Objective: To provide a comprehensive overview of the interventions and their effectiveness used to simultaneously improve fatigue and neurocognitive impairment in patients with progressive neurological disorders. Data sources: A systematic search was conducted in four databases (PubMed, Embase.com, APA PsycInfo, and CINAHL). Study selection: Two independent reviewers selected interventional studies that reported on the effects of symptom management interventions on both patient-reported fatigue and neurocognitive outcomes. Data extraction: Study details, intervention characteristics, assessment tools, and outcomes were extracted. The results were synthesized through a narrative approach. Data synthesis: We identified 3188 studies, of which 91 were included (MS = 80, Parkinson's disease = 8, glioma = 3). Studies investigated physical activity (n = 26), pharmacological treatments (n = 25), cognitive rehabilitation (n = 12), multimodal interventions (n = 6), mind-body and psychological interventions (n = 4), noninvasive neurostimulation (n = 4), cannabis derivatives (n = 3), and other interventions (n = 7). Overall, study designs and intervention protocols were heterogeneous across studies. Of the 91 identified studies, 24 demonstrated a positive effect on both fatigue and neurocognitive functioning (referred to as F + NCF+). Particularly, aerobic physical activity demonstrated consistent improvements in fatigue and neurocognitive functioning (12/26 studies F + NCF+). Other interventions were less successful; for example, only 2/25 pharmacological interventions and 2/12 cognitive rehabilitation programs were F + NCF+. Across studies, methodologies including guidance by a healthcare provider, on-site program administration, group-based elements, and interventional personalization contributed to intervention success. Conclusions: A considerable number of heterogeneous studies explored various interventions. However, only a subset instigated improvement in fatigue and neurocognitive impairments. Physical activity emerged as a particularly promising intervention, potentially alleviating both fatigue and neurocognitive impairment across progressive neurological disorders. There is an unmet need for personalized and guided interventions targeting these co-occurring symptoms, which should be addressed in future studies.

INTRODUCTION:Information processing speed (IPS) is frequently impaired in people with multiple sclerosis (PwMS) and can potentially interfere with functioning in other cognitive domains. A relationship between IPS and visuospatial memory has been shown, but the impact of IPS on the separate components of visuospatial memory remains unclear. In this study, we aim to investigate the association between IPS impairment and encoding, active and passive retrieval, and learning indices of visuospatial memory in PwMS. METHODS:Cross-sectional data from 92 PwMS with cognitive complaints and 29 matched healthy controls (HCs) were retrospectively analyzed. IPS and visuospatial memory were measured using the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test - Revised (BVMT-R), respectively. Hierarchical regression analyses were performed to assess the predictive value of IPS impairment (z-score ≤-1.5) for visuospatial encoding, active and passive retrieval, as well as learning indices scores. RESULTS:In total, 47.8% of PwMS were impaired on the SDMT. IPS impairment significantly predicted lower performance on the second (ß = -0.26, p = 0.011) and third (ß = -0.29, p = 0.003) learning trials, active retrieval (ß = -0.33, p < 0.001), and learning index (ß = -0.28, p = 0.003) of the BVMT-R in PwMS. No significant association was found between IPS impairment and the initial learning and passive retrieval scores. In HCs, no association between IPS and BVMT-R performance was found. CONCLUSION:PwMS with IPS impairment perform worse on visuospatial learning and memory, particularly in the later encoding phases and active retrieval of information. These findings highlight the importance of taking IPS impairment into account when interpreting visuospatial memory performance in MS.

