Search

Cosmic radiation experienced during space travel may increase the risk of cognitive impairment. While simulated galactic cosmic radiation (GCRsim) has led to memory deficits in wildtype (WT) mice, it has not been investigated whether GCRsim in combination with genetic risk factors for Alzheimer's disease (AD) worsens memory further in aging mice. Here, we investigated the central nervous system (CNS) effects of 0 Gy (sham) or 0.75 Gy five-ion GCRsim or 2 Gy gamma radiation (IRR) in 14-month-old female and male APP NL-F/NL-F knock-in (KI) mice bearing humanized ApoE3 or ApoE4 (APP;E3F and APP;E4F). As travel to a specialized facility was required for irradiation, both traveled sham-irradiated C57BL/6J WT and KI mice and non-traveled (NT) KI mice acted as controls for potential effects of travel. Mice underwent four behavioral tests at 20 months of age and were euthanized for pathological and biochemical analyses 1 month later. Fecal samples were collected pre- and post-irradiation at four different time points. GCRsim seemed to impair memory in male APP;E3F mice compared to their sham counterparts. Travel tended to improve cognition in male APP;E3F mice and lowered total Aβ in female and male APP;E3F mice compared to their non-traveled counterparts. Sham-irradiated male APP;E4F mice accumulated more fibrillar amyloid than their APP;E3F counterparts. Radiation exposure had only modest effects on behavior and brain changes, but travel-, sex-, and genotype-specific effects were seen. Irradiated mice had immediate and long-term differences in their gut bacterial composition that correlated to Alzheimer's disease phenotypes.

Purpose: Irradiation of the brain regions from nasopharyngeal carcinoma (NPC) radiotherapy (RT) is frequently unavoidable, which may result in radiation-induced cognitive deficit. Using deep learning (DL), the study aims to develop prediction models in predicting compromised cognition in patients following NPC RT using remote assessments and determine their relation to the quality of life (QoL) and MRI changes., Methods: Seventy patients (20-76 aged) with MRI imaging (pre- and post-RT (6 months-1 year)) and complete cognitive assessments were recruited. Hippocampus, temporal lobes (TLs), and cerebellum were delineated and dosimetry parameters were extracted. Assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE), and QLQ-H&N 43). Regression and deep neural network (DNN) models were used to predict post-RT cognition using anatomical and treatment dose features., Results: Remote cognitive assessments were inter-correlated (r > 0.9). TLs showed significance in pre- and post-RT volume differences and cognitive deficits, that are correlated with RT-associated volume atrophy and dose distribution. Good classification accuracy based on DNN area under receiver operating curve (AUROC) for cognitive prediction (T-MoCA AUROC = 0.878, TICS AUROC = 0.89, Tele-MACE AUROC = 0.919)., Conclusion: DL-based prediction models assessed using remote assessments can assist in predicting cognitive deficit following NPC RT. Comparable results of remote assessments in assessing cognition suggest its possibility in replacing standard assessments., Implications for Cancer Survivors: Application of prediction models in individual patient enables tailored interventions to be provided in managing cognitive changes following NPC RT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Whole-brain radiation therapy (WBRT) is a common treatment for brain metastases and is frequently associated with decline in neurocognitive functioning (NCF). The e4 allele of the apolipoprotein E (APOE) gene is associated with increased risk of Alzheimer disease and NCF decline associated with a variety of neurologic diseases and insults. APOE carrier status has not been evaluated as a risk factor for onset time or extent of NCF impairment in patients with brain metastases treated with WBRT., Methods and Materials: NRG/Radiation Therapy Oncology Group 0614 treated adult patients with brain metastases with 37.5 Gy of WBRT (+/- memantine), performed longitudinal NCF testing, and included an optional blood draw for APOE analysis. NCF test results were compared at baseline and over time with mixed-effects models. A cause-specific Cox model for time to NCF failure was performed to assess the effects of treatment arm and APOE carrier status., Results: APOE results were available for 45% of patients (n = 227/508). NCF did not differ by APOE e4 carrier status at baseline. Mixed-effects modeling showed that APOE e4 carriers had worse memory after WBRT compared with APOE e4 noncarriers (Hopkins Verbal Learning Test-Revised total recall [least square mean difference, 0.63; P = .0074], delayed recognition [least square mean difference, 0.75; P = .023]). However, APOE e4 carrier status was not associated with time to NCF failure (hazard ratio, 0.86; 95% CI, 0.60-1.23; P = .40). Memantine delayed the time to NCF failure, regardless of carrier status (hazard ratio, 0.72; 95% CI, 0.52-1.01; P = .054)., Conclusions: APOE e4 carriers with brain metastases exhibited greater decline in learning and memory, executive function, and the Clinical Trial Battery Composite score after treatment with WBRT (+/- memantine), without acceleration of onset of difference in time to NCF failure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Photobiomodulation (PBM) therapy on the brain employs red to near-infrared (NIR) light to treat various neurological and psychological disorders. The mechanism involves the activation of cytochrome c oxidase in the mitochondrial respiratory chain, thereby enhancing ATP synthesis. Additionally, light absorption by ion channels triggers the release of calcium ions, instigating the activation of transcription factors and subsequent gene expression. This cascade of events not only augments neuronal metabolic capacity but also orchestrates anti-oxidant, anti-inflammatory, and anti-apoptotic responses, fostering neurogenesis and synaptogenesis. It shows promise for treating conditions like dementia, stroke, brain trauma, Parkinson's disease, and depression, even enhancing cognitive functions in healthy individuals and eliciting growing interest within the medical community. However, delivering sufficient light to the brain through transcranial approaches poses a significant challenge due to its limited penetration into tissue, prompting an exploration of alternative delivery methods such as intracranial and intranasal approaches. This comprehensive review aims to explore the mechanisms through which PBM exerts its effects on the brain and provide a summary of notable preclinical investigations and clinical trials conducted on various brain disorders, highlighting PBM's potential as a therapeutic modality capable of effectively impeding disease progression within the organism-a task often elusive with conventional pharmacological interventions.

