Cognitive Function In Survivors Research Articles

Longitudinal Assessment of Cognitive Function in Survivors of Testicular Germ Cell Tumor.

Survivors of testicular germ cell tumor (TGCT) may experience long-term cognitive changes. The aim of our prospective study was to longitudinally assess cognitive function among TGCT survivors to identify potential lasting cognitive changes over a period of 5 yr. TGCT survivors (n=151) completed Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaires annually, with median time to first follow-up visit (FUV) of 8 (range 4-24) yr since completion of treatment. Treatment after orchiectomy included: active surveillance (AS) alone (n=21); chemotherapy (CTx; n=109); radiotherapy (RT) to the retroperitoneum (n=11); and combined CTx + RT (n=10). Scores for four FACT-Cog domains and overall cognitive scores were evaluated annually for 5 yr. In a subgroup analysis we compared results for survivors who received cisplatin at a dose of <400 mg/m2 (n=48) versus ≥400mg/m2 (n=70). The CTx + RT group had persistently lower scores for the perceived cognitive abilities (CogPCA) domain annually between the first and fifth FUVs in comparison to the AS group (all p<0.05), with lower overall cognitive scores from the second to the fifth FUV (all p<0.03). The group that received ≥400mg/m2 cisplatin had lower CogPCA scores at the first and second FUVs, and lower overall cognitive scores at the second FUV in comparison to the AS group. However, no significant change in cognitive scores across all domains was observed over 5 yr for all survivors. Cognitive impairment in TGCT survivors persisted over long-term follow-up. Survivors who received both CTx and RT consistently had the worst cognitive performance at all FUVs over a 5-yr period. In addition, survivors who received a higher cisplatin dose showed worse cognitive function at all FUVs. Our study results show that survivors of testicular cancer experienced long-term cognitive dysfunction that persisted over time. Survivors who underwent both chemotherapy and radiotherapy and those who received a higher dose of chemotherapy had the worst cognitive problems.

Effects of Vitamin B 12 Supplementation on Cognitive Function in Survivors of Hemorrhagic Stroke

Background: Hemorrhagic stroke often leads to significant cognitive deficits in survivors. Vitamin B12 plays a crucial role in neurological functions, suggesting its potential in cognitive recovery post-stroke. This retrospective cohort study explored the impact of Vitamin B12 supplementation on cognitive function in hemorrhagic stroke survivors, a subject that holds substantial importance in stroke rehabilitation and patient care. Objective: The primary objective was to evaluate the effectiveness of Vitamin B12 supplementation in improving cognitive function, as measured by MMSE and MoCA scores, in adults who have recently survived a hemorrhagic stroke. Methods: The study included 75 adults diagnosed with hemorrhagic stroke within the last six months. Participants were administered a daily oral dose of 1000 mcg of Vitamin B12 for three months. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at the start and end of the supplementation period. Additionally, Vitamin B12 levels were measured at baseline and after three months to gauge the physiological uptake of the supplement. Results: The study observed significant improvements in cognitive function, with the MMSE score increasing by an average of 2.2 (p=0.0463) and the MoCA score by 5.8 (p=0.0410). There was also a notable average increase of 400 pg/mL in Vitamin B12 levels (p&lt;0.05). The supplementation was generally well-tolerated, with only 8% of participants reporting minor adverse effects, a rate not statistically significant (p&gt;0.05). Conclusion: The study provides preliminary evidence that Vitamin B12 supplementation may positively impact cognitive function in survivors of hemorrhagic stroke. However, due to the study's limitations, further extensive research is necessary to corroborate these findings and to deepen our understanding of the role of Vitamin B12 in post-stroke cognitive recovery.

Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest

The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. Randomization 1:1 to temperature control with targeted hypothermia at 33 °C or targeted normothermia and early treatment of fever (37.8 °C or higher). Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P = .46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P = .37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P = .62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common. ClinicalTrials.gov Identifier: NCT02908308.

Inhibition of microRNA-200c preserves astrocyte sirtuin-1 and mitofusin-2, and protects against hippocampal neurodegeneration following global cerebral ischemia in mice.

