Neurocognitive Function Tests Research Articles

Exploring Demographic and Cognitive Predictors of Self-Management in Quasi-Randomized Fall Prevention Intervention for Older Adults With and Without Traumatic Brain Injury.

Changes in health behavior are key to maintaining health, safety, and independence of older adults. The purpose of this study was to explore factors impacting training in self-management and behavior change in older adults with and without traumatic brain injury (TBI), informing efforts to improve safety and independent function. Forty-one older adults, 19 with TBI, completed a self-regulation intervention (mental contrasting with implementation intentions; MCII) to promote fall prevention behavior change. Participant outcomes were related to single and recurring behavior changes; implementation outcomes were measured as modifications to treatment. Although participants with TBI performed more poorly on tests of neurocognitive function, there were no differences in behavior change rates following MCII, suggesting the treatment worked similarly for participants with and without TBI. Across both groups, those with higher executive function scores were more likely to complete recurring behavior changes. Participants with higher stress, higher Fall Risk Scores, or history of TBI were more likely to need modifications to treatment. This quasi-experimental pilot study describes cognitive and psychosocial predictors that may be critical for participation and success in health behavior change and self-management of fall prevention for older adults with and without TBI.

Neurocognitive Function Domains Are Not Affected in Active Professional Male Footballers, but Attention Deficits and Impairments Are Associated with Concussion.

To determine the neurocognitive function of active professional male footballers, determine whether deficits/impairments exist, and investigate the association between previous concussion(s) and neurocognitive function. An observational cross-sectional study conducted via electronic questionnaires. The CNS Vital Signs online testing system was used to evaluate neurocognitive function. Of the 101 participants, 91 completed the neurocognitive function testing. Neurocognitive function domain deficits or impairments were unlikely in 54.5-89.1%, slight in 5.9-21.8%, moderate in 1.0-9.9%, and likely in 4.0-14.9% of participants. A history of zero concussions found a significant association between the neurocognitive index (Odds Ratio [OR] 0.6; 95% CI 0.2-0.4) and complex attention domain (OR 0.3; 95% CI 0.1-0.9), with 40% and 70% less odds, respectively, of deficit/impairment. Among the 54.5% who reported any number of concussions, there were increased odds of neurocognitive domain deficits/impairments for complex attention (CA) [3.4 times more] and simple attention (SA) [3.1 times more]. In the active professional male footballer, most neurocognitive functions do not have significant deficits/impairments. The odds of neurocognitive function deficit/impairment were significantly increased threefold for CA and SA in those who reported a history of any concussion(s).

Challenges with hippocampal MR spectroscopy as a surrogate for pre-radiotherapy assessment of neurocognitive impairment in patients with brain metastasis.

Patients with multiple brain metastases (BM) benefit from hippocampal-avoiding whole brain radiotherapy (HA-WBRT), the challenging and less available form of WBRT. This study explores potential of pre-radiotherapy (pre-RT) hippocampal magnetic resonance spectroscopy (MRS) measuring hippocampal neuronal density as an imaging surrogate and predictive tool for assessing neurocognitive functions (NCF). 43 BM patients underwent pre-RT hippocampal MRS. N-acetyl aspartate (NAA) concentration, a marker for neuronal density (weighted by creatine (Cr) and choline (Cho) concentrations), and neurocognitive function (NCF) tests (HVLT and BVMT) performed by certified psychologists were evaluated. Clinical variables and NAA concentrations were correlated with pre-RT NCFs. HVLT and BVMT subtests showed pre-RT deterioration except for BVMT recognition. Significantly better NCFs were observed in women in HVLT subsets. Significantly higher NAA/Cr + Cho was measured in women (median 0.63 vs. 0.55; P=0.048) in the left hippocampus (no difference in the right hippocampus). In men, a positive correlation (0.51, P=0.018) between total brain volume and HVLT-TR, between left hippocampal NAA/Cr + Cho and HVLT-R (0.45, P=0.063), and between right hippocampal NAA/Cr + Cho and BVMT-recognition (0.49, P=0.054) was observed. In women, a borderline significant negative correlation was observed between left hippocampal NAA/Cr + Cho and BVMT-TR (-0.43, P=0.076) and between right NAA/Cr + Cho and HVLT-DR (-0.42, P=0.051). Borderline statistically significant correlations were observed with speculative interpretation underlying the challenges of hippocampal MRS as a surrogate for neurocognitive impairment. Further studies need to be done to ascertain the opportunities for imaging predictors of benefit from memory sparing radiotherapy.