Background: We aimed to assess evidence of long-term effects of exposure to radiofrequency (RF) electromagnetic fields (EMF) on indicators of cognition, including domains of learning and memory, executive function, complex attention, language, perceptual motor ability and social cognition, and of an exposure-response relationship between RF-EMF and cognition., Methods: We searched PubMed, Embase, PsycInfo and the EMF-Portal on September 30, 2022 without limiting by date or language of publication. We included cohort or case-control studies that evaluated the effects of RF exposure on cognitive function in one or more of the cognitive domains. Studies were rated for risk of bias using the OHAT tool and synthesised using fixed effects meta-analysis. We assessed the certainty of the evidence using the GRADE approach and considered modification by OHAT for assessing evidence of exposures., Results: We included 5 studies that reported analyses of data from 4 cohorts with 4639 participants consisting of 2808 adults and 1831 children across three countries (Australia, Singapore and Switzerland) conducted between 2006 and 2017. The main source of RF-EMF exposure was mobile (cell) phone use measured as calls per week or minutes per day. For mobile phone use in children, two studies (615 participants) that compared an increase in mobile phone use to a decrease or no change were included in meta-analyses. Learning and memory. There was little effect on accuracy (mean difference, MD -0.03; 95% CI -0.07 to 0.02) or response time (MD -0.01; 95% CI -0.04 to 0.02) on the one-back memory task; and accuracy (MD -0.02; 95%CI -0.04 to 0.00) or response time (MD -0.01; 95%CI -0.04 to 0.03) on the one card learning task (low certainty evidence for all outcomes). Executive function. There was little to no effect on the Stroop test for the time ratio ((B-A)/A) response (MD 0.02; 95% CI -0.01 to 0.04, very low certainty) or the time ratio ((D-C)/C) response (MD 0.00; 95% CI -0.06 to 0.05, very low certainty), with both tests measuring susceptibility to interference effects. Complex attention. There was little to no effect on detection task accuracy (MD 0.02; 95% CI -0.04 to 0.08), or response time (MD 0.02;95% CI 0.01 to 0.03), and little to no effect on identification task accuracy (MD 0.00; 95% CI -0.04 to 0.05) or response time (MD 0.00;95% CI -0.01 to 0.02) (low certainty evidence for all outcomes). No other cognitive domains were investigated in children. A single study among elderly people provided very low certainty evidence that more frequent mobile phone use may have little to no effect on the odds of a decline in global cognitive function (odds ratio, OR 0.81; 95% CI 0.42 to 1.58, 649 participants) or a decline in executive function (OR 1.07; 95% CI 0.37 to 3.05, 146 participants), and may lead to a small, probably unimportant, reduction in the odds of a decline in complex attention (OR 0.67;95%CI 0.27 to 1.68, 159 participants) and a decline in learning and memory (OR 0.75; 95% CI 0.29 to 1.99, 159 participants). An exposure-response relationship was not identified for any of the cognitive outcomes., Discussion: This systematic review and meta-analysis found only a few studies that provided very low to low certainty evidence of little to no association between RF-EMF exposure and learning and memory, executive function and complex attention. None of the studies among children reported on global cognitive function or other domains of cognition. Only one study reported a lack of an effect for all domains in elderly persons but this was of very low certainty evidence. Further studies are needed to address all types of populations, exposures and cognitive outcomes, particularly studies investigating environmental and occupational exposure in adults. Future studies also need to address uncertainties in the assessment of exposure and standardise testing of specific domains of cognitive function to enable synthesis across studies and increase the certainty of the evidence., Other: This review was partially funded by the WHO radioprotection programme and prospectively registered on PROSPERO CRD42021257548., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Geza Benke reports financial support was provided by World Health Organization. MA declares that he holds a small parcel of Telstra shares. KK, CB and MS as part of their employment are involved in the provision of advice to the Australian Commonwealth Government, Australian States and Territories and the general public on the risks and health effects of exposure to ionising and non-ionising radiation. KK is also a member of the International Commission on Non-Ionizing Radiation Protection where he contributes in the development and dissemination of science-based advice on limiting exposure to non-ionizing radiation. No member of the review team was involved in screening or extracting data from a study in which he or she was an author]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities., Methods and Materials: A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models., Results: The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 59.8 Gy or 63.6 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively., Conclusions: This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In this article, the impact of radiofrequency electromagnetic field (RF-EMF) exposure from a simulated base station for the 5G New Radio (5G NR) telecommunication on rats was studied. The base station affects all age groups of the population, thus, for the first time, the experiment was conducted on male Wistar rats of three different ages (juvenile, adult, and presenile). The base station exposure parameters were chosen according to ICNIRP recommendations for limiting the exposure to radiofrequency electromagnetic field: frequency 2.4 GHz with an average specific absorption rate of 0.0076 W/kg and 0.0059 W/kg over the whole body of experimental animals. Throughout the experiment, body weight was examined weekly, and the dynamics of body weight gain was monitored. Rectal and skin surface temperature on the right hind limb was monitored weekly. Testing in the Morris water maze was performed during the last, Week 5, of RF-EMF exposure. After euthanasia, organ weights were determined in experimental and control animals. None of the investigated parameters did show any statistically significant differences between exposed and control animals of the same age. The data obtained can be used to assess the possible consequences of chronic exposure to RF-EMF from 5G NR base stations., (© 2024. The Author(s).)

Purpose: Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy., Methods and Materials: In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores., Results: The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P = .03 and .007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P < .001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P < .001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores., Conclusions: Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This research article elucidates the pivotal role of radiopharmacy in the contemporary landscape, underscoring its potential therapeutic efficacy in addressing symptoms associated with aged-related neurocognitive processes. Clinical trials, characterized by the judicious application of modest radiation doses, exemplified by low-dose radon, have yielded affirmative outcomes in the amelioration of aged, related symptoms., Material and Methods: The study was conducted on an animal model. The effect of low doses of radon on cognitive processes is being studied by inhalation of randomized mineral water. Changes in the clinical picture were studied using behavioral tests, namely the Barnes maze tests. At the cellular level, radon-contained water inhalation causes different changes: in the fraction of synaptic membranes (determined by Na, K-ATPase activity), aged, related changes by telomerase activity and oxidative stress level changes., Results: Our studies show that age-related changes in brain tissue are less noticeable after radon inhalation, namely, the concentration of amyloid plaques decreases in a group of aged rats after radon therapy. A significant improvement in cognitive function was observed after radon inhalation in aged rats., Conclusion: The results show that exposure to radon-containing mineral water leads to improved spatial perception, potentially improving age-related cognitive functions not only at the level of neurocognitive tests, but also changes at the level of cellular functioning.

Background: Alzheimer's disease has become increasingly prevalent among the older population, leading to significant social and economic burdens. Transcranial photobiomodulation (tPBM) has shown promise as a cognitive intervention for enhancing cognitive efficiency in healthy older adults, and individuals with mild cognitive impairment and Alzheimer's disease. However, determining the optimal tPBM dosage is crucial for ensuring effective and efficient intervention., Objective: This study aimed to compare the effects of different dosages in a single tPBM session on cognitive efficiency in healthy older adults., Methods: In this randomized controlled trial, 88 healthy older participants were assigned to either a single dose (irradiance = 30 mW/cm2, fluence = 10.8 J/cm2; n = 44) or a double dose (irradiance = 30 mW/cm2, fluence = 21.6 J/cm2; n = 44) tPBM session. Cognitive efficiency was assessed using functional near-infrared spectroscopy during a visual working memory span task., Results: The single dose group exhibited significantly greater cognitive efficiency enhancement, indicated by a more pronounced reduction in oxygenated hemoglobin during a challenging task level (span level 9) (p = 0.021, d = 0.50), and better working memory task performance (p = 0.045, d = 0.31). Furthermore, participants with better visuospatial abilities demonstrated greater improvement after a single dose (r = -0.42, p = 0.004). In contrast, participants with varying cognitive function did not exhibit additional benefits from a double dose (r = -0.22-0.15, p = 0.16-0.95)., Conclusions: These findings suggest that higher tPBM dosages may not necessarily result in superior cognitive improvement in older adults.

Background: Radiation exposure has been linked to the development of brain damage and cognitive impairment, but the protective effect and mechanism of Lycium barbarum pills (LBP) on radiation-induced neurological damage remains to be clarified., Methods: Behavioral tests and immunohistochemical studies were conducted to evaluate the protective effects of LBP extract (10 g/kg orally daily for 4 weeks) against radiation-induced damage on neurogenesis and cognitive function in Balb/c mice exposed to 5.5 Gy X-ray acute radiation., Results: The results showed that the LBP extract significantly improved body weight loss, locomotor activity and spatial learning and memory. Immunohistochemical tests revealed that the LBP extract prevented the loss of proliferating cells, newly generated neurons and interneurons, especially in the subgranular area of the dentate gyrus., Conclusion: The findings suggest that LBP is a potential neuroprotective drug for mitigating radiation-induced neuropsychological disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