Memory impairment remains a leading disability in survivors of global cerebral ischemia, occurring secondary to delayed neurodegeneration of hippocampal cornu ammonis-1 (CA1) neurons. MicroRNA-200c (miR-200c) is induced following ischemic stress and we have previously demonstrated that pre-treatment with anti-miR-200c is protective against embolic stroke in mice. In the present study we assessed the role of miR-200c on CA1 neurodegeneration, sirtuin-1 (SIRT1), and mitochondrial dynamic protein expression in a mouse model of transient global cerebral ischemia and in vitro in primary mouse astrocyte cultures after simulated ischemia. Mice were subjected to 10 min bilateral common carotid artery occlusion plus hypotension with 5% isoflurane. After 2 h recovery mice were treated with intravenous injection of either anti-miR-200c or mismatch control. Memory function was assessed by Barnes maze at post-injury days 3 and 7. Mice were sacrificed at post-injury day 7 for assessment of brain cell-type specific expression of miR-200c, SIRT1, and the mitochondrial fusion proteins mitofusin-2 (MFN2) and OPA1 via complexed fluorescent in situ hybridization and fluorescent immunohistochemistry. Global cerebral ischemia induced significant loss of CA1 neurons, impaired memory performance and decreased expression of CA1 SIRT1, MFN2, and OPA1. Post-injury treatment with anti-miR-200c significantly improved survival, prevented CA1 neuronal loss, improved post-injury performance in Barnes maze, and was associated with increased post-injury expression of CA1 SIRT1 and MFN2 in astrocytes. In vitro, primary mouse astrocyte cultures pre-treated with miR-200c inhibitor prior to oxygen/glucose deprivation preserved expression of SIRT1 and MFN2, and decreased reactive oxygen species generation, whereas pre-treatment with miR-200c mimic had opposite effects that could be reversed by co-treatment with SIRT1 activator. These results suggest that miR-200c regulates astrocyte mitochondrial homeostasis via targeting SIRT1, and that CA1 astrocyte mitochondria and SIRT1 represent potential post-injury therapeutic targets to preserve cognitive function in survivors of global cerebral ischemia.

Characterization of Cognitive Function in Survivors of Diffuse Gliomas Using Morphometric Correlation Networks.

This pilot study investigates structural alterations and their relationships with cognitive function in survivors of diffuse gliomas. Twenty-four survivors of diffuse gliomas (mean age 44.5 ± 11.5), from whom high-resolution T1-weighted images, neuropsychological tests, and self-report questionnaires were obtained, were analyzed. Patients were grouped by degree of cognitive impairment, and interregional correlations of cortical thickness were computed to generate morphometric correlation networks (MCNs). The results show that the cortical thickness of the right insula (R2 = 0.3025, p = 0.0054) was negatively associated with time since the last treatment, and the cortical thickness of the left superior temporal gyrus (R2 = 0.2839, p = 0.0107) was positively associated with cognitive performance. Multiple cortical regions in the default mode, salience, and language networks were identified as predominant nodes in the MCNs of survivors of diffuse gliomas. Compared to cognitively impaired patients, cognitively non-impaired patients tended to have higher network stability in network nodes removal analysis, especially when the fraction of removed nodes (among 66 nodes in total) exceeded 55%. These findings suggest that structural networks are altered in survivors of diffuse gliomas and that their cortical structures may also be adapting to support cognitive function during survivorship.

Characterization of cognitive function in survivors of diffuse gliomas using resting-state functional MRI (rs-fMRI)

As treatments for diffuse gliomas have advanced, survival for patients with gliomas has also increased. However, there remains limited knowledge on the relationships between brain connectivity and the lasting changes to cognitive function that glioma survivors often experience long after completing treatment. This resting-state functional magnetic resonance imaging (rs-fMRI) study explored functional connectivity (FC) alterations associated with cognitive function in survivors of gliomas. In this pilot study, 22 patients (mean age 43.8 ± 11.9) with diffuse gliomas who completed treatment within the past 10 years were evaluated using rs-fMRI and neuropsychological measures. Novel rs-fMRI analysis methods were used to account for missing brain in the resection cavity. FC relationships were assessed between cognitively impaired and non-impaired glioma patients, along with self-reported cognitive impairment, non-work daily functioning, and time with surgery. In the cognitively non-impaired patients, FC was stronger in the medial prefrontal cortex, rostral prefrontal cortex, and intraparietal sulcus compared to the impaired survivors. When examining non-work daily functioning, a positive correlation with FC was observed between the accumbens and the intracalcarine cortices, while a negative correlation with FC was observed between the parietal operculum cortex and the cerebellum. Additionally, worse self-reported cognitive impairment and worse non-work daily functioning were associated with increased FC between regions involved in cognition and sensorimotor processing. These preliminary findings suggest that neural correlates for cognitive and daily functioning in glioma patients can be revealed using rs-fMRI. Resting-state network alterations may serve as a biomarker for patients’ cognition and functioning.

NIMG-52. CHARACTERIZATION OF COGNITIVE FUNCTION IN SURVIVORS OF DIFFUSE GLIOMAS USING MORPHOMETRIC CORRELATION NETWORKS (MCN)