Effects of Pulsatile and Non-Pulsatile Cardiopulmonary Bypass Techniques in Coronary Artery Bypass Grafting Surgeries on Cerebral Perfusion.

We aimed to evaluate the effects of cardiopulmonary bypass (CPB) machines used in coronary artery bypass grafting surgeries on cerebral perfusion by performing cerebral oximetry monitoring [near-infrared spectroscopy (NIRS)], S100-β protein measurements, and neurocognitive function assessment tests using both pulsatile and non-pulsatile modes. A total of 44 patients, 22 non-pulsatile (Group NP) and 22 pulsatile (Group P), were included in the study. Hemodynamic parameters, arterial blood gas values, NIRS values and blood S100β protein levels were analyzed at five points: pre-induction (T1), initiation of CPB (T2), termination of CPB (T3), end of surgery (T4), and postoperative 24 h (T5). Two different neuropsychological tests were administered to patients in the preoperative and postoperative periods. There were no significant differences between the groups for demographic characteristics such as age, gender, body mass index, aortic cross-clamping, CPB, and operation durations. The mean arterial blood pressure and PaO2 values for the T2 measurements were significantly higher in group NP (P < 0.05). Regional cerebral oxygen saturation (rSO2) (NIRS) values at T3 and T4 were significantly higher in group P (P < 0.05). Serum S100β measurement values at T3 and T5 were significantly higher in group NP than in group P (P < 0.05). Serum S100β protein levels at T3 correlate with rSO2 results. There was no statistically significant difference between the two groups in terms of pH, lactate, glucose, partial pressure of carbon dioxide, and peripheral oxygen saturation values. Despite no difference between the two groups for neurocognitive function tests, we believe that pulsatile perfusion may be more beneficial for cerebral perfusion when S100β protein and NIRS values are considered. Further clinical studies are needed to evaluate the benefits of the pulsatile technique for cerebral perfusion.

Neurophysiological cognitive assessment and its association with neutrophil to lymphocyte ratio

Relevance. Cognition is an important physiological and higher mental functions in human being. There are various studies showing that inflammatory condition could negatively affect fronto temporal cognitive abilities such as memory, attention and executive functions. A non-invasive test P300 a component of Auditory events related potentials and Mini mental state examination (MMSE), a questionnaire based test reflect cognitive function, and haematological parameter neutrophil/lymphocyte ratio (NLR) is a convenient parameter of systemic inflammation. Aim of present study was to assess the cognitive function assessment by P-300, MMSE and academic performance and find an association with neutrophil to lymphocyte ratio in first year medical students. Materials and Methods. This was an observational study conducted on 79 first year medical students of age group 18-25 years in the department of physiology RUHS College of medical sciences Jaipur. For cognitive assessment non-invasive test P300, MMSE and academic performance was recorded. A haematological parameter NLR was calculated by dividing the absolute neutrophil count with the absolute lymphocyte count. To find an association statistical analysis was done by MEDCALC 16.4 version software. Results and Discussion. The association between P-300 amplitude and latency and MMSE with NLR was found non-significant. Marks have a significant positive correlation with NLR (0.015). Conclusion. In the present study neurocognitive function test P-300 and MMSE found non-significant association with inflammatory marker NLR although academic performance (marks) have a significant positive correlation with NLR.