When radiotherapy is used in the treatment of head and neck cancers, the brain commonly receives incidental doses of radiotherapy with potential for neurocognitive changes and subsequent impact on quality of life. This has not been widely investigated to date. A systematic search of MEDLINE, EMBASE, Psycinfo Info and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases was conducted. Of 2077 records screened, 20 were eligible comprising 1308 patients. There were no randomised studies and 73.3% of included patients were from single center studies. IMRT was delivered in 72.6% of patients, and chemotherapy used in 61%. There was considerable heterogeneity in methods. Narrative synthesis was therefore carried out. Most studies demonstrated inferior neurocognitive outcomes when compared to control groups at 12 months and beyond radiotherapy. Commonly affected neurocognitive domains were memory and language which appeared related to radiation dose to hippocampus, temporal lobe, and cerebellum. Magnetic Resonance Imaging could be valuable in the detection of early microstructural and functional changes, which could be indicative of future neurocognitive changes. In studies investigating quality of life, the presence of neurocognitive impairment was associated with inferior quality of life outcomes. (Chemo)radiotherapy for head and neck cancer appears to be associated with a risk of long-term neurocognitive impairment. Few studies were identified, with substantial variation in methodology, thus limiting conclusions. High quality large prospective head and neck cancer studies using standardised, sensitive, and reliable neurocognitive tests are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Astronauts on exploratory missions will be exposed to particle radiation of high energy and charge (HZE particles), which have been shown to produce neurochemical and performance deficits in animal models. Exposure to HZE particles can produce both targeted effects, resulting from direct ionization of atoms along the particle track, and non-targeted effects (NTEs) in cells that are distant from the track, extending the range of potential damage beyond the site of irradiation. While recent work suggests that NTEs are primarily responsible for changes in cognitive function after HZE exposures, the relative contributions of targeted and non-targeted effects to neurochemical changes after HZE exposures are unclear. The present experiment was designed to further explore the role of targeted and non-targeted effects on HZE-induced neurochemical changes (inflammation and oxidative stress) by evaluating the effects of exposure location and particle energy/linear energy transfer (LET). Forty-six male Sprague-Dawley rats received head-only or body-only exposures to 56Fe particles [600 MeV/n (75 cGy) or 1,000 MeV/n (100 cGy)] or 48Ti particles [500 MeV/n (50 cGy) or 1,100 MeV/n (75 cGy)] or no irradiation (0 cGy). Twenty-four h after irradiation, rats were euthanized, and the brain was dissected for analysis of HZE-particle-induced neurochemical changes in the hippocampus and frontal cortex. Results showed that exposure to 56Fe and 48Ti ions produced changes in measurements of brain inflammation [glial fibrillary astrocyte protein (GFAP)], oxidative stress [NADPH-oxidoreductase-2 (NOX2)] and antioxidant enzymes [superoxide dismutase (SOD), glutathione S-transferase (GST), nuclear factor erythroid 2-related factor 2 (Nrf2)]. However, radiation effects varied depending upon the specific measurement, brain region, and exposure location. Although overall exposures of the head produced more detrimental changes in neuroinflammation and oxidative stress than exposures of the body, body-only exposures also produced changes relative to no irradiation, and the effect of particle energy/LET on neurochemical changes was minimal. Results indicate that both targeted and non-targeted effects are important contributors to neurochemical changes after head-only exposure. However, because there were no consistent neurochemical changes as a function of changes in track structure after head-only exposures, the role of direct effects on neuronal function is uncertain. Therefore, these findings, although in an animal model, suggest that NTEs should be considered in the estimation of risk to the central nervous system (CNS) and development of countermeasures., (©2023 by Radiation Research Society. All rights of reproduction in any form reserved.)

Purpose: Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year., Methods and Materials: Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L., Results: Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity., Conclusions: With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We assessed the effects of conventional and ultra-high dose rate (UHDR) electron irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Two-month-old female and male C57BL/6J mice received whole-brain conventional or UHDR irradiation. UHDR mice were irradiated with 9 MeV electrons, delivered by the Linac-based/modified beam control. The mice were irradiated or sham-irradiated at Dartmouth, the following week shipped to OHSU, and behaviorally and cognitively tested between 27 and 41 days after exposure. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage: conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percentage of Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percentage of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test. Under the experimental conditions used, cognitive injury was comparable in conventional and UHDR mice. However, the percentage of CD45+ CD11b+ Ly6+ and CD45+ CD11b+ Ly6G- cells in the hippocampus cells in the hippocampus was altered in conventional- but not UHDR-irradiated mice and the reduced percentage of Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

Purpose: Proton beam radiation therapy reduces dose to healthy brain tissue and thereby decreases the risk of treatment-related decline in neurocognition. Considering the paucity of prospective data, this study aimed to evaluate neurocognitive performance in an adult patient population with intracranial tumors., Methods and Materials: Between 2017 and 2021, patients enrolled in the MedAustron registry study and irradiated for intracranial tumors were eligible for neurocognitive assessment. Patients with available 1-year follow-up data were included in the analysis. The test battery consisted of a variety of standardized tests commonly used in European Organization for Research and Treatment of Cancer trials. Scores were transformed into z scores to account for demographic effects, and clinically relevant change was defined as a change of ≥1.5 standard deviations. Binary logistic regression analysis and the χ 2 test were conducted for clinical parameters and dosimetric hippocampal parameters to evaluate the relationship with overall cognitive decline and changes in memory., Results: One hundred twenty-three patients with mostly nonprogressive, extra-axial tumors and neurocognitive assessment at baseline and treatment end as well as 3, 6, and 12 months after completion of proton beam radiation therapy were analyzed. Overall, 7 test scores revealed stability in neurocognitive function with minimal positive changes 1 year after treatment completion (statistically significant in 6 of 7 tests), whereas the majority had no or minimal baseline deficits. At 1-year follow-up, 89.4% of all patients remained stable in their overall cognitive functioning without clinically relevant deterioration in 2 or more tests. None of them showed disease progression. Of the patients, 8.1% presented with radiation-induced brain lesions and exhibited a higher percentage of overall cognitive deterioration without reaching statistical significance. Multivariate binary logistic regression analysis revealed higher age at baseline as the only independent parameter to be associated with an overall clinically relevant cognitive decline. There was no significant correlation of hippocampal doses and memory functioning., Conclusions: One year after proton therapy, we observed preservation of cognitive functioning in the vast majority of our patients with intracranial tumors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Glioma irradiation often unavoidably damages the brain volume and affects cognition. This study aims to evaluate the relationship of remote cognitive assessments in determining cognitive impairment of irradiated glioma patients in relation to the quality of life and MRI changes., Methods: Thirty patients (16-76 aged) with two imaging (pre- and post-RT) and completed cognitive assessments were recruited. Cerebellum, right and left temporal lobes, corpus callosum, amygdala and spinal cord were delineated and their dosimetry parameters were collected. Cognitive assessments were given post-RT via telephone (Telephone Interview Cognitive Status (TICS), Telephone Montreal Cognitive Assessment (T-MoCA), Telephone Mini Addenbrooke's Cognitive Examination (Tele-MACE)). Regression models and deep neural network (DNN) were used to evaluate the relationship between brain volume, cognition and treatment dose in patients., Results: Cognitive assessments were highly inter-correlated (r > 0.9) and impairment was shown between pre- and post-RT findings. Brain volume atrophy was shown post-RT, and cognitive impairments were correlated with radiotherapy-associated volume atrophy and dose-dependent in the left temporal lobe, corpus callosum, cerebellum and amygdala. DNN showed a good area under the curve for cognitive prediction; TICS (0.952), T-MoCA (0.909) and Tele-MACE (0.822)., Conclusions: Cognition can be evaluated remotely in which radiotherapy-related brain injury is dose-dependent and volume-dependent. Prediction models can assist in the early identification of patients at risk for neurocognitive decline following RT for glioma, thus facilitating potential treatment interventions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Pediatric patients with craniopharyngioma risk cognitive deficits when treated with radiation therapy. We investigated cognitive outcomes after conformal photon radiation therapy (CRT) and the effect of visual deficits and hormone deficiencies., Methods and Materials: One hundred one pediatric patients were enrolled on a single institutional protocol beginning in 1998 (n = 76) or followed a similar nonprotocol treatment plan (n = 25). CRT (54 Gy) was administered using a 1.0- or 0.5-cm clinical target volume margin. Median age at CRT was 9.50 years (range, 3.20-17.63 years). Patients were followed for 10 years with assessment of hearing, vision, hormone deficiencies, and cognitive performance., Results: Intellectual functioning (intelligence quotient) was significantly lower in children treated at a younger age and those who received higher doses to temporal lobes and hippocampi. Black race (-17.77 points, P = .002) and cerebrospinal fluid shunting (-11.52 points, P = .0068) were associated with lower baseline intelligence quotient. Reading scores were lower over time in models incorporating age, shunt, and dose to specific brain structures. Patients treated for growth hormone deficiency within 12 months of CRT had better intelligence and attention outcomes. Among patients with normal baseline vision, the 10-year cumulative incidence of change in visual acuity was 4.00% ± 2.82% and in visual field 10.42% ± 4.48%. Reading scores decreased after treatment (0.7873 points/y, P = .0451) in those with impaired baseline vision., Conclusions: Cognitive outcomes are selectively affected by dose to brain subvolumes, comorbidities of visual deficits, and treatment of endocrinopathy in pediatric craniopharyngioma. Improved treatment selection, normal tissue sparing methods of irradiation, and posttreatment management of endocrinopathy should be considered., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Health hazards from long-term exposure to microwaves, especially the potential for changes in cognitive function, are attracting increasing attention. The purpose of this study was to explore changes in spatial learning and memory and synaptic structure and to identify differentially expressed proteins in hippocampal and serum exosomes after long-term exposure to 2.856 and 9.375 GHz microwaves. The spatial reference learning and memory abilities and the structure of the DG area were impaired after long-term exposure to 2.856 and 9.375 GHz microwaves. We also found a decrease in SNARE-associated protein Snapin and an increase in charged multivesicular body protein 3 in the hippocampus, indicating that synaptic vesicle recycling was inhibited and consistent with the large increase in presynaptic vesicles. Moreover, we investigated changes in serum exosomes after 2.856 and 9.375 GHz microwave exposure. The results showed that long-term 2.856 GHz microwave exposure could induce a decrease in calcineurin subunit B type 1 and cytochrome b-245 heavy chain in serum exosomes. While the 9.375 GHz long-term microwave exposure induced a decrease in proteins (synaptophysin-like 1, ankyrin repeat and rabankyrin-5, protein phosphatase 3 catalytic subunit alpha and sodium-dependent phosphate transporter 1) in serum exosomes. In summary, long-term microwave exposure could lead to different degrees of spatial learning and memory impairment, EEG disturbance, structural damage to the hippocampus, and differential expression of hippocampal tissue and serum exosomes., (© 2023. The Author(s).)

Objective: Approximately 50-90% of brain metastatic patients who receive radiation therapy (RT) exhibit cognitive decline which may affects the quality of life of cancer survivors. Hence preservation of cognitive functions in brain metastatic patients becomes important. This review aims to evaluates the pathology or mechanism of cognitive function impairment after brain irradiation and strategies available to preserve cognitive function after radiation therapy., Data Sources: Published articles evaluating the pathology behind radiation induced cognitive impairment and strategies to resolve or preserve cognitive impairment were searched for in scientific databases (eg: PubMed, Scopus, Cochrane database, Google scholar) using keywords including memantine, brain metastases, radiation therapy, pathophysiology, pathogenesis, mechanism and prevention., Data Summary: Several hypotheses have been offered to explain the mechanism of radiation induced cognitive decline. Among them, vascular hypotheses play a significant role. Some pharmacological agents have been also tested in patients receiving radiotherapy, memantine was found beneficial based with the reference to existing data., Conclusion: Future studies are required to evaluate the impact of memantine in different types of radiation therapy procedures and its effects on quality of life of brain metastatic survivors.

The aim of the study was to establish the dependence of memory processes and learning ability in gamma-irradiated white mice on the age and period after irradiation. The 3-month and 1-year-old male mice (Mus musculus) were used in the study. Mice whole-body irradiation was performed at a dose of 5 Gy with 137Cs by using a "Gamma-capsule-2". Spatial learning and formation of memory were estimated in the elevated-type multi-way maze and elevated plus-maze. Experiments were carried out 48 hours and 30 days after irradiation for seven days (five trials each day). The number of errors (deviations from optimal trajectory) and total time for crossing the maze were calculated. The results of the study indicate that ionizing irradiation with a total dose of 5 Gy results in a delayed spatial learning process, causes spatial memory and behavior changes in different age groups of animals - aged mice turned out to be more radio-resistant. Age-related radio-resistance plays an especially major role in the early stage of post-radiation recovery. Though, the late radiation aging effect is especially pronounced in young animals.

Purpose: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities., Methods and Materials: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with 18 F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation., Results: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation., Conclusions: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Pupillometry has become a standard measure for assessing arousal state. However, environmental factors such as luminance, a primary dictator of pupillary responses, often vary across studies. To what degree does luminance interact with arousal-driven pupillary changes? Here, we parametrically assessed luminance-driven pupillary responses across a wide-range of luminances, while concurrently manipulating cognitive arousal using auditory math problems of varying difficulty. At the group-level, our results revealed that the modulatory effect of cognitive arousal on pupil size interacts multiplicatively with luminance, with the largest effects occurring at low and mid-luminances. However, at the level of individuals, there were qualitatively distinct individual differences in the modulatory effect of cognitive arousal on luminance-driven pupillary responses. Our findings suggest that pupillometry as a measure for assessing arousal requires more careful consideration: there are ranges of luminance levels that are more ideal in observing pupillary differences between arousal conditions than others., (© 2022. The Author(s).)

Purpose: To characterize the association between neurocognitive outcomes (memory and processing speed) and radiation (RT) dose to the hippocampus, corpus callosum (CC), and frontal white matter (WM) in children with medulloblastoma treated on a prospective study, SJMB03., Patients and Methods: Patients age 3-21 years with medulloblastoma were treated at a single institution on a phase III study. The craniospinal RT dose was 23.4 Gy for average-risk patients and 36-39.6 Gy for high-risk patients. The boost dose was 55.8 Gy to the tumor bed. Patients underwent cognitive testing at baseline and once yearly for 5 years. Performance on tests of memory (associative memory and working memory) and processing speed (composite processing speed and perceptual speed) was analyzed. Mixed-effects models were used to estimate longitudinal trends in neurocognitive outcomes. Reliable change index and logistic regression were used to define clinically meaningful neurocognitive decline and identify variables associated with decline., Results: One hundred and twenty-four patients were eligible for inclusion, with a median neurocognitive follow-up of 5 years. Mean right and left hippocampal doses were significantly associated with decline in associative memory in patients without posterior fossa syndrome (all P < .05). Mean CC and frontal WM doses were significantly associated with decline in both measures of processing speed (all P < .05). Median brain substructure dose-volume histograms were shifted to the right for patients with a decline in associative memory or processing speed. The odds of decline in associative memory and composite processing speed increased by 23%-26% and by 10%-15% for every 1-Gy increase in mean hippocampal dose and mean CC or frontal WM dose, respectively., Conclusion: Increasing RT dose to the CC or frontal WM and hippocampus is associated with worse performance on tests of processing speed and associative memory, respectively. Brain substructure-informed RT planning may mitigate neurocognitive impairment., Competing Interests: Lydia WilsonHonoraria: Elekta Amar GajjarConsulting or Advisory Role: Roche/Genentech, QED Therapeutics, Day One TherapeuticsResearch Funding: Genentech (Inst), Kazia Therapeutics (Inst) Thomas E. MerchantHonoraria: Varian Medical SystemsTravel, Accommodations, Expenses: Philips HealthcareNo other potential conflicts of interest were reported.

