Safety and Feasibility of Hippocampal Sparing Cranial Radiation in Pediatric and Adolescent Acute Lymphoblastic Leukemia Patients: A Prospective Study.

Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT) has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who were in remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

Association of Physical Frailty and Cognitive Function in a Population-Based Cross-Sectional Study of American Older Adults.

INTRODUCTION: Cognitive impairment and frailty are prevalent in older persons. Physical frailty is associated with cognitive decline; however, the role of effect modifiers such as age, sex, race/ethnicity, and cognitive reserve is not well understood. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey (2011-2014) were obtained for participants aged ≥60 years. Complete availability of cognitive scores was an inclusion criterion. Physical frailty was defined by the presence of exhaustion, weakness, low body mass, and/or low physical activity, and categorized into three groups: robust (0 present), pre-frail (1-2 present), or frail (3-4 present). Four cognitive test scores were converted to z-scores, and global cognition (composite z-score) was calculated by averaging the four-individual z-scores. Multivariable linear regression models were fit to estimate the associations between frailty and cognitive function. Frailty was also evaluated as a risk factor for self-reported subjective memory complaint (SMC) using logistic regression. All models were adjusted for age, sex, race/ethnicity, education, alcohol use, income, marital status, diabetes, hypertension, and history of stroke. Effect measure modification analyses were conducted by age, sex, race/ethnicity, education, and occupational cognitive demand. RESULTS: The study population comprised 2,863 participants aged ≥60 years. 50.6% of the participants were categorized into robust, 43.2% pre-frail, and 6.2% frail. After adjusting for covariates, compared to robust participants, frail and prefrail participants had lower adjusted mean global cognitive z-scores, ß^ = -0.61, 95% CI: -0.83, -0.38 and ß^ = -0.21, 95% CI: -0.30, -0.12, respectively. Both prefrail and frail participants had higher odds of SMC compared to the robust participants. We did not see strong evidence that the association between frailty and cognition was modified by the factors we studied. DISCUSSION/CONCLUSION: Both pre-frailty and frailty were associated with lower cognitive performance and were more likely to report subjective memory complaints relative to persons without frailty. These findings provide additional evidence that physical frailty may serve as a prognostic factor for cognitive deterioration or dementia, and prevention of frailty may be an important public health strategy.

Evaluation of the Relationships between Irisin Levels and Cognitive Functions in Individuals with Schizophrenia.

Objective: : Irisin is a myokine that is involved in neurogenesis, neuronal proliferation, and neuronal differentiation. Many research examine the relationship between irisin and schizophrenia. In this study, we aimed to evaluate the relationship between irisin levels and cognitive functions in individuals with schizophrenia. Methods: : Ninety-six individuals who were diagnosed with schizophrenia were included. The Brief Psychiatric Rating Scale (BPRS) was used to assess disease severity. To evaluate the cognitive functions of the patients, the trail-making test was evaluated with the A and B forms and the verbal memory processes scale. After a 12-hour night fast, samples of fasting blood were obtained from the participants. Results: : There was no significant correlation between irisin, duration of disease, and BPRS total score. In the analysis performed, a positive correlation was found between the plasma irisin level and the error score of the trail-making test form B. Other than that, no correlation was found between irisin level and cognitive performance in schizophrenia patients. In addition, in subgroup analysis between genders, it was determined that the duration of the trail-making test B was longer in female schizophrenia patients. Conclusion: : In this study, there was a positive correlation between the trail-making test B-form error scores and the irisin levels. This relationship between impaired executive functions and irisin levels may suggest that the irisin level is increased as compensation for the impairment in executive functions. More research is needed to understand the role of irisin in cognitive impairment and schizophrenia.

Landmark Model-based Individual Dynamic Prediction of Conversion from Mild Cognitive Impairment to Alzheimer's Disease using Cognitive Screening.

BACKGROUND: Identifying individuals with mild cognitive impairment (MCI) who are at increased risk of Alzheimer's Disease (AD) in cognitive screening is important for early diagnosis and prevention of AD. OBJECTIVE: This study aimed at proposing a screening strategy based on landmark models to provide dynamic predictive probabilities of MCI-to-AD conversion according to longitudinal neurocognitive tests. METHODS: Participants were 312 individuals who had MCI at baseline. The longitudinal neurocognitive tests were the Mini-Mental State Examination, Alzheimer Disease Assessment Scale-Cognitive 13 items, Rey Auditory Verbal Learning Test immediate, learning, and forgetting, and Functional Assessment Questionnaire. We constructed three types of landmark models and selected the optimal landmark model to dynamically predict 2-year probabilities of conversion. The dataset was randomly divided into training set and validation set at a ratio of 7:3. RESULTS: The FAQ, RAVLT-immediate, and RAVLT-forgetting were significant longitudinal neurocognitive tests for MCI-to-AD conversion in all three landmark models. We considered Model 3 as the final landmark model (C-index = 0.894, Brier score = 0.040) and selected Model 3c (FAQ and RAVLT-forgetting as neurocognitive tests) as the optimal landmark model (C-index = 0.898, Brier score = 0.027). CONCLUSION: Our study shows that the optimal landmark model with a combination FAQ and RAVLTforgetting is feasible to identify the risk of MCI-to-AD conversion, which can be implemented in cognitive screening.

Performance on the African neuropsychology battery using the learning ratio in a sample of healthy Congolese.

OBJECTIVE: Using the African Neuropsychology Battery (ANB), we seek to develop normative data by examining the demographic effects for two learning process scores: initial learning (Trial One) and learning ratio (LR, the percentage of items learned relative of to-be-learned material following Trial 1). METHODS: Healthy participants from the Democratic Republic of Congo completed the four memory tests of the ANB: the African Story Memory Test (ASMT), African List Memory Test (ALMT), African Visuospatial Memory Test (AVMT), and African Contextual Visuospatial Memory Test (ACVMT). We developed indices of learning for each subtest, as well as aggregate learning indices for Trial 1 and LR, and composite indices examining verbal, visual, contextual, and noncontextual learning, and grand indices comprising all four subtests. RESULTS: Trial 1 and LR scores each demonstrated acceptable intercorrelations across memory tests. We present normative data for Trial 1 and LR by age and education. CONCLUSION: These data provide normative standards for evaluating learning in Sub-Saharan Africa.

Prediction of postpartum depression with an online neurocognitive risk screening tool for pregnant women.

Postpartum depression (PPD) is a severe mental illness affecting 10-15% of mothers. Emerging evidence indicates that negative neurocognitive bias in response to infant distress during pregnancy marks an increased risk of PPD. This proof-of-concept study aimed to investigate the association between negatively biased neurocognitive processing of infant distress during pregnancy and subsequent PPD and to explore the feasibility of an online risk screening tool. In the second or third trimester of pregnancy, 87 participants underwent two online tests of reactivity to and evaluation of infant distress and completed questionnaires regarding psychosocial risk factors. After birth, participants rated their depressive symptoms online and underwent a diagnostic telephone interview concerning PPD. Irrespective of depressive symptoms during pregnancy, negative reactivity to and evaluation of infant distress predicted PPD (reactivity: Exp(B)=1.33, p = 0.04) and depressive symptoms after birth (reactivity: B = 0.04, p = 0.048; evaluation: B = 0.10, p = 0.04). The negative reactivity toward infant distress showed high sensitivity and moderate specificity (89% and 77%, respectively), while the evaluation of infant distressed cries showed lower sensitivity and specificity (67% and 66%, respectively). The relatively small sample size prevented the inclusion of additional risk variables in the regression models. The replication of an association between negative neurocognitive bias during pregnancy with PPD risk is noteworthy and has clinical implications in terms of early prevention. However, the low response rate indicates that this tool is not feasible in its current form. Future larger-scale studies are needed to further investigate candidate risk factors in a brief online screening tool.

Surface electroencephalographic neurofeedback improves sustained attention in ADHD: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of surface electroencephalographic neurofeedback (EEG-NF) for improving attentional performance assessed by laboratory measures in patients with attention-deficit/hyperactivity disorder (ADHD) remains unclear. METHODS: Following the PRISMA guidelines, the PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials on the efficacy of surface EEG-NF against ADHD focusing on attentional performance evaluated by laboratory measures from inception to January 2022. RESULTS: Fourteen eligible studies were analyzed. Of the 718 participants involved, 429 diagnosed with ADHD received EEG-NF treatment. Significant improvement in attentional performance in ADHD subjects receiving EEG-NF was noted compared to their comparators (p < 0.01). Besides, there was a significant EEG-NF-associated beneficial effect on sustained attention (Hedges' g = 0.32, p < 0.01), whereas the impact on selective attention (p = 0.57) and working memory (p = 0.59) was limited. Moreover, protocol including beta wave enhancement was superior to that only focusing on reducing theta/beta ratio or modulation of slow cortical potential. Subgroup analyses showed that three sessions per week of EEG-NF produced the best effect, while the efficacy of surface EEG-NF was much poorer (Hedges' g = 0.05) when only studies that blinded their participants from knowledge of treatment allocation were included. No significant difference was noted in the improvement of attentional performance 6-12 months after EEG-NF intervention (n = 3, p = 0.42). CONCLUSIONS: Our results demonstrated the satisfactory effectiveness of surface EEG-NF for improving sustained attention, especially when beta wave enhancement was included, despite its failure to sustain a long-term effect. Further large-scale trials are warranted to support our findings.

Differential associations between simple physical performance tests with global and specific cognitive functions in cognitively normal and mild cognitive impairment: a cross-sectional cohort study of Asian community-dwelling older adults.

BACKGROUND: Physical performance declines and executive dysfunctions are predictors of dementia. However, their associations are not well understood in Asian older adults without dementia (cognitively normal [CN] and mild cognitive impairment [MCI]), especially in a single study. OBJECTIVE: Examine the associations between physical performance measures with executive function (EF)-based and non-EF-based neurocognitive tests and whether preclinical dementia cognitive status i.e., CN and MCI, moderated these associations. METHODS: We examined cross-sectional cohort of 716 community-dwelling older adults without dementia (CN = 562 and MCI = 154) using multivariable linear regression models. We associated three simple physical performance measures, namely timed-up-and-go (TUG), fast gait speed (FGS), and 30-s chair stand test (30 s-CST), with a comprehensive neurocognitive test battery measuring EF and non-EF cognitive functions. Moderating effects of cognitive status on the associations were examined. In all models, we controlled for pertinent covariates, including age, education, medical and psychiatric status. RESULTS: Upon controlling for covariates, TUG was most strongly and positively associated with multiple EF-based neurocognitive tests, followed by FGS, with 30 s-CST having the weakest associations. For all physical performance measures, no significant associations with non-EF-based neurocognitive tests were detected. Cognitive status significantly moderated the associations between all physical measures and several neurocognitive tests, with stronger associations in the MCI than CN. CONCLUSION: Compared to FGS and 30 s-CST, TUG had the most robust associations with multiple EF-based cognitive functions. Given their differential associations with global and detailed neurocognitive tests and significant moderating effects of cognitive status, findings highlight a need to carefully consider the choices of simple physical performance tests when using these tests with a heterogenous group of community-dwelling older adults without dementia.

Psychometric Properties of Computerized Cognitive Tools and Standard Neuropsychological Tests Used to Assess Sport Concussion: A Systematic Review.

Athletic programs are more frequently turning to computerized cognitive tools in order to increase efficiencies in concussion assessment. However, assessment using a traditional neuropsychological test battery may provide a more comprehensive and individualized evaluation. Our goal was to inform sport clinicians of the best practices for concussion assessment through a systematic literature review describing the psychometric properties of standard neuropsychological tests and computerized tools. We conducted our search in relevant databases including Ovid Medline, Web of Science, PsycINFO, and Scopus. Journal articles were included if they evaluated psychometric properties (e.g., reliability, sensitivity) of a cognitive assessment within pure athlete samples (up to 30 days post-injury). Searches yielded 4,758 unique results. Ultimately, 103 articles met inclusion criteria, all of which focused on adolescent or young adult participants. Test-retest reliability estimates ranged from .14 to .93 for computerized tools and .02 to .95 for standard neuropsychological tests, with strongest correlations on processing speed tasks for both modalities, although processing speed tasks were most susceptible to practice effects. Reliability was improved with a 2-factor model (processing speed and memory) and by aggregating multiple baseline exams, yet remained below acceptable limits for some studies. Sensitivity to decreased cognitive performance within 72 h of injury ranged from 45%-93% for computerized tools and 18%-80% for standard neuropsychological test batteries. The method for classifying cognitive decline (normative comparison, reliable change indices, regression-based methods) affected sensitivity estimates. Combining computerized tools and standard neuropsychological tests with the strongest psychometric performance provides the greatest value in clinical assessment. To this end, future studies should evaluate the efficacy of hybrid test batteries comprised of top-performing measures from both modalities.