경도인지장애 환자에서 전산화 인지훈련 프로그램의 효과

Objective: As the elderly population increases, the proportion of neurocognitive disorder is increasing. Accordingly, research on cognitive intervention therapy to prevent neurocognitive disorder is also becoming active. In particular, this study attempted to evaluate changes in cognitive function before and after training and verify their effectiveness by implementing a computerized cognitive training program for patients with mild cognitive impairment.&#x0D; Methods: A computerized cognitive training program was conducted for 15 patients with mild cognitive impairment. It was conducted twice a week, 30 minutes, and 16 times for 8 weeks, and neurocognitive function was evaluated before and after training. The neurocognitive function tests are as follows; Seoul Neuropsychological Screening Battery, Korean version of Montreal Cognitive Assessment (K-MoCA), Clinical Dementia Rating (CDR), Korean Instrumental Activity of Daily Living (K-IADL), Korean Neuropsychiatric Inventory (K-NPI), and Memory Age-associated Complaint Questionnaire (MAC-Q).&#x0D; Results: There was a statistically significant improvement in memory domain after the implementation of the computerized cognitive training program, but no significant changes in attention, language ability, visuospatial function, and frontal lobe executive function. Among the memory areas, the Seoul Verbal Learning Test: Delayed Recall, Rey Complex Figure Test: Delayed Recall, and Rey Complex Figure Test: Recognition are showed significant improvement. In addition, there was a significant improvement in CDR (sum of box) and K-MoCA scores. There was no statistically significant difference in K-IADL and K-NPI.&#x0D; Conclusion: Computerized cognitive training programs have been effective in improving memory in patients with mild cognitive impairment. In order to verify the effectiveness of dementia prevention, a long-term study of a larger number is needed. The results of this preliminary study will help develop and apply cognitive training contents in the future.

알코올 사용장애와 알츠하이머 병 환자의 인지기능 평가 차이에 관한 비교 연구

Objectives: There are a few studies on how much and which cognitive function is specifically damaged by chronic alcohol drinking. By comparing neurocognitive function test results between patients with alcohol use disorder and those with Alzheimer’s disease, we aimed to find out which neurocognitive function is damaged by chronic alcohol drinking. In addition, we investigated whether the structural changes in the brain were related to cognitive function decline.&#x0D; Methods: Korean Wechsler Adult Intelligence Scale-IV and Seoul Neuropsychological Screening Battery-II were performed among patients who were diagnosed with Alzheimer’s disease and those who were diagnosed with alcohol use disorder at the department of psychiatry in Pusan National University Yangsan Hospital from November 2008 to May 2022. Among the neurocognitive domains, intelligence quotient, memory quotient, executive intelligence quotient, auditory attention and visual attention were compared. Among those who underwent cognitive function tests, the reading results for brain CT or MRI were compared.&#x0D; Results: There was no significant difference between the two groups in visual attention (p=0.219). Meanwhile, structural changes in the brain were less in the alcohol use disorder group compared to the Alzheimer’s disease group.&#x0D; Conclusion: Chronic drinking, impaired especially, visual attention to the level of Alzheimer’s disease at a relatively early age. Additional research on cognitive function impairment in alcohol use disorders is needed, referring to the results of this study.

Neuroimaging and Neurocognitive Outcomes in Older Patients with Multiple Myeloma Treated with Chemotherapy and Autologous Stem Cell Transplantation.

There is a paucity of research on treatment-related neurotoxicity in older adults with multiple myeloma (MM) treated with high-dose chemotherapy (HDC) and autologous SCT (HDC/ASCT), despite the increasing use of this regimen. We examined resting state functional connectivity (RSFC), gray matter (GM) volume, neurocognitive function (NF), and proinflammatory cytokines (PCy) in older patients with MM pre- and post-HDC/ASCT. Eighteen patients underwent MRI, NF tests, and serum PCy measurements prior to HDC/ASCT, and fifteen patients completed a follow up five-months post-HDC/ASCT. There were significant decreases in RSFC post-HDC/ASCT in (1) the central executive network (CEN) involving the left dorsolateral prefrontal cortex and right posterior parietal cortex (p = 0.022) and (2) the CEN involving the right posterior parietal cortex and the salience network involving the right dorsal anterior cingulate cortex (p = 0.029). There were no significant changes in GM or NF, except for improvements in attention (Digit Span Backward, p = 0.03). There were significant increases in several PCy post-HDC/ASCT (p ≤ 0.05). In conclusion, RSFC decreased in frontal, parietal, and cingulate cortices post-HDC/ASCT, NF was relatively stable, and several PCy increased. These findings are congruent with other studies in cancer patients and provide supporting evidence for the vulnerability of frontoparietal regions to chemotherapy's adverse effects.