Background: Proton therapy may reduce cognitive deficits after radiotherapy among brain tumor survivors, although current data are limited to retrospective comparisons between historical cohorts. The authors compared intelligence quotient scores within a case-matched cohort of children with medulloblastoma treated with proton radiation (PRT) or photon radiation (XRT) over the same time period., Methods: Among 88 consecutive patients with standard-risk medulloblastoma treated with PRT or XRT at 2 institutions from 2000 to 2009, 50 were matched 1:1 (25 with PRT and 25 with XRT) according to age, gender, date of diagnosis, histology, radiation boost, and craniospinal irradiation dose. One-way analyses of variance were performed to compare the Full-Scale Intelligence Quotient (FSIQ) and associated index scores between the 2 cohorts., Results: Neurocognitive data were available for 37 survivors (17 with PRT and 20 with XRT) from the matched cohort. The mean age was 8.5 years (SD, 4.14 years). The median follow-up was 5.3 years (range, 1.0-11.4 years) and 4.6 years (range, 1.1-11.2 years) for the PRT and XRT cohorts, respectively (P = .193). Patients treated with PRT had significantly higher mean FSIQ (99.6 vs 86.2; P = .021), verbal (105.2 vs 88.6; P = .010), and nonverbal scores (103.1 vs 88.9; P = .011) than the XRT-treated cohort. Differences in processing speed (82.9 vs 77.2; P = .331) and working memory (97.0 vs 92.7; P = .388) were not statistically significant., Conclusions: Radiotherapy-associated cognitive effects appear to be more attenuated after proton therapy. Comprehensive prospective studies are needed to appropriately evaluate the neurocognitive advantages of proton therapy., (© 2021 American Cancer Society.)

Purpose: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone., Methods: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI., Results: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different., Conclusion: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI., Competing Interests: Núria Rodríguez de DiosConsulting or Advisory Role: AstraZeneca SpainSpeakers' Bureau: AstraZeneca Spain, Siemens Healthineers Felipe CouñagoHonoraria: AstraZeneca, Astellas Pharma Juan Domigo GispertResearch Funding: Roche Diagnostics, GE Healthcare Jaume CapelladesTravel, Accommodations, Expenses: MedtronicNo other potential conflicts of interest were reported.

Radiation exposure has multiple effects on the brain, behavior and cognitive functions. It has been reported that high-dose (>20 Gy) radiation-induced behavior and cognitive aberration partly associated with severe tissue destruction. Low-dose (<3 Gy) exposure can occur in radiological disasters and cerebral endovascular treatment. However, only a few reports analyzed behavior and cognitive functions after low-dose irradiation. This study was undertaken to assess the relationship between brain neurochemistry and behavioral disruption in irradiated mice. The irradiated mice (0.5 Gy, 1 Gy and 3 Gy) were tested for alteration in their normal behavior over 10 days. A serotonin (5-HT), Dopamine, gamma-Aminobutyric acid (GABA) and cortisol analysis was carried out in blood, hippocampus, amygdala and whole brain tissue. There was a significant decline in the exploratory activity of mice exposed to 3 Gy and 1 Gy radiation in an open field test. We observed a significant short-term memory loss in 3 Gy and 1 Gy irradiated mice in Y-Maze. Mice exposed to 1 Gy and 3 Gy radiation exhibited increased anxiety in an elevated plus maze (EPM). The increased anxiety and memory loss patterns were also seen in 0.5 Gy irradiated mice, but the results were not statistically significant. In this study we observed that neurotransmitters are significantly altered after irradiation, but the neuronal cells in the hippocampus were not significantly affected. This study suggests that the low-dose radiation-induced cognitive impairment may be associated with the neurochemical in low-dose irradiation and unlike the high-dose scenario might not be directly related to the morphological changes in the brain., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Currently, the impact of electromagnetic field (EMF) exposure on the nervous system is an increasingly arousing public concern. The present study was designed to explore the effects of continuous long-term exposure to L-band high-power microwave (L-HPM) on brain function and related mechanisms. Forty-eight male Institute of Cancer Research (ICR) mice were exposed to L-HPM at various power densities (0.5, 1.0, and 1.5 W/m 2 ) and the brain function was examined at different time periods after exposure. The morphology of the brain was examined by hematoxylin-eosin (HE) and deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, cholinergic markers, oxidative stress markers, and the expression of c-fos were evaluated to identify a "potential" mechanism. The results showed that exposure to L-HPM at 1.5 W/m 2 can cause generalized injuries in the hippocampus (CA1 and CA3) and cerebral cortex (the first somatosensory cortex) of mice, including cell apoptosis, cholinergic dysfunction, and oxidative damage. Moreover, the deleterious effects were closely related to the power density and exposure time, indicating that long-term and high-power density exposure may be detrimental to the nervous system., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Yanyun Lin et al.)

Purpose: The purpose of this critical review is to summarize the literature specific to single-fraction stereotactic radiosurgery (SRS) and multiple-fraction stereotactic radiation therapy (SRT) for postoperative brain metastases resection cavities and to present practice recommendations on behalf of the ISRS., Methods and Materials: The Medline and Embase databases were used to apply the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach to search for manuscripts reporting SRS/SRT outcomes for postoperative brain metastases tumor bed resection cavities with a search end date of July 20, 2018. Prospective studies, consensus guidelines, and retrospective series that included exclusively postoperative brain metastases and had at minimum 100 patients were considered eligible., Results: The Embase search revealed 157 manuscripts, of which 77 were selected for full-text screening. PubMed yielded 55 manuscripts, of which 23 were selected for full text screening. We deemed 8 retrospective series, 1 phase 2 prospective study, 3 randomized controlled trials, and 1 consensus contouring paper appropriate for inclusion. The data suggest that SRS/SRT to surgical cavities with prescription doses of 30 to 50 Gy equivalent effective dose (EQD) 2 10 , 50 to 70 Gy EQD2 5 , and 70 to 90 EQD2 2 are associated with rates of local control ranging from 60.5% to 91% (median, 80.5%). Randomized data suggest improved local control with single-fraction SRS compared with observation and improved cognitive outcomes compared with whole-brain radiation therapy (WBRT). The toxicity of SRS/SRT in the postoperative setting was limited and is reviewed herein., Conclusions: Although randomized data raise concern for poorer local control after resection cavity SRS than WBRT, these findings may be driven by factors such as conservative prescription doses used in the SRS arm. Retrospective studies suggest high rates of local control after single-fraction SRS and hypofractionated SRT for postoperative brain metastases. With a superior neurocognitive profile and no survival disadvantage to withholding WBRT, the ISRS recommends SRS as first-line treatment for eligible postoperative patients. Emerging data suggest that fractionated SRT may provide superior local control compared with single-fraction SRS, in particular, for large tumor cavity volumes/diameters and potentially for patients with a preoperative diameter greater than 2.5 cm., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous research revealed inconsistent effects of bright light or a short nap at noon on alertness and performance across different tasks. The current study aimed to explore whether the effects of bright light and a short nap at noon on task performance depended on the cognitive domain. Bright light (1,200 lx, 4,000 K at eye level), nap (near darkness) and control (200 lx, 4,000 K at eye level) conditions were performed from 1:00 to 1:40 PM on three non-consecutive days with a counterbalanced order across participants. After being assigned to one of three conditions, participants underwent two repeated test sessions, each including a psychomotor vigilance task, a go/no-go task, and a paced visual serial addition task, with an interval of more than 1 h, to assess the persistent effects of napping and bright light. Subjective sleepiness, vitality, self-control and mood were also measured. Results showed that accuracy on the go/no-go task and the paced visual serial addition task improved significantly throughout the entire experiment session after napping, whereas reaction speed on the paced visual serial addition task improved time-dependently in the bright light intervention, with a higher reaction speed in only the first test session. Nearly all subjective states benefited from napping but not from bright light. These findings suggested that the effects of bright light and an afternoon nap on task performance would depend on the cognitive domain. An afternoon nap may elicit more effective and persistent benefits on task performance and subjective states., (© 2020 European Sleep Research Society.)