Abstract Advanced multimodality treatments have led to improved survival and quality of life for patients with diffuse gliomas, and widespread functional reorganization has been reported to be associated with improved cognitive function. However, investigation of morphological alterations in patients with diffuse gliomas has been problematic, largely due to the tumor resection cavities. This pilot study has overcome these challenges and aims to characterize the relationship between structural plasticity and cognitive function in survivors of diffuse gliomas. High-resolution T1 weighted images were collected from 24 patients with diffuse gliomas (mean age 44.5 ± 11.5) who had completed their treatment within the previous ten years. Interregional correlations of cortical thickness were computed to establish morphometric correlation networks (MCN) for twelve cognitively impaired and twelve non-impaired glioma patients, as well as correlated with self-reported cognitive impairment. Our findings demonstrated that both cognitively impaired (σ=1.5979) and non-impaired (σ=1.3683) glioma patients have a small world architecture in disrupted morphological networks. Although the left fusiform (p=0.0409), left inferior (p=0.0209), and temporal (p=0.0173) gyri were observed to be thicker in non-impaired patients, the robustness of their morphological network was weak and easily vulnerable to pathological attacks and neurological deterioration. Furthermore, regions such as the superior temporal gyrus (p=0.0126) and rostral middle frontal gyrus (p=0.0148) were not only identified as predominant nodes in the MCN of patients but were also found to have greater gray matter thickness, which is associated with better FACT-cognitive function. Together, these results support our hypothesis that a widespread morphological network is altered in survivors of diffuse gliomas. Predominant regions obtained by topological analysis may lead to reliable imaging biomarkers that help evaluate patients’ cognition and ability to function.

Nurses’ perceptions of cognitive function in survivors after cardiac arrest – A qualitative study

Nurses’ perceptions of cognitive function in survivors after cardiac arrest : a qualitative study

Cognitive function in survivors from out-of-hospital cardiac arrest

There are potential concerns about the development of severe neurological sequelae or coma in patients surviving from out-of-hospital cardiac arrest (OHCA). Therefore, emergency medical services (EMS) must be aware of neurological outcome of such patients at hospital discharge.

Abstract 3275: A novel approach to treat medulloblastoma: The omega-3 fatty acids DHA and EPA reduce medulloblastoma tumor growth in vitro and in vivo

Abstract Background: The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exert antitumoral properties shown in several cancer types. DHA is found in abundance in the brain and is of importance in normal brain development and maintenance of function including cognitive functions. Medulloblastoma is the most common malignant CNS tumor of childhood. Intensive multimodal treatment is necessary including surgery, radiotherapy and chemotherapy. However, treatment often results in significant neurological sequelae and the risk of resistant relapses is still significant. The neuroprotective and antitumoral properties of omega-3 could therefore be of great benefit. Our aim was to investigate the effect of DHA and EPA on medulloblastoma in vitro and in vivo. Methods: In a panel of medulloblastoma cell lines the cytotoxic activity of DHA and EPA was studied using cell viability assays. The molecular mechanisms were characterized using cell- and molecular biology techniques. Mice with human medulloblastoma xenografts were treated with; DHA alone or with DHA and EPA for 30 days from time of tumor take while tumor growth was monitored. Control mice were fed with normal chow. The incorporation of fatty acids was analyzed in tumors, erythrocytes and brain tissue by LS-MS/MS. Results: DHA and EPA induced medulloblastoma cell toxicity with IC50 values ranging from 1.9 to 68 μM in six medulloblastoma cell lines. DHA reduced the prostaglandin E2 production, indicating a possible mechanism of action. In vivo, omega-3 supplementation resulted in significant reduction of tumor growth when established tumors were treated. DHA levels were increased in both tumor tissue and erythrocyte membrane compared to control. The in vivo treatment was non-toxic. Conclusions: DHA and EPA exert toxic effect on medulloblastoma cells in vitro and reduce tumor growth in vivo. These omega-3 fatty acids could therefore be good candidates for improving current therapy and at the same time protect healthy neurons from therapy-induced toxicity promoting cognitive function in survivors. Thus, omega-3 fatty acid supplementation has the potential of reducing tumor growth as well as reducing sequelae. Citation Format: Linda M. Ljungblad, John-Inge Johnsen, Malin Wickström, Per Kogner, Helena Gleissman. A novel approach to treat medulloblastoma: The omega-3 fatty acids DHA and EPA reduce medulloblastoma tumor growth in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3275. doi:10.1158/1538-7445.AM2015-3275

Circulation: Clinical Summaries.

Circulation: Clinical Summaries.

Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C.

Target temperature management is recommended as a neuroprotective strategy after out-of-hospital cardiac arrest. Potential effects of different target temperatures on cognitive impairment commonly described in survivors have not been investigated sufficiently. The primary aim of this study was to evaluate whether a target temperature of 33°C compared with 36°C was favorable for cognitive function; the secondary aim was to describe cognitive impairment in cardiac arrest survivors in general. Study sites included 652 cardiac arrest survivors originally randomized and stratified for site to temperature control at 33°C or 36°C within the Target Temperature Management trial. Survival until 180 days after the arrest was 52% (33°C, n=178/328; 36°C, n=164/324). Survivors were invited to a face-to-face follow-up, and 287 cardiac arrest survivors (33°C, n=148/36°C, n=139) were assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed was more affected among cardiac arrest patients, but results for memory and executive functioning were similar. Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest survivors was also common in matched control subjects with ST-segment-elevation myocardial infarction not having had a cardiac arrest. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01946932.

Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD.