Changes In Neurocognitive Function Research Articles

A - 125 Exploring the Relationship between the NIH Toolbox-Cognitive Battery & the Alzheimer’s Disease Cooperative Study-Preclinical Cognitive Composite

Abstract Objective The computerized NIH Toolbox–Cognitive Battery (NIHTB-CB) is efficient but has not been widely used clinically. The Alzheimer’s Disease Cooperative Study-Preclinical Alzheimer Cognitive Composite (ADS-PACC) has good sensitivity and correlates with amyloid pathology. This study examined the relationship between the NIHTB-CB and ADS-PACC in an aging adult population. Method Baseline data from the Risk Reduction for Alzheimer’s Disease (rrAD) study were analyzed. Cognitively intact individuals (n = 511, M MMSE = 29) with hypertension and subjective cognitive complaints and/or a first degree relative with dementia were included (M age = 68.73, 63% female; 84% White, M education = 16.24). Multiple regression examined the relationship between the NIHTB-CB subtests and ADS-PACC composite score. Results NIHTB-CB subtests demonstrated small to moderate positive correlations with the ADS-PACC total score (r = 0.19–0.43, p < 0.001). ADS-PACC performance explained 23.5% of the variance for NIHTB-CB Flanker Inhibitory Control/Attention [F, (4, 510) = 40.19, p < 0.001], 18.1% for Pattern Comparison Processing Speed, 13.9% for List Sorting Working Memory [F, (4, 508) = 21.53, p < 0.001], and 13.2% for Dimensional Change Card Sort [F, (4, 510) = 20.43, p < 0.001]. Conclusions The NIHTB-CB and ADS-PACC showed modest correlations, but PACC scores explained a sizeable amount of variance of NIHTB-CB performance. Previous research supports convergent validity of the NIHTB-CB with other commonly used neuropsychological measures; however, results of this study indicate these batteries may assess different aspects of cognitive functioning. Future research may explore the relationship between the two batteries and their components in the assessment of longitudinal changes in neurocognitive function in individuals with cognitive decline/dementia.

Longitudinal Study of Cognitive Function in People with HIV and Toxoplasmic Encephalitis or Latent toxoplasma Infection.

Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related CNS co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on NC functioning in PWH with TE compared to LTI or no toxoplasmal infection. PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-Toxoplamic IgG assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI- (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit. The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/mL) and had lower absolute CD4 counts. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants. PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

Change in Neurocognitive Function in Patients Who Receive CAR-T Cell Therapies: A Steep Hill to Climb.

Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients.

“Why am I still suffering?”: Experience of long-term fatigue and neurocognitive changes in oropharyngeal cancer survivors following (chemo)radiotherapy

BackgroundLate effects of cancer treatment, such as neurocognitive deficits and fatigue, can be debilitating. Other than head and neck–specific functional deficits such as impairments in swallowing and speech, little is known about survivorship after oropharyngeal cancer. This study examines the lived experience of fatigue and neurocognitive deficits in survivors of oropharyngeal squamous cell cancer and impact on their daily lives. MethodsThis work is part of the multicentre mixed method ROC-oN study (Radiotherapy for Oropharyngeal Cancer and impact on Neurocognition), evaluating fatigue and neurocognitive function in patients following radiotherapy +/- chemotherapy for oropharyngeal cancer and impact on quality of life. Semi-structured interviews were conducted in adults treated with radiotherapy (+/-chemotherapy) for oropharyngeal squamous cell carcinoma >/=24 months from completing treatment. Reflexive thematic analysis performed. Results21 interviews (11 men and 10 women; median age 58 years and median time post-treatment 5 years) were conducted and analysed, yielding six themes: (1) unexpected burden of fatigue, (2) noticing changes in neurocognitive function, (3) the new normal, (4) navigating changes, (5)insufficient awareness and (6)required support. Participants described fatigue that persisted beyond the acute post-treatment period and changes in neurocognitive abilities across several domains. Paid and unpaid work, emotions and mood were impacted. Participants described navigating the new normal by adopting self-management strategies and accepting external support. They reported lack of recognition of these late effects, being poorly informed and being unprepared. Follow-up services were thought to be inadequate. ConclusionsFatigue and neurocognitive impairment were frequently experienced by survivors of oropharyngeal cancer, at least two years after treatment. Patients felt ill-prepared for these late sequelae, highlighting opportunities for improvement of patient information and support services.

Evaluating the sensitivity of EQ-5D-5L in patients with brain metastases: a secondary analysis of NRG CC001.

EuroQoL EQ-5D is a commonly used measure of health-related quality of life (HRQOL) in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes. A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups. EQ-5D-5L index and VAS score changes between patients who had cognitive failure and those that had preserved cognition showed no significant differences at any time point. In contrast, VAS changes at 4 (1.61 vs -5.13, P = .05) and 6 months (8.17 vs -0.14, P = .04) were significantly improved in the patients who survived without intracranial progression.MDASI-BT cognitive factor scores were significantly improved in the cohort of patients with preserved neurocognitive function at 2 (1.68 vs 2.08, P = .05) and 4 months (1.35 vs 1.83, P = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status. EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a QoL metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction. NCT# 02360215.

Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases

The potential benefit of combining intracranial effective systemic therapy with radiotherapy for patients with breast cancer with brain metastases remains unclear. To assess the activity and safety of combining radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive breast cancer and brain metastases. This was a single-arm, single-center, phase 2 nonrandomized clinical trial with a safety run-in phase. Between January 2020 and August 2022, patients with ERBB2-positive breast cancer and brain metastases were enrolled. The data cutoff date was February 1, 2023. Patients received either fractionated stereotactic radiotherapy or whole-brain radiotherapy. Treatment with pyrotinib (400 mg, once daily) and capecitabine (1000 mg/m2, twice daily, on days 1-14 of each 21-day cycle) was initiated from the first day of radiotherapy to the seventh day after the completion of radiotherapy and continued until disease progression or unacceptable toxic effects. The primary end point was 1-year central nervous system (CNS) progression-free survival (PFS) rate. Secondary end points included CNS objective response rate (ORR), PFS, overall survival (OS), safety, and changes in neurocognitive function. A total of 40 female patients (median age, 50.5 years [IQR, 46-59 years]) were enrolled and received treatment, including 3 patients in safety run-in phase. With a median follow-up of 17.3 months (IQR, 10.3-26.9), the 1-year CNS PFS rate was 74.9% (95% CI, 61.9%-90.7%), and the median CNS PFS was 18.0 months (95% CI, 15.5 to not reached). The 1-year PFS rate was 66.9% (95% CI, 53.1%-84.2%), and the median PFS was 17.6 months (95% CI, 12.8-34.1). The CNS objective response rate was 85% (34 of 40). Median overall survival was not reached. The most common grade 3 or 4 treatment-related adverse event was diarrhea (7.5%). Asymptomatic radiation necrosis was identified in 4 of 67 lesions (6.0%) treated with fractionated stereotactic radiotherapy. Most patients maintained neurocognitive function, as evaluated by the Mini-Mental State Examination at different points. The results of this trial suggest that radiotherapy combined with pyrotinib and capecitabine is associated with long intracranial survival benefit in patients with ERBB2-positive advanced breast cancer and brain metastases with an acceptable safety profile. This combination deserves further validation. ClinicalTrials.gov Identifier: NCT04582968.

In-depth Analysis of Lorlatinib-related neurocognitive Adverse Events in Patients With Non–small-cell Lung Cancer

IntroductionLorlatinib is a potent, brain penetrant, next-generation ALK/ROS1 TKI, with high response rates and durable responses, including the brain. However, a significant drawback is the manifestation of neurocognitive adverse events (NCAEs). Despite being generally low-grade in severity, these NCAEs can be physically and mentally disabling. Extensive neurocognitive testing in this group of patients is lacking; therefore we conducted this study. Patients and methodsThis observational prospective study was conducted across 3 Dutch university hospitals. Patients with metastatic NSCLC with an ALK- or ROS1-rearrangement and having an indication to start lorlatinib in daily clinical practice were eligible. The primary endpoints were to identify changes in neurocognitive functioning, measured through neurocognitive assessment at intervals of 2 weeks and 2 months after starting lorlatinib, in comparison to baseline. As a secondary endpoint, the correlation between neurocognitive impairment and self-reported neurocognitive dysfunction was examined. ResultsBetween June 2019 and October 2022, 22 patients were included. Among the various neurocognitive tests administered, only the Hopkins Verbal Learning Test-Revised parts b and c demonstrated a significant and clinically relevant decrease in scoring 2 weeks post initiation of lorlatinib (P = .036 and P = .003, respectively). However, these returned to baseline at the 2-month evaluation. The questionnaires did not result in significantly different outcomes over time. ConclusionLorlatinib treatment did not result in a sustained and significant decline within any of the specified neurocognitive domains.