A Mini-Mental State Examination Formula May Help to Distinguish Alzheimer's Disease from Dementia with Lewy Bodies.

BACKGROUND: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) differ in their memory, attention, and visuoconstructional characteristics. The subscales of the well-known Mini-Mental State Examination (MMSE) provide an opportunity to assess these characteristics. Previous research has shown that analysis of the MMSE subscale performance of AD and DLB patients helps to differentiate them. OBJECTIVE: Study the MMSE scores of AD and DLB patients to see if the ability of previously reported analyses to differentiate them could be improved. Include other dementia patients for perspective. METHODS: We studied the MMSEs of all patients seen in our clinics during an 18-month period. Different equations were studied, derived from the subscales of Memory (M, 3 points maximum), Attention (A, 5 points maximum), and Pentagon-copying (P, 1 point maximum). RESULTS: We obtained 400 MMSEs, 136 from AD patients and 24 from DLB patients, scoring range 1-30. The equation P minus M provided the best discrimination between AD and DLB. Using a P-M score = 1 to identify AD, the positive predictive value was 0.97, negative predictive value 0.22, specificity 0.92, and sensitivity 0.43. As a secondary finding, the P-M = 1 equation was also helpful to differentiate AD from Parkinson's disease dementia. CONCLUSION: Considering AD versus DLB in our clinic population, a demented patient who was unable to recall the three memory words on the MMSE but able to copy the intersecting pentagons had a 97% likelihood of having AD. Additional work is needed to improve the sensitivity of the P-M = 1 equation.

Clinical Progression of Baseline Risk States for Mild Cognitive Impairment.

BACKGROUND: This memory-clinic study joins efforts to study earliest clinical signs and symptoms of Alzheimer's disease and related dementias: subjective reports and objective neuropsychological test performance. OBJECTIVE: The memory-clinic denoted two clinical "grey zones": 1) subjective cognitive decline (SCD; n = 107) with normal objective test scores, and 2) isolated low test scores (ILTS; n = 74) without subjective complaints to observe risk for future decline. METHODS: Initial and annual follow-up clinical research evaluations and consensus diagnosis were used to evaluate baseline characteristics and clinical progression over 2.7 years, compared to normal controls (NC; n = 117). RESULTS: The ILTS group was on average older than the NC and SCD groups. They had a higher proportion of people identifying as belonging to a minoritized racial group. The SCD group had significantly more years of education than the ILTS group. Both ILTS and SCD groups had increased risk of progression to mild cognitive impairment. Older age, minoritized racial identity, and baseline cognitive classification were risk factors for progression. CONCLUSION: The two baseline risk groups look different from each other, especially with respect to demographic correlates, but both groups predict faster progression than controls, over and above demographic differences. Varied presentations of early risk are important to recognize and may advance cognitive health equity in aging.

Usability of the Virtual Supermarket Test for Older Adults with and without Cognitive Impairment.

This study conducted a preliminary usability assessment of the Virtual Supermarket Test (VST), a serious game-based self-administered cognitive screening test for mild cognitive impairment (MCI). Twenty-four healthy older adults with subjective cognitive decline and 33 patients with MCI self-administered the VST and then completed the System Usability Scale (SUS). The average SUS score was 83.11 (SD = 14.6). The SUS score was unaffected by age, education, touch device familiarity, and diagnosis of MCI. SUS score correlated with VST performance (r = -0.496, p = 0.000). Results of this study indicate good usability of the VST.

The Sleep Revolution project: the concept and objectives.

Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.

Anticholinergic Drug Burden and Neurocognitive Performance in the Study of Latinos-Investigation of Neurocognitive Aging.