Fatigue is a prevalent and debilitating symptom for patients with incurable cancer. Cognitive behavioral therapy (CBT) can significantly reduce cancer-related fatigue in this patient group. However, implementation of CBT into clinical care is difficult as the intervention is time-intensive, costly, and requires face-to-face consultations with a specialized CBT therapist. Since nurses already support patient with symptom management, including fatigue, internet supported CBT delivered by nurses could be a promising alternative for patients with incurable cancer. The primary aim of this study is to determine the non-inferiority of nurse-led web-based CBT in its effect on cancer-related fatigue, compared to CBT provided by CBT therapists. The study is a prospective, non-randomized study using historical cohorts as the benchmark for comparison. Severely fatigued patients with incurable cancer of a solid tumor receive a 12-week nurse-led web-based CBT intervention. Primary and secondary outcome measures are assessed at baseline, post-intervention (14 weeks), and follow-up (26 weeks). The primary outcome measure is fatigue severity assessed with the Checklist Individual Strength (CIS-subscale fatigue severity). Secondary outcomes include functional impairment, quality of life and fatigue assessed with EORTC-QLQ-C30, and health care costs. Primary and secondary outcomes of the TIRELESS study and the benchmark are compared to determine non-inferiority. Non-inferiority of fatigue reduction is concluded if the upper bound of the one-sided 95

Background:Although physical activity may play a significant role in enhancing quality of life for glioma patients, its integration into clinical care remains underexplored. This study assessed the experiences, perspectives, and barriers of healthcare professionals in promoting physical activity for glioma patients. Methods:An online survey with 19 questions was distributed to Dutch healthcare professionals registered with the Dutch Neuro-Oncology Society (LWNO). Additionally, professionals were individually asked to remind and invite their colleagues to participate. Participants provided informed consent. Results:Fifty-five professionals from 20 centers completed the survey, mainly neurologists (35%) and nurses (33%). Most professionals (58%) indicated receiving frequent questions about physical activity, particularly regarding safety and appropriate activities. Additionally, 76% stated they often proactively provide advice, recommending low-intensity activities like walking. Key barriers to making such recommendations included limited information materials (37%), knowledge (33%), and referral options (27%). Professionals' concerns about physical activity included risks of overexertion and patient discouragement if activity would prove too challenging. Despite these challenges, 89% supported integrating physical activity into glioma care, and 56% expressed a need for specific guidelines. While professionals believe in the benefits for symptom management and quality of life, 62% were neutral about the strength of supporting evidence. Conclusions:In this sample, physical activity is frequently discussed in glioma care, but recommendations are mostly inappropriate due to limited knowledge, resources, and guidance. Existing guidelines are rarely applied in practice. Future research should accumulate evidence, develop tailored guidelines, and equip professionals with tools to truly integrate physical activity into practice.

BACKGROUND:While severe fatigue is common in patients with diffuse glioma, no evidence-based treatment is currently available. The objective of this RCT was to evaluate the efficacy of blended cognitive behavioral therapy (bCBT) for severe fatigue. METHODS:Severely fatigued patients (Checklist Individual Strength, fatigue-severity subscale [CIS-fatigue] ≥ 35) with diffuse glioma and stable disease were randomized to 12 weeks of bCBT or a waiting list condition (WLC). The primary endpoint was fatigue severity 2 weeks after intervention. This Bayesian adaptive trial included prespecified interim analyses for efficacy at n = 40, 50, 60, 70, and 80. Secondary outcomes-health-related quality of life (HRQoL), anxiety, future uncertainty, and depression-were assessed at 2 and 12 weeks after intervention. RESULTS:The trial was stopped for efficacy at the first interim analysis. Of 47 patients randomized, 40 patients reached the primary endpoint (mean age 53 years, 47% female). The posterior probability that CIS-fatigue scores were lower with bCBT than with WLC was 99.94%, with a large standardized effect size (Cohen's d) of 1.12 [95% CI: 0.43-1.81]. At 2 weeks after intervention, 68% of patients were no longer severely fatigued after bCBT, compared to 24% in WLC. At 12 weeks follow-up, fatigue was still significantly lower in the bCBT group compared to WLC (d = 1.22). bCBT also demonstrated beneficial effects (d = 0.42-1.19) on anxiety, HRQoL, and future uncertainty. CONCLUSIONS:bCBT significantly reduces fatigue and improves anxiety and HRQoL in patients with diffuse glioma. These findings enable evidence-based supportive care strategies for reducing fatigue and enhancing HRQoL in this population.