Association of chocolate consumption with neurological and cardiovascular outcomes in atrial fibrillation: data from two Swiss atrial fibrillation cohort studies (Swiss-AF and BEAT-AF).

To assess the associations of chocolate consumption with neurocognitive function, brain lesions on magnetic resonance imaging (MRI), and cardiovascular outcome in patients with atrial fibrillation (AF). We analysed data from patients of two prospective multicentre Swiss atrial fibrillation cohort studies (Swiss-AF) and (BEAT-AF). Assessments of MRI findings and neurocognitive function were performed only in the Swiss-AF population (in 1727 of 2415 patients [71.5%] with a complete data set), as patients enrolled in BEAT-AF were not systematically evaluated for these outcomes. Otherwise, the two cohorts had an equivalent set of clinical assessments. Clinical outcome analysis was performed in 3931 patients of both cohorts. Chocolate consumption was assessed by questionnaire. Patients were categorised as no/low chocolate consumption (No/Low-Ch) ≤1 servings/week, moderate chocolate consumption (Mod-Ch) >1-6 servings/week, and high chocolate consumption (High-Ch) >6 servings/week, respectively. Brain lesions were evaluated by MRI. Assessment of cognitive function was performed by neurocognitive functional testing and included global cognition measurement with a cognitive construct score. Cerebral MRI and cognition were evaluated at baseline. Cross-sectional associations between chocolate consumption and MRI findings were analysed by multivariate logistic regression models and associations with neurocognitive function by multivariate linear regression models. Clinical outcome events during follow-up were recorded and assessed by a clinical event committee. The associations between chocolate consumption and clinical outcomes were evaluated by Cox regression models. The median follow-up time was 6 years. Chocolate consumption was not associated with prevalence or volume of vascular brain lesions on MRI, nor major adverse cardiac events (ischaemic stroke, myocardial infarction, cardiovascular death). However, No/Low-Ch was independently associated with a lower cognitive construct score compared to Mod-Ch (No/Low-Ch vs. Mod-Ch: coeff. -0.05, 95% CI -0.10-0), whereas other neurocognitive function tests were not independently associated with chocolate consumption categories. In addition, there was a higher risk of heart failure hospitalisation (No/Low-Ch vs. Mod-Ch: HR 1.24, 95% CI 1.01-1.52) and of all-cause mortality (No/Low-Ch vs. Mod-Ch: HR 1.29, 95% CI 1.06-1.58) in No/Low-Ch compared to Mod-Ch. No significant associations with the evaluated outcomes were observed when High-Ch was compared to Mod-Ch. While chocolate consumption was not associated with MRI findings and major adverse cardiac events in an atrial fibrillation population, No/Low-Ch was associated with a lower cognitive construct score, higher risk of heart failure hospitalisation and increased all-cause mortality compared to Mod-Ch. gov Identifier: NCT02105844.

Hippocampal avoidance in whole brain radiotherapy and prophylactic cranial irradiation: a systematic review and meta-analysis.

We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function. PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing. Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [-0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint. Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up.

Neurocognitive function outcomes in NRG/RTOG 0534, the SPPORT trial.

