patients were categorized as cognitively impaired if at least 2 tests scores differed ≥ - 1.5 SD or if at least 1 test score differed ≥ - 2.0 SD from the reference mean. Moreover, all patients filled out an online self-report inventory, assessing anxiety. Anxiety, age at diagnosis and treatment modality were included as predictors in a linear regression model per cognitive domain. Bonferroni correction was applied to correct for multiple testing.
RESULTS
In this cohort, 26 out of 41 patients showed cognitive impairment (63,4%) and the same number reported to have higher anxiety levels compared to the norm. Patients performed worse than the norm in cognitive domains of language and visuomotor functioning. No significant differences were found in cognitive outcomes regarding therapy, being either surgery (n=31) or surgery followed by cranial radiotherapy (n=10). Age at time of diagnosis was the only significant predictor of language (p=.005) and attention (p=.015) performance, with worse performance in case of diagnosis at younger age. No impact of anxiety nor treatment modality was found in this study.
CONCLUSION
More than half of meningioma patients showed to be cognitively impaired after surgery with or without radiotherapy treatment, mostly in domains of language and visuomotor functioning. Younger patients could be affected more by language and attention difficulties in their daily lives. Given their more active stage in life, this can have an important impact. This effect was independent of emotional functioning. These findings will need to be validated in larger prospective longitudinal trials.
Abstract
BACKGROUND
Although cognitive impairment is a serious and prevalent long-term side effect in adult glioma survivors after therapy, predictive imaging-based markers remain inconsistent to ...date. Structural brain network topology could be altered by both the tumor and its’ treatment through reorganization of hubs (i.e. highly interconnected nodes). Here, we explored the role of nodal hub-related graph metrics in higher cognitive functioning.
MATERIAL AND METHODS
48 WHO grade 2-3 adult glioma survivors (>1 year post-therapy) and 42 matched controls, underwent a cognitive assessment, covering five cognitive domains. Cognitive scores were transformed into w-scores, corrected for age and education. In addition, weighted nodal graph metrics were calculated based on diffusion weighted imaging, using multi-shell multi-tissue constrained spherical deconvolution and anatomically-constrained tractography. Hubs (hub score≥2) were calculated based on 4 nodal metrics, in which the 20% nodes with highest nodal strength and betweenness centrality, and lowest clustering coefficient and characteristic path length received 1 point (score 0-4). Significant differences in nodal graph metrics between patients and controls, and hubs versus non-hubs were tested in a repeated measures ANOVA, using Bonferroni correction for multiple testing. Significant group differences in nodal graph metrics were correlated to cognitive scores per domain.
RESULTS
In healthy controls 12/78 nodes were defined as hubs, i.e. the bilateral postcentral, precentral, superior frontal, parietofrontal, superior parietal gyri, thalamus and putamen. In glioma survivors, the left superior-parietal region and left putamen had a significantly lower likelihood of being a hub (p<.001). These specific areas showed assortativity to be positively correlated with attention, language and executive function (r(90)>.51, p<.001) and characteristic path length to be negatively correlated with all cognitive domains (r(90)>.51, p<.001). Nodal metrics of clustering coefficient, characteristic path length, local efficiency and assortativity were significantly different between groups in both hub and non-hub regions (both p<.001). Except for betweenness centrality, all nodal metrics strongly correlated with cognitive outcomes, occurring more often in hubs (33-50%) than intermediate hubs (10-33%) or non-hubs (4-12%).
CONCLUSION
Reorganization of hubs in the brain network is frequently observed in this cohort of glioma survivors compared to healthy controls. Hub connectivity seems to be important in cognitive functioning, more than for non-hub regions. Therefore, structural nodal hub-related graph metrics might be important to consider in predicting cognitive outcomes in glioma survivors.
Abstract
Background
Long-term survival can be achieved in an increasing number of glioma patients after treatment. Therefore, safeguarding these survivors’ quality of life (QoL) is essential. ...Neurocognitive decline arises in many young patients, placing a heavy burden on the social and economic aspects of the patients’ lives. A lot of debate is currently ongoing regarding the prevalence of neurocognitive impairment and individual predictors of whom is susceptible for such side effect.
Material and Methods
In this cross-sectional study, 37 WHO grade 2-3 adult glioma survivors, at least one year after multimodal therapy, were tested using a comprehensive neurocognitive test battery covering multiple cognitive domains. Neurocognitive test scores were converted into z-scores using country-specific normative data. Cognitive impairment was defined as a z-score lower or equal to -1.50 for each subtest. Age, time since multimodal therapy, radiotherapy treatment and tumour location were included as predictors in a linear regression model per outcome (n=12).
Results
In this cohort, 29 patients (78%) showed a test score below the predefined cutoff on at least one cognitive test. The percentage of patients who showed test-specific cognitive impairment ranged from 8.1% to 56.76% per test. Fine motor skills, verbal memory, processing speed and executive functioning were the most commonly affected cognitive domains. In this study, the variability in processing speed performance was associated with age (TMT A, p=0.03), time since therapy (WAIS-IV coding, p=0.02) and tumour location. In these measures, poorer outcomes were observed with increasing age, longer time since therapy and in patients with gliomas located in the left frontal lobe. Moreover, age showed to be a significant predictor of verbal memory, with poorer outcomes on the HVLT-R delayed recall task with increasing age (p=0.04). Tumour location predicted working memory performance, as patients with right parietal tumours (p=0.03) showed significantly worse on the WAIS-IV digit span task.
Conclusion
These preliminary data underline the various alterations of neurocognitive functioning in glioma survivors after multimodal therapy. Therefore, future research needs to shift towards a patient-tailored approach. The next step in this study will be to link these neurocognitive data to advanced neuroimaging data to explore the potential predictive value of imaging markers for neural damage and cognitive outcomes, paving the path to innovative treatment planning techniques.
Defining homogeneous subgroups of bipolar disorder (BD) is a major goal in personalized psychiatry and research. According to the neurodevelopmental theory, age at onset may be a key variable. As ...potential trait markers of neurodevelopment, cognitive and functional impairment should be greater in the early form of the disease, particularly type 1 BD (BD I). The age at onset was assessed in a multicenter, observational sample of 4190 outpatients with BD. We used a battery of neuropsychological tests to assess six domains of cognition. Functioning was measured using the Functioning Assessment Short Test (FAST). We studied the potential moderation of the type of BD on the associations between the age at onset and cognitive and functioning in a subsample of 2072 euthymic participants, controlling for potential clinical and socio-demographic covariates. Multivariable analyses showed cognition to not be impaired in individuals with early (21-30 years) and very early-life (before 14 years) onset of BD. Functioning was equivalent between individuals with early and midlife-onset of BD II and NOS but better for individuals with early onset of BD I. In contrast, functioning was not worse in individuals with very early-onset BD I but worse in those with very early-onset BD II and NOS. Early-life onset BDs were not characterized by poorer cognition and functioning. Our results do not support the neurodevelopmental view that a worse cognitive prognosis characterizes early-life onset BD. This study suggests that functional remediation may be prioritized for individuals with midlife-onset BD I and very early life onset BD 2 and NOS.
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