Background ETERNITY was a retrospective and prospective cohort study investigating long-term (≥5 years) survival in patients with glioblastoma. We assessed the longitudinal course of neurocognitive function (NCF) and its determinants in a subgroup of patients with glioblastoma, IDH-wildtype, or astrocytoma, IDH-mutant, CNS WHO grade 4. Methods NCF was assessed at baseline and every 6 months using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test. Scores were converted to age-, sex-, and education-adjusted Z-scores and classified as impaired or unimpaired (Z ≤ -1.5). Linear mixed models were used to analyze NCF trajectories and associations with patient and tumor characteristics. Results At baseline (mean 9 years post-diagnosis, range 5-21 years), 145 of 185 patients (78%) were impaired on ≥1 test outcome. Impairment rates varied between 17.4% (HVLT-R delayed recognition) and 58.7% (TMT B). NCF remained largely stable over time, with a small decline in HVLT-R delayed memory. Left-sided and temporal tumor location were negatively associated with poorer NCF (p’s.01 to.03). Frontal tumor location was associated with higher psychomotor speed and cognitive flexibility (p’s <.001). Patients with IDH-mutant tumors performed worse on delayed recognition, whereas IDH mutation and MGMT promoter methylation were linked to improved phonemic fluency over time. Conclusions The majority of long-term survivors with astrocytoma, IDH-mutant, CNS WHO grade 4, and glioblastoma IDH-wildtype show neurocognitive impairment. Nonetheless, NCF is generally stable, with tumor location and molecular features associated with specific outcomes. These insights can help guide patient counseling and personalized care.

Type 1 diabetes-related cognitive declines suggest cortical involvement, despite cortical volume and thickness failing to account for these changes. The local gyrification index (LGI), which quantifies the complexity of cortical folding, could therefore provide additional information about cerebral integrity. This study aimed to determine differences in LGI in type 1 diabetes (T1D) in relation to the white matter integrity of connecting fibers and cognitive functioning. Fifty-one T1D participants with microangiopathy, 53 without, and 49 healthy controls underwent MR-imaging and neuropsychological assessment. LGI was calculated using FreeSurfer6. Probabilistic tractography was performed with MRtrix3. Group analyses were adjusted for age, sex, systolic blood pressure; and for multiple comparisons using Family Wise Error (FWE). Mediation analysis was performed with Python. LGI was broadly reduced across T1D participants, primarily driven by those with microangiopathy (all PFWE < 0.05), especially in cortical areas connected by the arcuate fasciculus and forceps major. Lower LGI was associated with poorer arcuate fasciculus and forceps major integrity – tracts selected because their fibers connect the cortical regions exhibiting decreased gyrification in type 1 diabetes – and cognition (all P < 0.05). Mediation analyses revealed that cortical gyrification partly mediates the relationship between lower white matter integrity and reduced cognitive performance. LGI reductions had a posterior predominance in the brain in adults with T1D and microangiopathy, and associated with cognitive decrements and poorer white matter integrity. Mediation analyses further suggested a critical role of reduced cortical gyrification in linking lower white matter integrity to poorer cognitive performance.

Introduction Oligodendroglioma (ODG) is a rare type of brain tumour, typically diagnosed in younger adults and associated with prolonged survival following treatment. The current standard of care is maximal safe debulking surgery, radiotherapy (RT) and adjuvant procarbazine, lomustine and vincristine (PCV) chemotherapy. Patients may experience long-term treatment-related toxicities, with RT linked to impairments of neurocognitive function (NCF) and health-related quality of life (HRQoL). With proton beam therapy (PBT), radiation dose falls off sharply beyond the target with reduced normal brain tissue radiation doses compared with photon RT. Therefore, PBT might result in reduced radiation-induced toxicity compared with photon RT.Methods and analysis APPROACH is a multicentre open-label phase III randomised controlled trial of PBT versus photon RT in patients with ODG, investigating the impact of PBT on long-term NCF measured using the European Organisation for Research and Treatment of Cancer (EORTC) Core Clinical Trial Battery Composite (CTB COMP). The trial will randomise 246 participants from 18 to 25 UK RT sites, allocated 1:1 to receive PBT or photon RT, with PBT delivered at one of the two UK PBT centres. Participants with grade 2 and grade 3 ODG will receive 54 Gy in 30 fractions and 59.4 Gy in 33 fractions, respectively, followed by 6×6-weekly cycles of PCV chemotherapy. The trial contains staged analyses, with an internal pilot for feasibility of recruitment at 12 months, early assessment of efficacy at 2 years, futility assessment and final primary endpoint comparison of NCF between arms at 5 years. Secondary endpoints include additional NCF, treatment compliance, acute and late toxicities, endocrinopathies, HRQoL, tumour response, progression-free survival and overall survival.Ethics and dissemination Ethical approval was obtained from Newcastle North Tyneside REC (reference 22/NE/0232). Final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors (ICMJE) guidelines.Trial registration number ISRCTN:13390479.