12022 Background: RTOG 0534 established the benefit of adding of short term androgen deprivation therapy (PBRT+STADT, Arm 2) to prostate bed salvage radiotherapy (PBRT, Arm 1), and demonstrated that elective pelvic lymph node irradiation combined with STADT (PBRT+STADT+PLNRT, Arm 3) results in further reductions in progression. Longitudinal monitoring of neurocognitive function (NCF) was conducted to evaluate the hypothesis that patients treated with STADT will demonstrate greater decline in NCF compared to patients receiving PBRT alone. Methods: Patients were administered the Clinical Trial Battery [Hopkins Verbal Learning Test – Revised (HVLT-R), Trail Making Test (TMT), and the Controlled Oral Word Association (COWA) test] by certified test administrators at baseline, and at 6 weeks (6w), 1 year (1yr), and 5 years after the end of RT (5yr). Raw NCF tests scores were converted to standardized z-scores adjusted for age and education when necessary. Analyses included z-score change and reliable change index (RCI) determined decline compared to baseline, and longitudinal mixed effect regression models using z-scores. To control for multiplicity, p &lt; 0.025 is required for statistical significance. Results: Among the 1716 analyzable patients, 429 consented to NCF monitoring. There were no significant differences in sociodemographic or clinical characteristics between arms. NCF test completion was 82, 76, 63 and 30% at baseline, 6w, 1yr, and 5yr, respectively. RCI-based NCF deterioration was more frequent in Arm 3 compared to Arm 1 at 6 weeks on Delayed Recall (16% vs. 7%, p = 0.023). Patients in Arm 3 evidenced greater z-score decline compared to patients in Arm 1 at 6w on HVLT-R Total Recall [M(SD) Z-score∆ = -0.1(1.0) vs 0.2(0.9), (p = 0.020)] and Delayed Recall [M(SD) Z-score∆ = -0.4(1.5) vs 0.1(1.2), (p = 0.012)]. Mixed effects models identified statistically significant differences in z-scores between Arm 3 and 1 at 6w on Delayed Recall [-0.541 (SE 0.178, p = 0.002)]. A statistically significant difference was observed between Arm 2 and 1 at 6w on TMTB [1.498 (SE 0.626, p = 0.017) favoring Arm 2]. Between arm differences were not seen at any other time point, or on other NCF outcomes. Conclusions: Compared to patients treated with PBRT alone, patients treated with PBRT+STADT+PLNRT exhibited greater worsening in episodic verbal learning and memory processes at 6 weeks after the end of RT, while patients treated with PBRT+STADT exhibited greater improvement in processing speed. The absence of long term or progressive cognitive decline associated with STADT-containing regimens is promising but limited by substantial missing data at year 5. FUNDING This project was supported by grants 10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), CTEP from the National Cancer Institute (NCI). Clinical trial information: NCT00567580 .

Reversible large-scale network disruption correlates with neurocognitive improvement in HIV-associated minor neurocognitive disorder with combined anti-retroviral therapy intensification: a prospective longitudinal resting-state functional magnetic resonance imaging study.

HIV-associated neurocognitive disorder (HAND) affects multiple cognitive domains and currently, the neuropsychological testing is the gold standard to identify these deficits. The aim of this longitudinal 12-month pilot study is to determine the effect of intensified combination antiretroviral therapy (cART) on rs-fMRI in virally suppressed (both in CSF and blood) patients with active HAND (those who have progressive neurocognitive impairment) and correlated with neurocognitive function tests. In this pilot study, we have evaluated sixteen patients with active HAND with viral suppression in both blood and CSF to study the effect of cART on functional connectivity. Participants underwent rs-fMRI at the baseline (time point-1 (TP-1) and 12-month visits (time point-2 (TP-2)). Connectivity in the five major networks was measured at TP-1 and TP-2 using the seed-based approach. All the participants underwent a five-domain neuropsychological battery at TP-1 and TP-2. Neurocognitive scores (NC) as well as blood and CSF markers were correlated with functional connectivity (FC). There was a significant increase in the FC between the two time points within the executive, salience, default mode, dorsal attention, and visual networks at voxel level threshold of p < 0.001 and cluster level threshold of p < 0.05 and corrected for false detection rate (FDR). The neurocognitive scores were positively correlated with all the networks at similar cluster and voxel level thresholds. These results indicate that rs-fMRI can be potentially used as one of the biomarkers for treatment efficacy in HAND.

Phase I dose-escalation study of procaspase-activating compound-1 in combination with temozolomide in patients with recurrent high-grade astrocytomas.