Purpose: Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine ( 18 F-DOPA) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using 18 F-DOPA PET in patients with glioblastoma., Methods and Materials: Patients with newly diagnosed, histologically confirmed glioblastoma aged ≥18 years without contraindications to 18 F-DOPA were eligible. Target volumes included 51, 60, and 76 Gy in 30 fractions with a simultaneous integrated boost, and concurrent and adjuvant temozolomide for 6 months. 18 F-DOPA PET imaging was used to guide DERT. The study was designed to detect a true progression-free survival (PFS) at 6 months (PFS6) rate ≥72.5% in O6-methylguanine methyltransferase (MGMT) unmethylated patients (DE-Un), with an overall significance level (alpha) of 0.20 and a power of 80%. Kaplan-Meier analysis was performed for PFS and overall survival (OS). Historical controls (HCs) included 139 patients (82 unmethylated) treated on prospective clinical trials or with standard RT at our institution. Toxicities were evaluated with Common Terminology Criteria for Adverse Events v4.0., Results: Between January 2014 and December 2018, 75 evaluable patients were enrolled (39 DE-Un, 24 methylated [DE-Mth], and 12 indeterminate). PFS6 for DE-Un was 79.5% (95% confidence interval, 63.1%-90.1%). Median PFS was longer for DE-Un patients compared with historical controls (8.7 months vs 6.6 months; P = .017). OS was similarly longer, but the difference was not significant (16.0 vs 13.5 months; P = .13). OS was significantly improved for DE-Mth patients compared with HC-Mth (35.5 vs 23.3 months; P = .049) despite nonsignificant improvement in PFS (10.7 vs 9.0 months; P = .26). Grade 3 central nervous system necrosis occurred in 13% of patients, but treatment with bevacizumab improved symptoms in all cases., Conclusions: 18 F-DOPA PET-guided DERT appears to be safe, and it significantly improves PFS in MGMT unmethylated glioblastoma. OS is significantly improved in MGMT methylated patients. Further investigation of 18 F-DOPA PET biologic guided DERT for glioblastoma is warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The space radiation environment consists of multiple species of charged particles, including 28 Si ions, that may impact brain function during and following missions. To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28 Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. The plasma of the mice was collected for analysis of miRNA levels. Select pertinent brain regions were dissected for lipidomic analyses and analyses of levels of select biomarkers shown to be sensitive to effects of space radiation in previous studies. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28 Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Levels of the dendritic marker MAP2 in the cortex were higher in irradiated than sham-irradiated mice at middle age, which might be part of a compensatory response. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28 Si ion irradiation could be used for the development of biomarker of the space radiation response., (© 2021. The Author(s).)

Exposure of rodents to <20 cGy Space Radiation (SR) impairs performance in several hippocampus-dependent cognitive tasks, including spatial memory. However, there is considerable inter-individual susceptibility to develop SR-induced spatial memory impairment. In this study, a robust label-free mass spectrometry (MS)-based unbiased proteomic profiling approach was used to characterize the composition of the hippocampal proteome in adult male Wistar rats exposed to 15 cGy of 1 GeV/n 48 Ti and their sham counterparts. Unique protein signatures were identified in the hippocampal proteome of: (1) sham rats, (2) Ti-exposed rats, (3) Ti-exposed rats that had sham-like spatial memory performance, and (4) Ti-exposed rats that impaired spatial memory performance. Approximately 14% (159) of the proteins detected in hippocampal proteome of sham rats were not detected in the Ti-exposed rats. We explored the possibility that the loss of the Sham-only proteins may arise as a result of SR-induced changes in protein homeostasis. SR-exposure was associated with a switch towards increased pro-ubiquitination proteins from that seen in Sham. These data suggest that the role of the ubiquitin-proteome system as a determinant of SR-induced neurocognitive deficits needs to be more thoroughly investigated.

During space missions, astronauts experience acute and chronic low-dose-rate radiation exposures. Given the clear gap of knowledge regarding such exposures, we assessed the effects acute and chronic exposure to a mixed field of neutrons and photons and single or fractionated simulated galactic cosmic ray exposure (GCRsim) on behavioral and cognitive performance in mice. In addition, we assessed the effects of an aspirin-containing diet in the presence and absence of chronic exposure to a mixed field of neutrons and photons. In C3H male mice, there were effects of acute radiation exposure on activity levels in the open field containing objects. In addition, there were radiation-aspirin interactions for effects of chronic radiation exposure on activity levels and measures of anxiety in the open field, and on activity levels in the open field containing objects. There were also detrimental effects of aspirin and chronic radiation exposure on the ability of mice to distinguish the familiar and novel object. Finally, there were effects of acute GCRsim on activity levels in the open field containing objects. Activity levels were lower in GCRsim than sham-irradiated mice. Thus, acute and chronic irradiation to a mixture of neutrons and photons and acute and fractionated GCRsim have differential effects on behavioral and cognitive performance of C3H mice. Within the limitations of our study design, aspirin does not appear to be a suitable countermeasure for effects of chronic exposure to space radiation on cognitive performance., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Heat exposure affects several physiological, neuronal, and emotional functions. Notably, monoaminergic neurotransmitters in the brain such as noradrenaline, dopamine, and serotonin, which regulate several basic physiological functions, such as thermoregulation, food intake, and energy balance, are affected by heat exposure and heat acclimation. Furthermore, cognition and emotional states are also affected by heat exposure and changes in brain monoamine levels. Short-term heat exposure has been reported to increase anxiety in some behavioral tests. In contrast, there is a possibility that long-term heat exposure decreases anxiety due to heat acclimation. These changes might be due to adaptation of the core body temperature and/or brain monoamine levels by heat exposure. In this review, we first outline the changes in brain monoamine levels and thereafter focus on changes in emotional behavior due to heat exposure and heat acclimation. Finally, we describe the relationships between emotional behavior and brain monoamine levels during heat acclimation., (Copyright © 2021. Published by Elsevier Ltd.)

Shift workers are mostly suffered from the disruption of circadian rhythm and health problems. In this study, we designed proper light environment to maintain stable circadian rhythm, cognitive performance, and mood status of shift workers. We used five-channel light-emitting diodes to build up the dynamic daylight-like light environment. The illuminance, correlated color temperature, and circadian action factor of light were tunable in the ranges of 226 to 678 lx, 2680 to 7314 K, and 0.32 to 0.96 throughout the day (5:30 to 19:40). During the nighttime, these parameters maintained about 200 lx, 2700 K, and 0.32, respectively. In this light environment, three subjects had engaged in shift work for 38 consecutive days. We measured plasma melatonin, activity counts, continuous performance tests, and visual analogue scale on mood to assess the rhythm, cognitive performance, and mood of subjects. After 38-day shift work, the subjects' peak melatonin concentration increased significantly. Their physiological and behavioral rhythms maintained stable. Their cognitive performance improved significantly after night work, compared with that before night work. Their mood status had no significant change during the 38-day shift work. These results indicated that the light environment was beneficial to maintain circadian rhythm, cognitive performance and mood status during long-term shift work in closed environment.