BACKGROUND:Patients with oligodendroglioma have a relatively favorable prognosis. The long-term impacts of the tumor itself and its treatment on health-related quality of life (HRQOL) and cognition remain largely unclear. We investigated associations between treatment and functioning of survivors of oligodendroglioma. METHODS:In this cross-sectional observational study, patients with oligodendroglioma, isocitrate dehydrogenase-mutant and 1p/19q-codeleted, diagnosed ≥ 5 years ago, were recruited. Patients completed patient-reported outcome measures (EORTC QLQ-C30; BN20; MOS Cognitive Complaints Scale) and cognitive tests (HVLT-R, TMT, COWAT). Associations between HRQOL and cognition outcomes, and clinical variables (time since diagnosis; age at diagnosis; progression; tumor location; treatments delivered; time since treatment; current medication) were explored with regression analyses. RESULTS:In total, 237 patients M = 9.9 years postdiagnosis (SD = 4.2, range 5.0-25.8) took part from 33 sites across 9 countries. Clinically relevant levels of impairment were noted in >40% of patients on EORTC QLQ-C30 scales for cognitive functioning (56.1%), emotional functioning (49.8%), fatigue (45.1%), and physical functioning (40.5%). In individuals, cognitive impairment ranged from 17.7% for processing speed to 46.0% for episodic verbal memory (delayed recall). Among other clinical factors such as current use of antiseizure medication or antidepressants, age, disease progression, time since diagnosis and time since treatment, and radiotherapy treatment (ever received) was linked to HRQOL and cognitive functioning outcomes (posthoc analyses for cumulative radiotherapy dose: not significant). CONCLUSIONS:In oligodendroglioma survivors, HRQOL and cognitive impairment are prevalent even years into follow-up. Supportive care and rehabilitation should be prioritized to mitigate these challenges and improve daily functioning. TRIAL REGISTRATION:NCT04708548.

Background:Glioma patients frequently suffer from executive functioning (EF) deficits. The underlying neurophysiological mechanisms remain poorly understood. Studies have revealed bidirectional interactions between gliomas and their surroundings with neuronal activity promoting tumor growth and vice versa. Hyperactivity holds prognostic value for tumor progression, but how does pathological activity relate to neurocognitive deficits? We investigated the relationship between brain activity in the neurocognitively relevant frontoparietal network (FPN) and the peritumoral area and EF in glioma patients. Methods:We conducted neuropsychological assessments and measured resting-state brain activity using magnetoencephalography in 37 glioma patients (preoperatively and at 1-year follow-up) and 25 matched healthy controls (HCs). Broadband power and offset served as proxies for neuronal activity and were averaged separately for the peritumoral area and the FPN regions ipsilateral and contralateral to the tumor hemisphere. EF was operationalized with the concept-shifting and word-fluency tests. We used linear regression to relate activity and EF. Results:Brain activity became more deviant over time in the peritumoral area. While higher broadband power in the right FPN was associated with lower word fluency in HCs, there was no association between brain activity and EF in patients, neither at baseline nor longitudinally. Conclusions:These results indicate that resting-state activity might not hold clinical relevance for EF in glioma patients, while it does become more deviant over time. Patient-specific deviations in functional network properties, such as the integration of the network, may be more relevant for EF in this patient group, as a recent study in the same cohort has shown.