Procaspase-3 (PC-3) is overexpressed in various tumor types, including gliomas. Targeted PC-3 activation combined with chemotherapy is a novel strategy for treating patients with high-grade gliomas, with promising preclinical activity. This study aimed to define safety and tolerability of procaspase-activating compound-1 (PAC-1) in combination with temozolomide (TMZ) for patients with recurrent high-grade astrocytomas. A modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered at increasing dose levels (DL; DL1 = 375 mg) on days 1-21, in combination with TMZ 150 mg/m2/5 days, per 28-day cycle. Dose-limiting toxicity was assessed during the first 2 cycles. Neurocognitive function (NCF) testing was conducted throughout the study. Eighteen patients were enrolled (13 GBM, IDH-wild type; 2 astrocytoma, IDH-mutant, grade 3; 3 astrocytoma, IDH-mutant, grade 4). Dose escalation was discontinued after DL3 (ie, PAC-1, 625 mg) due to lack of additional funding. Grade 3 toxicity was observed in 1 patient at DL1 (elevated liver transaminases) and 1 at DL 2 (headache). Two partial responses were observed at DL1 in patients with GBM, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated. Two patients had stable disease, and 11 experienced progression. NCF testing did not show a clear relationship between PAC-1 dose, treatment duration, and declines in NCF. Combination of PAC-1 and TMZ was well tolerated up to 625 mg orally daily and TMZ orally 150 mg/m2/5 days per 28-day cycle. The maximum tolerated dose was not reached. Further dose escalation of PAC-1 in combination with TMZ is advised before conducting a formal prospective efficacy study in this patient population.

NCOG-48. A PROSPECTIVE LONGITUDINAL NEUROCOGNITIVE OUTCOME STUDY IN PATIENTS TREATED WITH CAR-T-CELL THERAPY AT 6 MONTHS

Abstract INTRODUCTION Chimeric Antigen Receptor T-cell (CAR-T) therapy carries risk of significant neurocognitive function (NCF) toxicities. Longer term NCF outcomes have yet to be reported. The goal of the current study was to assess NCF prospectively in patients undergoing CAR-T. METHODS Adult patients undergoing CAR-T participated in NCF testing with a cognitive clinical trial battery (CTB) at baseline and 6 months after treatment. Group change on each test and on the composite score (CTBC) was examined with paired t-tests and individual change, defined as +/-1 SD on CTBC, was also reported. RESULTS Forty patients (Mage=62.45, 63% male, 97% Non-Hispanic or Latino) completed NCF testing at baseline, and 28 patients completed NCF measures 6 months post-CAR-T (20 complete CTBC, 8 partial CTB, completed virtually). At baseline, 13/40 patients (33%) had significant impairment in NCF (CTBC Z-score &amp;lt; -1.5), and 2/20 (10%) were impaired at follow-up. In the 20 individuals with pre- and 6-month post-CAR-T CTBC scores, there was no significant change (t(19)=-0.926; p=0.366). Examination of each individual test score also showed no changes (immediate memory (t(26)=-0.084; p=0.934), delayed memory (t(26)=-0.207; p=0.837), memory recognition (t (26)=-0.062; p=0.951) executive function (t(18)=-0.447, p=0.660), and verbal fluency (t(27)=-0.035, p=0.972)). Individual analyses of CTBC at follow-up found the number of patients with meaningful decline=1 (5%), improvement=2 (10%), and no change=17 (85%) on CTBC. CONCLUSION Although CAR-T can be associated with acute change in NCF, this prospective longitudinal study showed stable cognitive performance 6 months after treatment. To our knowledge, this is the longest prospective longitudinal study of NCF in CAR-T survivors. This study is limited in that some subjects completed NCF testing virtually at follow-up, limiting the sample size for unconfounded comparison of performance. Future work will examine longer term outcomes and subjective cognitive function in CAR-T survivors.