BACKGROUND: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos. OBJECTIVE: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos. METHODS: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change. RESULTS: Anticholinergic use was associated with lower cognitive global cognition (ß= -0.21; 95% CI [-0.36; -0.05]), learning (ß= -0.27; 95% CI [-0.47; -0.07]), memory (ß= -0.22; 95% CI [-0.41; -0.03]), and executive functioning (ß= -0.22; 95% CI [-0.40; -0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (ß: -0.28 [95% CI: -0.55, -0.01]; ß: -0.28 [95% CI: -0.55, -0.01]; ß: -0.25, [95% CI -0.47, -0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F3 = 3.59, F3 = 2.84, F3 = 3.88, respectively). CONCLUSION: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

Neurocognitive Functions Related to Parietal Lobe in Patients with Schizophrenia and Methamphetamine Induced Psychotic Disorder and Healthy Individuals: A Comparative Study.

Background: There are some inconsistent findings about neurocognitive functions in schizophrenia and methamphetamine induced psychosis (MIP). This study aimed to compare these two disorders in terms of neurocognitive functions related to parietal lobe. Methods: This was a cross-sectional study in which 30 patients with schizophrenia, 30 patients with MIP, and 32 healthy individuals were compared. The two groups of patients were selected through convenience sampling from among patients hospitalized in Shahid Beheshti hospital in Kerman, Iran and healthy individuals were selected via convenience sampling from among the employees of Kerman University of Medical Sciences. The three groups were administered clock-drawing test (CDT), Rey-Osterrieth complex figure (ROCF) copying test, and interlocking finger test (IFT) and their demographic and clinical data were collected. The one-way analysis of variance (ANOVA) was used to investigate the differences between the groups. Multivariate analysis of covariance was also used to examine the effects of confounding factors. Besides, follow-up pairwise comparisons were performed after adjustment for multiple testing. Findings: The group with schizophrenia had significantly more impairment than the group with MIP with reference to the results of IFT and the ROCF test. However, the scores of patients with MIP on these two tests were not different from those of the normal controls. With regard to the CDT, the only significant difference was observed between the group with schizophrenia and controls. Conclusion: On the condition that the results are replicated in other studies, some parietal lobe neurocognitive tests might be used when it is difficult to differentially diagnose schizophrenia and MIP.

Tau deposition and structural connectivity demonstrate differential association patterns with neurocognitive tests.

Tau neurofibrillary tangles have a central role in the pathogenesis of Alzheimer's Disease (AD). Mounting evidence indicates that the propagation of tau is assisted by brain connectivity with weakened white-matter integrity along the propagation pathways. Recent advances in tau positron emission tomography tracers and diffusion magnetic resonance imaging allow the visualization of tau pathology and white-matter connectivity of the brain in vivo. The current study aims to investigate how tau deposition and structural connectivity are associated with memory function in prodromal AD. In this study, tau accumulation and structural connectivity data from 83 individuals (57 cognitively normal participants and 26 participants with mild cognitive impairment) were associated with neurocognitive test scores. Statistical analyses were performed in 70 cortical/subcortical brain regions to determine: 1. the level of association between tau and network metrics extracted from structural connectivity and 2. the association patterns of brain memory function with tau accumulation and network metrics. The results showed that tau accumulation and network metrics were correlated in early tau deposition regions. Furthermore, tau accumulation was associated with worse performance in almost all neurocognitive tests performance evaluated in the study. In comparison, decreased network connectivity was associated with declines in the delayed memory recall in Craft Stories and Benson Figure Copy. Interaction analysis indicates that tau deposition and dysconnectivity have a synergistic effect on the delayed Benson Figure Recall. Overall, our findings indicate that both tau deposition and structural dysconnectivity are associated with neurocognitive dysfunction. They also suggest that tau-PET may have better sensitivity to neurocognitive performance than diffusion MRI-derived measures of white-matter connectivity.

Whole Brain Irradiation or Stereotactic RadioSurgery for five or more brain metastases (WHOBI-STER): A prospective comparative study of neurocognitive outcomes, level of autonomy in daily activities and quality of life.