Purpose: The corpus callosum (CC) and intrahemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention and processing speed performance before and after radiation therapy in primary brain tumor patients., Methods and Materials: In a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and magnetic resonance imaging/diffusion-weighted imaging at baseline (pre-radiation therapy) and 3-, 6-, and 12-months post-radiation therapy. CC (subregions, total) and IHWM tracts (left/right without CC, total) were autosegmented; tumor, tumor bed, and edema were censored. Biomarkers included volume changes (cm 3 ), mean diffusivity ([MD]; higher values indicate white matter injury), fractional anisotropy ([FA]; lower values indicate white matter injury). Reliable-change indices measured changes in attention (Weschler Adult Intelligence Scale [WAIS-IV] digits-forward; Delis-Kaplan Executive Function System Trail Making [D-KEFS-TM] visual-scanning), and processing speed (WAIS-IV coding; D-KEFS-TM number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between mean radiation dose and biomarkers (volume, MD, FA) and imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons., Results: Processing speed declined at 6 months following radiation therapy (number sequencing, letter sequencing; P < .04). Seizures and antiepileptic drug therapy were associated with lower visual-scanning attention reliable-change indices at 6 months (P = .039). Higher radiation dose correlated with smaller midanterior CC volume (P = .023); lower FA in posterior CC, anterior CC, and total CC (all P < .03); and higher MD in anterior CC (P = .012). Smaller midanterior CC and left IHWM volume correlated with worse processing speed (coding, letter-sequencing, number-sequencing; all P < .03). Higher FA in right, left, and total IHWM correlated with better coding scores (all P < .01). Lower FA in total IHWM (P = .009) was associated with worse visual-scanning attention scores. Higher FA in midposterior CC (P = .029) correlated with better digits-forward attention scores., Conclusions: The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention and processing speed decline after radiation therapy. These areas represent possible avoidance regions for preservation of attention and processing speed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Conflicting results have been reported regarding the effectiveness of light treatment (LT) in patients with Alzheimer's disease (AD). We investigated the effectiveness of blue-enriched white LT on sleep, cognition, mood and behavior in patients with mild and moderate AD. The treatment group (n = 14) sat about 60 cm away from a small (136 × 73 × 16 mm) LED light box for 1 h each morning for 2 weeks. The control group (n = 11) wore dark, blue-attenuating sunglasses during the 1 h exposures. The morning light started 9-10 h after each individual's dim light melatonin onset (DLMO). Assessments were done at baseline (T0), immediate post-treatment (T1), and 4 weeks after the end of the 2 weeks of LT (T2). Sleep was measured by actigraphy. Blue-enriched LT had a significantly better effect on the Pittsburgh Sleep Quality Index at T2 compared to blue-attenuated LT, and a trend of better effectiveness on total sleep time at T2. There was a significant increase in Mini-Mental State Examination score at T2 after blue-enriched LT than that at T0. Our findings suggest that morning blue-enriched LT has a benefit in improving sleep and cognitive function in AD patients.

We examined whether dynamically changing light across a scheduled 16-h waking day influences sleepiness, cognitive performance, visual comfort, melatonin secretion, and sleep under controlled laboratory conditions in healthy men. Fourteen participants underwent a 49-h laboratory protocol in a repeated-measures study design. They spent the first 5 hours in the evening under standard lighting, followed by an 8-h nocturnal sleep episode at habitual bedtimes. Thereafter, volunteers either woke up to static light or to a dynamic light that changed spectrum and intensity across the scheduled 16-h waking day. Following an 8-h nocturnal sleep episode, the volunteers spent another 11 hours either under static or dynamic light. Static light attenuated the evening rise in melatonin levels more compared to dynamic light as indexed by a significant reduction in the melatonin AUC prior to bedtime during static light only. Participants felt less vigilant in the evening during dynamic light. After dynamic light, sleep latency was significantly shorter in both the baseline and treatment night while sleep structure, sleep quality, cognitive performance, and visual comfort did not significantly differ. The study shows that dynamic changes in spectrum and intensity of light promote melatonin secretion and sleep initiation in healthy men., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A cohort of children prenatally exposed to the 1945 atomic bombings in Japan revealed harmful effects of ionizing radiation in a variety of measures of cognitive function, including mental retardation. Here we examined cognitive function in the non-affected, now elderly, cohort., Methods: From 2011-2015, using the Cognitive Abilities Screening Instrument and a maternal uterine radiation dose estimated with the 2002 dosimetry system, we evaluated 303 prenatally exposed subjects and their non-exposed controls from the Adult Health Study of the Radiation Effects Research Foundation, excluding those who had shown marked cognitive effects earlier. About 11% of the subjects were exposed to more than 250 mGy. We examined a self-reported disease history and, using regression analysis, evaluated the relationship between cognitive function and radiation exposures, adjusting for demographic factors., Results: None of the subjects reported a history of dementia. We also did not find a significant radiation effect on cognitive function overall or in any gestational-week group. Education was associated with a significant effect, but educational level was not associated with radiation dose., Conclusion: We found no significant radiation effect on cognitive function among 65- to 70-year-old subjects who were prenatally exposed to the bombings and did not have marked childhood cognitive function deterioration. The limitations of this study include a small sample size and potential bias pertaining to non-participation in the Adult Health Study or refusal of Cognitive Abilities Screening Instrument evaluation. Further investigations using various endpoints in other populations prenatally exposed to radiation are warranted., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ultrasound-(US) emitting sources are highly present in modern human environments (e.g., movement sensors, electric transformers). US affecting humans or even posing a health hazard remains understudied. Hence, ultrasonic (22.4 kHz) vs. sham devices were installed in participants' bedrooms, and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, executive function, and structural MRI were assessed pre-post. Somatization (possible nocebo) and phasic alertness increased significantly in sham, accuracy in a flexibility task decreased significantly in the verum condition (indicating hastier responses). Effects were not sustained after p-level adjustment. Exploratory voxel-based morphometry (VBM) revealed regional grey matter (rGMV) but no regional white matter volume changes in verum (relative to placebo). rGMV increased in bilateral cerebellum VIIb/Crus II and anterior cingulate (BA24). There were rGMV decreases in two bilateral frontal clusters: in the middle frontal gyri/opercular part of inferior frontal gyrus (BA46, 44), and the superior frontal gyri (BA4 ,6, 8). No brain-behavior-links were identified. Given the overall pattern of results, it is suggested that ultrasound may particularly induce regional gray matter decline in frontal areas, however with yet unclear behavioral consequences. Given the localization of clusters, candidate behavioral variables for follow-up investigation are complex motor control/coordination, stress regulation, speech processing, and inhibition tasks.Trial registration: The trial was registered at NIH www.clinicaltrials.gov , trial identifier: NCT03459183, trial name: SonicBrain01, full trial protocol available here: https://clinicaltrials.gov/ct2/show/NCT03459183 .

People often encounter various sources of ionizing radiation, both in modern medicine and under various environmental conditions, such as space travel, nuclear power plants or in conditions of man-made disasters that may lead to long-term cognitive impairment. Whilst the effect of exposure to low and high doses of gamma and X-radiation on the central nervous system (CNS) has been well investigated, the consequences of protons and heavy ions irradiation are quite different and poorly understood. As for the assessment of long-term effects of carbon ions on cognitive abilities and neurodegeneration, very few data appeared in the literature. The main object of the research is to investigate the effects of accelerated carbon ions on the cognitive function. Experiments were performed on male SHK mice at an age of two months. Mice were irradiated with a dose of 0.7 Gy of accelerated carbon ions with an energy of 450 meV/n in spread-out Bragg peak (SOBP) on a U-70 particle accelerator (Protvino, Russia). Two months after the irradiation, mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. One month after the evaluation of cognitive activity, histological analysis of dorsal hippocampus was carried out to assess its morphological state and to reveal late neuronal degeneration. It was found that the mice irradiated with accelerated carbon ions develop an altered behavioral pattern characterized by anxiety and a shortage in hippocampal-dependent memory retention, but not in episodic memory. Nissl staining revealed a reduction in the number of cells in the dorsal hippocampus of irradiated mice, with the most pronounced reduction in cell density observed in the dentate gyrus (DG) hilus. Also, the length of the CA3 field of the dorsal hippocampus was significantly reduced, and the number of cells in it was moderately decreased. Experiments with the use of Fluoro-Jade B (FJB) staining revealed no FJB-positive regions in the dorsal hippocampus of irradiated and control animals 3 months after the irradiation. Thus, no morbid cells were detected in irradiated and control groups. The results obtained indicate that total irradiation with a low dose of carbon ions can produce a cognitive deficit in adult mice without evidence of neurodegenerative pathologic changes.