Hippocampal Dosimetry and Neurocognitive Function in Patients Undergoing Stereotactic Radiosurgery for Brain Metastases

Abstract AIMS To measure neurocognitive function (NCF) and correlate with hippocampus dose in patients undergoing stereotactic radiosurgery (SRS) for 1-3 brain metastases. METHOD We conducted a prospective observational study measuring NCF before and after SRS in patients with 1-3 brain metastases and correlated changes with hippocampal dosimetry Patients underwent NCF testing at baseline, 1 month, 3 months and 6 months post SRS and quality of life was measured at each time point. NCF tests included Hopkin’s Verbal learning test, controlled oral word association test and trail making tests. Hippocampus was outlined in line with RTOG guidance and dose was collected from the treatment planning system. RESULTS 36 patients were recruited. Mean age was 64 years, median WHO performance status 1 (range 0-2). At baseline, 65% of patients displayed NCF impairment in at least 1 NCF domain and 33% didn’t exhibit any neurological symptoms. Asymptomatic patients has underlying diagnosis of non-small cell lung cancer or melanoma. NCF impairment was evident at 1, 3 and 6 months for 50%, 66% and 40% patients respectively. Decline at 1 month was associated with higher median dose to 0.1cc of hippocampus (5 Gy vs 2.35 Gy). Association with hippocampal dose and NCF impairment at 3 and 6 months was not observed. CONCLUSION A significant proportion of patients exhibited impaired NCF at baseline with greatest NCF decline seen at 1 months and subsequent recovery of NCF evident at 6 months. Dose to hippocampus 0.1cc may be associated with acute NCF toxicity. Main limitations of this study was small number of patients.

Long-term neurocognitive function after whole-brain radiotherapy in patients with melanoma brain metastases in the era of immunotherapy

BackgroundWhole-brain radiotherapy (WBRT) used to be standard of care for patients suffering from melanoma brain metastases (MBM) and may still be applicable in selected cases. Deterioration of neurocognitive function (NCF) is commonly seen during and after WBRT. Knowledge on long-term effects in melanoma patients is limited due to short survival rates. With the introduction of immune checkpoint inhibitors, patients may experience ongoing disease control, emphasizing the need for paying more attention to potential long-term adverse effects.MethodsIn this single-center study, we identified in a period of 11 years all long-term survivors of MBM who received WBRT at least 1 year prior to inclusion. NCF was assessed by Neuropsychological Assessment Battery (NAB) screening and detailed neurological exam; confounders were documented.ResultsEight patients (median age 55 years) could be identified with a median follow-up of 5.4 years after WBRT. Six patients reported no subjective neurological impairment. NAB screening revealed an average-range score in 5/8 patients. In 3/8 patients a NAB score below average was obtained, correlating with subjective memory deficits in 2 patients. In these patients, limited performance shown in modalities like memory function, attention, and spatial abilities may be considerably attributed to metastasis localization itself. Six out of 8 patients were able to return to their previous work.ConclusionFive of 8 long-term survivors with MBM after WBRT experienced little to no restriction in everyday activities. In 3 out of 8 patients, cognitive decline was primarily explained by localization of the metastases in functionally relevant areas of the brain. The results of our small patient cohort do not support general avoidance of WBRT for treatment of brain metastases. However, long-term studies including pretreatment NCF tests are needed to fully analyze the long-term neurocognitive effects of WBRT

Neuronal Intranuclear Inclusion Disease with Abnormal Peripheral Nerve Conduction

A 70-year-old female presented with progressive gait disturbance. Neurologic examination revealed sensory impairment, hyporeflexia, and sensory ataxia. Nerve conduction study demonstrated mildly decreased velocity in motor nerves. Brain magnetic resonance imaging showed high signal intensities in the corticomedullary junction on diffusion weighted imaging. Neurocognitive function test implied mild cognitive impairment. Based on eosinophilic intranuclear inclusions in pathology, neuronal intranuclear inclusion disease was confirmed. Neuronal intranuclear inclusion needs to be considered when abnormal nerve conduction studies are consistent with abnormal brain imaging findings.