Purpose The rate of missing data on patient-reported health-related quality of life (HRQOL) in brain tumor clinical trials is particularly high over time. One solution to this issue is the use of proxy (i.e., partner, relative, informal caregiver) ratings in lieu of patient-reported outcomes (PROs). In this study we investigated patient–proxy agreement on HRQOL outcomes in high-grade glioma (HGG) patients. Methods Generic and disease-specific HRQOL were assessed using the EORTC QLQ-C30 and QLQ-BN20 in a sample of 501 patient–proxy dyads participating in EORTC trials 26101 and 26091. Patients were classified as impaired or intact, based on their neurocognitive performance. The level of patient–proxy agreement was measured using Lin’s concordance correlation coefficient (CCC) and the Bland–Altman limit of agreement. The Wilcoxon signed-rank test was used to evaluate differences between patients’ and proxies’ HRQOL. Results Patient–proxy agreement in all HGG patients ( N = 501) ranged from 0.082 to 0.460. Only 18.8% of all patients were neurocognitively intact. Lin’s CCC ranged from 0.088 to 0.455 in cognitively impaired patients and their proxies and from 0.027 to 0.538 in cognitively intact patients and their proxies. Conclusion While patient–proxy agreement on health-related quality of life outcomes is somewhat higher in cognitively intact patients, agreement in high-grade glioma patients is low in general. In light of these findings, we suggest to cautiously consider the use of proxy’s evaluation in lieu of patient-reported outcomes, regardless of patient’s neurocognitive status.

Olfactory dysfunction is an early, common, and progressive symptom in Parkinson’s disease (PD). Whether the decline in olfactory function is longitudinally associated with a deterioration of (non-)motor symptoms remains debated. This study aimed to investigate the longitudinal relationship between olfactory function and (non-)motor symptoms, particularly cognitive decline, in PD patients over a ten-year follow-up period. Ninety patients were assessed at baseline and after approximately ten years. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT®). (non-)Motor symptoms were evaluated using various scales and questionnaires, including the MMSE to assess global cognitive function. Linear regression was used to analyze the change in olfactory function over time in relation to changes in (non-)motor function, and to determine whether baseline olfactory test scores would be associated with (non-)motor function at follow-up. In a subset of 62 patients, in whom comprehensive cognitive testing was performed, we analyzed the longitudinal relationship between olfactory function and performance on specific cognitive tests. Statistically significant associations were found between a decrease in UPSIT® scores and decline in MMSE, and between baseline UPSIT® scores and MMSE performance at follow-up. In the subgroup with comprehensive cognitive testing, a decrease in UPSIT® scores was associated with worsening semantic fluency. Furthermore, an association was found between baseline UPSIT® score and semantic fluency at follow-up. Decline in olfactory function in PD is longitudinally associated with worsening global cognitive function, particularly a deterioration in semantic fluency. Baseline olfactory function may be predictive of later cognitive decline, especially in the semantic domain.

Background Knowledge about glioma patients' physical functioning and physical fitness throughout the disease trajectory is limited. We analyzed self-reported functioning and fitness in a large sample of glioma patients preoperatively and after primary treatment.Methods We used the physical functioning subscale of the 36-Item Short Form Health Survey (SF36) and three questions about physical fitness from the Checklist of Individual Strength (CIS20). Scores were compared to age-, sex-, and education-matched population controls, preoperatively and after treatment. In patients with repeated assessments, changes over time were analyzed. Correlations between patient, disease, and treatment characteristics and functioning and fitness at both time points, and with change over time, were explored. Analyses were performed separately for World Health Organization grade II, III, and IV glioma.Results Grade III patients had significantly lower functioning than controls, both preoperatively and after treatment, and declined over time. No significant differences with controls were found for grade II and IV patients, or for fitness. Grade II patients reported better functioning than grade III and IV preoperatively and better than grade III after treatment. Lower Karnofsky Performance Status was generally related to lower functioning and fitness, while older age, female sex, and lower education appeared in subgroup analyses. Age, neurological disabilities and tumor histology were associated with changes over time.Conclusions Grade III glioma patients showed poorer functioning than population controls, which declined over time. Grade II patients reported better outcomes than the other subgroups, although individual variability was high. These findings highlight the need for personalized approaches addressing functioning and fitness in glioma.