AIMS: To evaluate neurocognitive performance, daily activity and quality of life (QoL), other than usual oncologic outcomes, among patients with brain metastasis ≥5 (MBM) from solid tumors treated with Stereotactic Brain Irradiation (SBI) or Whole Brain Irradiation (WBI). METHODS: This multicentric randomized controlled trial will involve the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy > 3 months, known primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) score ≥ 20/30, Barthel Activities of Daily Living score ≥ 90/100, to be submitted to SBI by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBI (control arm). The primary endpoints are neurocognitive performance, QoL and autonomy in daily-life activities variations, the first one assessed by MoCa Score and Hopkins Verbal Learning Test-Revised, the second one through the EORTC QLQ-C15-PAL and QLQ-BN-20 questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatment rate, acute and late toxicities, changing of KPS. It will be considered significant a statistical difference of at least 30% between the two arms (statistical power of 80% with a significance level of 95%). DISCUSSION: Several studies debate what is the decisive factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiation effect on clinically healthy brain tissue or intracranial tumor burden? The answer to this question may come from the recent technological advancement that allows, in a context of a significant time saving, improved patient comfort and minimizing radiation dose to off-target brain, a selective treatment of MBM simultaneously, otherwise attackable only by WBI. The achievement of a local control rate comparable to that obtained with WBI remains the fundamental prerequisite. TRIAL REGISTRATION: NCT number: NCT04891471.

Neuropsychological and Neurophysiological Assessment in Different Phases of Bipolar Disorder.

Background: Recent studies have shown that cognitive deficits are significant and pervasive even among remitted bipolar disorder patients. The aim of the current controlled study was to investigate the relationships between cognitive performances, symptom severity, and event-related potentials with regard to different episodes in bipolar patients. Methods: This study was conducted on a total of 60 patients diagnosed with bipolar disorder (20 depressive, 20 manic, and 20 in remission). The Frontal Assessment Battery and Stroop test were used for neuropsychological assessment. Event-related potentials were measured using frontal, central, and parietal EEG recordings, while Nihon-Kohden EMG-EP system was used. Results: Delayed P300 latencies were observed in all phases of bipolar disorder when compared to the controls. There was a positive relationship between frontal, central P300 latencies, and Young Mania Rating Scale scores. A strong positive relationship was also observed between Young Mania Rating Scale scores and Stroop interference scores. A negative relationship was observed between Frontal Assessment Battery scores and frontal, central, and parietal N100 latencies and amplitudes in depressed patients. Consistent with these findings, there was a relationship between Hamilton Depression Rating Scale scores and N100 latencies. There was also a positive relationship between Stroop interference scores and central N200 latency, as well as frontal N200 and parietal N200 amplitudes, while a negative relationship was observed between Stroop total time scores and central N200 latency as well as parietal N200 amplitude in depressed patients. Conclusions: Study findings imply that depression episodes could be associated with decision-making autonomy and memory issues, while there is also a relationship between episodes of mania, impaired inhibitory control, and issues with selective attention. Moreover, these cognitive impairments might be included in the initial phases of processing observed in N100 responses in depression, while processing impairment could be pervasive in mania that results in P300 delays.

Omega-3 fatty acids are associated with blood-brain barrier integrity in a healthy aging population.

In aging populations, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with better cognitive function, slower rates of cognitive decline, and lower risk of developing dementia. Animal studies have shown that diets rich in omega-3 PUFAs reduce blood-brain barrier (BBB) disruption associated with aging, but this has yet to be observed in humans. Forty-five healthy subjects (mean age, 76 years) were recruited and underwent cognitive assessment (verbal learning and memory, language, processing speed, executive function, and motor control) and measurement of PUFAs. Forty of the same subjects also underwent magnetic resonance imaging (MRI) to measure BBB integrity (Ktrans using dynamic contrast-enhanced MRI). The long chain omega-3 score (DHA+EPA) was negatively correlated with Ktrans values in the internal capsule, indicating higher omega-3 levels were associated with greater BBB integrity in this region (r = -0.525, p = .004). Trends were observed for a positive correlation between the long chain omega-3 score and both memory and language scores, but not with executive function, speed, or motor control. The omega-6 score was not significantly correlated with any cognitive scores or Ktrans values. The significant correlations between long chain omega-3 levels and BBB integrity provide a possible mechanism by which omega-3 PUFAs are associated with brain health.