Silibinin Improves the Clinical Scores of Memory Function in Patients with Mild Cognitive Impairment: A Double-Blind, Placebo-Controlled Pilot Study

The aim of pharmacotherapy for moderate cognitive impairment (MCI) is to reduce the present clinical signs and delay the progression of Alzheimer's disease (AD). There is currently no viable pharmacological therapy for the treatment of AD. Early intake of nutraceuticals, on the other hand, may help to alleviate and delay MCI. The goal of this study was to see how silibinin (SIL) supplementation affected cognitive function in older people with memory problems. A total of 85 subjects with memory impairment were randomly assigned to one of two groups: SIL (n = 42) supplied with 250 mg twice daily, or placebo (n = 43) for 16 weeks. A computerized neurocognitive function test was used to assess cognitive function (CNT). When comparing the SIL group to the placebo group, the "verbal learning test index" items of the CNT were significantly improved in the SIL arm (P &lt; 0.05). Supplementing older people with memory impairment with SIL for 16 weeks appears to have a positive impact on their state of "verbal memory." Further studies are highly recommended.

Clinical relevance of the radiation dose bath in lower grade glioma, a cross-sectional pilot study on neurocognitive and radiological outcome

AimTo investigate the clinical relevance of the radiotherapy (RT) dose bath in patients treated for lower grade glioma (LGG). MethodsPatients (n = 17) treated with RT for LGG were assessed with neurocognitive function (NCF) tests and structural Magnetic Resonance Imaging (MRI) and categorized in subgroups based on tumour lateralisation. RT dose, volumetric results and cerebral microbleed (CMB) number were extracted for contralateral cerebrum, contralateral hippocampus, and cerebellum. The RT clinical target volume (CTV) was included in the analysis as a surrogate for focal tumour and other treatment effects. The relationships between RT dose, CTV, NCF and radiological outcome were analysed per subgroup. ResultsThe subgroup with left-sided tumours (n = 10) performed significantly lower on verbal tests. The RT dose to the right cerebrum, as well as CTV, were related to poorer performance on tests for processing speed, attention, and visuospatial abilities, and more CMB.In the subgroup with right-sided tumours (n = 7), RT dose in the left cerebrum was related to lower verbal memory performance, (immediate and delayed recall, r = −0.821, p = 0.023 and r = −0.937, p = 0.002, respectively), and RT dose to the left hippocampus was related to hippocampal volume (r = −0.857, p = 0.014), without correlation between CTV and NCF. ConclusionBy using a novel approach, we were able to investigate the clinical relevance of the RT dose bath in patients with LGG more specifically. We used combined MRI-derived and NCF outcome measures to assess radiation-induced brain damage, and observed potential RT effects on the left-sided brain resulting in lower verbal memory performance and hippocampus volume.

Speed of Information Processing and Working Memory in Children with Cochlear Implants

Background: Cochlear implants (CIs) restore partial hearing to deaf children, promoting the development of spoken language skills. However, because of reduced auditory and language experience, children who receive CIs are at risk for delays not only in language skills but also in language-related neurocognitive skills such as verbal working memory (VWM - the ability to retain language information in immediate memory concurrently with other cognitive processing). Although VWM delays in children with CIs are well-documented, the foundational processes underlying these delays are less clear. This study investigated the hypotheses that slower speed of information processing during VWM tasks contributes to VWM delays in CI users and that this slower information processing speed is associated with spoken language outcomes. &#x0D; &#x0D; Methods: 25 early-implanted, prelingually-deaf children with CIs and 25 normal-hearing (NH) peers completed tests of VWM, neurocognitive, and speech-language functioning. Speed of information processing during the VWM test was assessed by measuring response latency and average pause duration. &#x0D; &#x0D; Results: Children with CIs showed poorer VWM scores than NH peers, but the groups did not differ on response latencies or pause durations. Response latencies were significantly correlated with VWM capacity, speech, and language outcomes in both groups. &#x0D; &#x0D; Conclusion: Speed of information processing in VWM was similar for children with CIs and NH. In both groups, shorter response latencies (faster speed of execution of the cognitive operations of working memory) were associated with better neurocognitive and spoken language outcomes. In the CI sample, pause durations were inconsistently associated with VWM and language outcomes. &#x0D; &#x0D; Clinical Policy Impact and Implications: Speed of information processing for VWM is associated with core neurocognitive and spoken language outcomes for children with CIs and should be a routine target of assessment and intervention post-implantation.