INTRODUCTION:Cancers of the central nervous system (CNS) include primary and metastatic tumors of varying cells of origin. These tumors may be benign or malignant, with incidence rates varying based on age, gender, and tumor type. While heterogeneous, all CNS tumors harbor risk of neurocognitive impairment, impairing patients' health-related quality of life (HRQoL). METHOD:This narrative review was informed by a targeted literature search in PubMed and Scopus, focusing on studies reporting neurocognitive deficits in patients with gliomas, primary CNS lymphomas, and metastatic CNS tumors. Articles were selected based on clinical relevance, methodological quality, and their contribution to key themes in neurocognitive outcomes among patients with CNS tumor: impact of tumor type, location, and treatment modalities, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. The influence of adjunctive treatments such as corticosteroids and antiepileptics on neurocognitive function was also examined. Data synthesis included neurocognitive assessment measures, patient demographics, and potential modifiers such as brain plasticity and psychological distress. This approach was designed to support an integrative, expert-informed synthesis rather than a systematic or exhaustive review. RESULTS:Findings indicate that neurocognitive deficits are prevalent among CNS tumor patients, with impairments in memory, attention, processing speed, and executive function. Tumor location significantly influences the type and severity of deficits, with frontal and temporal lobe involvement being particularly detrimental. Treatment modalities contribute to neurocognitive decline, with radiotherapy having cumulative negative effects. Psychological distress and individual brain resilience further modulate outcomes, highlighting the need for individualized treatment strategies. CONCLUSIONS:Neurocognitive impairment in CNS tumor patients results from both disease pathology and treatment effects. Understanding these mechanisms is crucial for developing targeted interventions, including cognitive rehabilitation and tailored treatment plans, to optimize patient outcomes. Improved management strategies incorporating neuroprotective approaches and psychological support are essential for enhancing long-term HRQoL in CNS tumor patients.

BACKGROUND:Glioma patients often exhibit neurocognitive deficits across multiple domains, yet studies typically assess these impairments separately. This study explores aggregated neurocognitive functioning (NCF), identifying distinct profiles and their clinical correlates. METHODS:NCF in glioma patients with stable disease (≥ 2 months after treatment without clinical or radiological progression) was assessed across five domains: attention, information processing speed, verbal memory, working memory, and flexibility. We used hierarchical cluster analysis to distinguish neurocognitive profiles and replicated these profiles in an independent glioma cohort. Associations between neurocognitive profiles and clinical characteristics were examined using multinomial logistic regression. RESULTS:Four distinct neurocognitive profiles were identified in both the study (N = 108) and the validation cohort (N = 185): a preserved, memory, processing/attention, and multi-domain profile. In both cohorts, 40% of patients exhibited impaired NCF, with deficits in at least one domain observed in 44% in the study cohort and 38% in the validation cohort. In the study cohort, tumor hemisphere and prior treatment with radiotherapy or combined radio- and chemotherapy were associated with processing/attention and multi-domain profiles. In both the cohorts, the multi-domain profile showed a weak association with self-perceived NCF. No other significant associations with patient, tumor, or treatment characteristics were observed. CONCLUSIONS:NCF in glioma patients can be classified into four reproducible neurocognitive profiles. Importantly, concurrent problems in NCF are highly prevalent. Neurocognitive profiles are associated with tumor laterality, previous oncological treatment, and self-perceived NCF, but not with other clinical characteristics.