Adult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.

Associative memory (AM) reflects the ability to remember and retrieve multiple pieces of information bound together thus enabling complex episodic experiences. Despite growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of AM, there are inconsistent evidence regarding its benefits. An alternative to standard constant tDCS could be the application of frequency-modulated tDCS protocols, that mimic natural function-relevant brain rhythms. Here, we show the effects of anodal tDCS oscillating in theta rhythm (5 Hz; 1.5 ± 0.1 mA) versus constant anodal tDCS and sham over left posterior parietal cortex on cued recall of face-word associations. In a crossover design, each participant completed AM assessment immediately following 20-min theta-oscillatory, constant, and sham tDCS, as well as 1 and 5 days after. Theta oscillatory tDCS increased initial AM performance in comparison to sham, and so did constant tDCS. On the group level, no differences between oscillatory and constant tDCS were observed, but individual-level analysis revealed that some participants responded to theta-oscillatory but not to constant tDCS, and vice versa, which could be attributed to their different physiological modes of action. This study shows the potential of oscillatory tDCS protocols for memory enhancement to produce strong and reliable memory-modulating effects which deserve to be investigated further.

Space is an isolated, confined environment for humans. These conditions can have numerous effects on astronaut mental health and safety. Psychological and social issues affect space crew due to the isolation, confinement, and prolonged separation from family and friends. This area of research is particularly crucial given the space sector's plans for Martian colonies and space tourism, as well as to aid astronauts when under high stress. Therefore, this paper reviews the effects of isolation/confinement on psychological and cognitive health; impact of radiation and microgravity on cognitive health; and implications of disturbances to the circadian rhythm and sleep in space. Possible solutions to relevant mentioned cognitive and mental health challenges are also discussed., (Copyright © 2020. Published by Elsevier B.V.)

Microglia are the resident immune cells of the central nervous system (CNS). In physiological conditions, microglia contribute to maintaining brain homeostasis by scanning the surrounding parenchyma and acting as scavenger cells. Following different insults to the CNS, microglia turn into a "reactive" state characterized by the production of inflammatory mediators that promote tissue repair to restore homeostasis. Brain insults such as traumatic brain injury, therapeutic brain irradiation and galactic cosmic ray exposure are associated with chronic microglia activation. Chronic microglia activation contributes to injury-related impairments in cognitive functions. Microglia depletion achieved either by pharmacological or genetic techniques represents not only a useful tool for more extensive investigations of microglia roles, but also a potential therapeutic approach to ameliorate or prevent cognitive dysfunctions following brain injury., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Recent studies of photobiomodulation (PBM) in patients with cognitive or psychological disorders (including traumatic brain injury, stroke, and dementia) have yielded some encouraging results., Objective: In this study, we aimed to investigate the effect of a single stimulation on memory in older adults with mild cognitive impairment (MCI)., Methods: After PBM, hemodynamic changes, as a measure of functional brain activity, were evaluated using functional near-infrared spectroscopy (fNIRS). Eighteen subjects who met the criteria of MCI were randomly assigned to control and experimental groups. A single real or sham PBM session was administered to the forehead of each patient in the experimental and control groups, respectively. All subjects performed a visual memory span test before and after the stimulation, and their hemodynamic responses during the tasks were measured using fNIRS., Results: The results showed that among the MCI subjects, only those who received PBM, but not those who received the sham stimulation, demonstrated significant improvement in the visual memory performance and a reduction in the hemodynamic response during the tasks., Conclusion: These findings suggest that PBM may reduce the cognitive efforts needed to complete tasks that require high memory loads, and thus improve the cognitive performance of individuals with MCI.

Objective: Neurocognitive functioning (NCF) is an important component of quality of life (QoL) in glioma patients. The neurocognitive toxicity from irradiation of brain tumours may be related to damage to neural progenitor cells (NPC). The aim of our study was to assess the NCF in illiterate glioma patients., Methods: This was a prospective study done in glioma patients admitted for adjuvant treatment. Illiterate and semiliterate post op glioma patients with ECOG PS ≤ 3 were included. Neurocognitive assessment was done using Addenbrooke's Cognitive Examination (ACE-III) questionnaire prior to the start of RT and at 6month and 12 month follow up. The scores were correlated to the doses to sub ventricular zone (SVZ) and sub granular zone (SGZ) regions., Results: 20 patients were recruited.16 patients were illiterate and four patients were semiliterate. Median of the mean dose to the SVZ I/L (ipsilateral) was 48.5 Gy and SGZ I/L was 39.5 Gy. In patients who received ≤49 Gy mean dose to SVZ I/L, there was statistically significant improvement in memory, fluency, language and total ACE scores at six months. In patients with SGZ I/L mean dose ≤40 Gy, there was improvement in memory, language, and total ACE score at six months. Similar trend continued at 12 months follow up., Conclusions: NCF assessment by ACE III questionnaire is a useful tool even in illiterate patients. Lower RT doses to the ipsilateral SVZ and SGZ showed significant improvement in total ACE scores at 6 months and improvement in specific domains at 6 and 12 months., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated., Objective: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function., Methods: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM., Results: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function., Conclusion: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.

Although the key scene of the hippocampus in memory processes is obvious, the specificity of its participation in information processing is far from being established. Current advanced neuroimaging enables to operate with precise morphometric parameters. The aim of the study was to reveal fine memory rearrangements under mechanical impact on the hippocampus by a neoplasm and radiation exposure in the course of therapy., Materials and Methods: We used a homogeneous sample of 28 patients with parasellar meningiomas adjacent to hippocampus. In 10 patients (5 with left-sided and 5 with right-sided meningiomas), the tumor was located near the hippocampus but exhibited no mechanical effect on it. In 18 patients (10 with left-sided and 8 with right-sided tumors), the neoplasm compressed the adjacent hippocampus. The control group consisted of 39 healthy subjects. All three groups were comparable in age, education, and gender characteristics. In order to control tumor growth, the patients underwent radiotherapy when the hippocampus involuntary was exposed to a dose comparable to that in the tumor (30 sessions with a single focal dose of 1.8 Gy, total dose - 54.0 Gy).Based on the literature data on hippocampus involved in mnestic processes, a special methodology to investigate memory was developed. Incorrect responses the subjects made when identifying previously memorized images were classified as neutralizing the novelty factor of an identified stimulus or as wrongly emphasizing its novelty., Results: At the first observation point (before radiation therapy) all groups underwent a complete standardized neuropsychological examination and performed a battery of cognitive tests. The overall results of the tests assessing attention, memory, thinking processes, and neurodynamic indicators corresponded to standard values. A mild brain compression by the tumor without brain tissue destruction was not accompanied by focal neuropsychological symptoms and deficit manifestations in the cognitive sphere. However, as early as in the first observation point, the number of "pattern separation" errors in the clinical group was significantly higher than that in healthy subjects.The second observation point (immediately after radiotherapy) and the third observation point - 6 months after the treatment - showed that, in general, the patients' cognitive sphere condition was not deteriorating, and in a number of parameters was characterized by positive dynamics, apparently associated with some tumor reduction due to the therapy provided. However, the distribution of errors in the original method significantly changed. When previously memorized stimuli were recognized, the errors neutralizing the novelty factor of the evaluated stimulus increased, while the number of errors with overestimating the stimuli novelty decreased.All tendencies hypothetically (according to the published data) associated with the changes in functional activity of the hippocampus were more pronounced in the subgroup of patients with mechanical impact of the tumor on hippocampus., Conclusion: The continuous flow of impressions any person has at any moment of his activity is most likely marked by the hippocampus in a continuum "old-similar-new". The present study has shown that mechanical impact on the hippocampus combined with radiation exposure changes the range of assessments towards the prevailing labeling "old, previously seen, already known"., Competing Interests: Conflicts of interest. The authors declare no conflicts of interest related to the present study.