Background The heterogeneous nature of cognitive impairment in people with multiple sclerosis (PwMS) hampers understanding of the underlying mechanisms and developing patient-tailored interventions. We aim to identify and classify cognitive profiles in PwMS, comparing these to cognitive status (preserved versus impaired). Methods We included 1213 PwMS (72% female, age 45.4 ± 10.7 years, 83% relapsing–remitting MS). Cognitive test scores were converted to Z -scores compared to healthy controls for the functions: attention, inhibition, information processing speed (IPS), verbal fluency and verbal/visuospatial memory. Concerning cognitive status, impaired cognition (CI) was defined as performing at Z ≤ − 1.5 SD on ≥ 2 functions. Cognitive profiles were constructed using latent profile analysis on all cognitive functions. Cognitive profiles or status was classified using gradient boosting decision trees, providing the importance of each feature (demographics, clinical, cognitive and psychological functioning) for the overall classification. Results Six profiles were identified, showing variations in overall performance and specific deficits (attention, inhibition, IPS, verbal fluency, verbal memory and visuospatial memory). Across the profiles, IPS was the most impaired function (%CI most preserved profile, Profile 1 = 22.4%; %CI most impaired profile, Profile 6 = 76.6%). Cognitive impairment varied from 11.8% in Profile 1 to 95.3% in Profile 6. Of all cognitive functions, visuospatial memory was most important in classifying profiles and IPS the least (area under the curve (AUC) = 0.910). For cognitive status, IPS was the most important classifier (AUC = 0.997). Conclusions This study demonstrated that cognitive heterogeneity in MS reflects a continuum of cognitive severity, distinguishable by distinct cognitive profiles, primarily explained by variations in visuospatial memory functioning.

Abstract BACKGROUND Patients with IDH-mutant, 1p/19-codeleted oligodendroglioma have a relatively favourable prognosis and can experience long periods of stable disease. Treatment modalities used vary, and the long-term impacts of both the tumour itself and its treatment on patient health-related quality of life (HRQOL) and cognition remain largely unclear. We aimed to investigate associations between treatment and functioning of oligodendroglioma patients ≥5 years after diagnosis. MATERIAL AND METHODS In this international cross-sectional observational study, patients with histologically and molecularly confirmed oligodendroglioma (IDH mutant, 1p/19q codeleted) diagnosed ≥5 years ago, were recruited through the European Organisation for Research and Treatment of Cancer (EORTC) networks. Diagnosis and treatment data were collected from medical records; patients completed outcomes for HRQOL (EORTC QLQ-C30; BN20), self-reported cognitive functioning (MOS Cognitive Functioning Scale) and cognitive tests (HVLT-R, TMT, COWAT) once. Associations between HRQOL and cognition outcomes, and clinical variables (time since diagnosis; progression; tumour location; treatments delivered; current medication; Karnofsky Performance Status (KPS)) were explored with regression analyses. RESULTS 242 oligodendroglioma patients on average 9.9 years post-diagnosis (sd=4.3, range=5.0-26.3) took part from 33 sites across 9 countries. Patients were M=52 years old (sd=12, range=23-78), the majority were men (N=145; 60%). Higher KPS, no radiotherapy (ever), no current medication (anxiolytics/sedatives, antidepressants, dexamethasone) were associated with better generic HRQOL outcomes (QLQ-C30 functioning scale models; R2 range 0.068-0.371, all p<.001). Higher KPS, fewer recurrences, no radiotherapy treatment (ever), and no current antidepressant use were of predictive value for better disease-specific HRQOL (BN20 multi-item scale models; R2 range 0.067-0.246, p<0.001). Fewer subjective cognitive complaints were associated with higher KPS and no current antipsychotic medication use (R2=0.153, p<0.001). Better KPS, right hemispheric tumours, longer time since diagnosis, no chemotherapy (ever), no radiotherapy (ever), and no current medication use (dexamethasone, antipsychotics) were predictive of better cognitive functioning (multivariable models R2 range 0.056-0.248, p<0.001). CONCLUSION In oligodendroglioma survivors ≥5 years after diagnosis, better HRQOL and cognitive outcomes appear consistently linked with higher KPS, no current medication use and no radiotherapy (ever); with cognitive outcomes additionally associated with chemotherapy treatment. This information can support treatment decision-making. Targeted evaluation and support for patients should be implemented to optimise clinical outcomes.