Genetic Factors and Long-term Treatment-Related Neurocognitive Deficits, Anxiety, and Depression in Childhood Leukemia Survivors: An Exome-Wide Association Study.

An increased risk of neurocognitive deficits, anxiety, and depression has been reported in childhood cancer survivors. We analyzed associations of neurocognitive deficits, as well as anxiety and depression, with common and rare genetic variants derived from whole-exome sequencing data of acute lymphoblastic leukemia (ALL) survivors from the PETALE cohort. In addition, significant associations were assessed using stratified and multivariable analyses. Next, top-ranking common associations were analyzed in an independent SJLIFE replication cohort of ALL survivors. Significant associations were identified in the entire discovery cohort (N = 229) between the AK8 gene and changes in neurocognitive function, whereas PTPRZ1, MUC16, TNRC6C-AS1 were associated with anxiety. Following stratification according to sex, the ZNF382 gene was linked to a neurocognitive deficit in males, whereas APOL2 and C6orf165 were associated with anxiety and EXO5 with depression. Following stratification according to prognostic risk groups, the modulatory effect of rare variants on depression was additionally found in the CYP2W1 and PCMTD1 genes. In the replication SJLIFE cohort (N = 688), the male-specific association in the ZNF382 gene was not significant; however, a P value<0.05 was observed when the entire SJLIFE cohort was analyzed. ZNF382 was significant in males in the combined cohorts as shown by meta-analyses as well as the depression-associated gene EXO5. Further research is needed to confirm whether the current findings, along with other known risk factors, may be valuable in identifying patients at increased risk of these long-term complications. Our results suggest that specific genes may be related to increased neuropsychological consequences.

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.

Longitudinal change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis: a systematic review.

Clinical high risk of psychosis (CHR-P) population has become an attractive area of interest in preventing transitions to psychosis. The consequences of developing a psychotic disorder may be worse in cases of early onset. Thus, childhood and adolescence represent a critical developmental window, where opportunities to gain social and adaptive abilities depend on the individuals' neurocognitive performance. There have been previous syntheses of the evidence regarding neurocognitive functioning in CHR-P individuals and its longitudinal changes. However, there has been less focus on children and adolescents at CHR-P. A multistep literature search was performed from database inception until July 15th, 2022. PRIMSA/MOOSE compliant systematic review and PROSPERO protocol were used to identify studies reporting on longitudinal changes in neurocognitive functioning in children and adolescents (mean age of sample ≤ 18years) at CHR-P and matched healthy control (HC) group. A systematic review of identified studies was then undertaken. Three articles were included, resulting in a total sample size of 151 CHR-P patients [mean (SD) age, 16.48 (2.41) years; 32.45% female] and 64 HC individuals [mean (SD) age, 16.79 (2.38) years; 42.18% female]. CHR-P individuals had worse outcomes in verbal learning, sustained attention and executive functioning domains compared to HC. Individuals taking antidepressants had better outcomes in verbal learning in contrast with those taking antipsychotics. In children and adolescents, neurocognition may be already impaired before the psychosis onset, and remains stable during the transition to psychosis. Further study should be performed to obtain more robust evidence.

Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression

IntroductionKetamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response. MethodsPatients with TRD (N = 66; 30 M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg). Neurocognitive function and depressive symptoms were assessed at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks following end of treatment. Mixed effect models tested for changes in seven neurocognitive domains and antidepressant response, with post-hoc pairwise comparisons between timepoints, including follow-up. Relationships between change in neurocognitive function and antidepressant response over the course of treatment were tested with Pearson's correlation and mediation analyses. Associations between baseline neurocognitive performance and antidepressant response were tested with Pearson's correlation. ResultsSignificant improvements in inhibition, working memory, processing speed, and overall fluid cognition were observed after the first and fourth ketamine infusion. Improvements in processing speed and overall fluid cognition persisted through follow-up. Significant improvements in depressive symptoms reverted towards baseline at follow-up. Baseline working memory and change in inhibition were moderately correlated with antidepressant response, however, improvements in neurocognitive performance were statistically independent from antidepressant response. ConclusionAntidepressant ketamine leads to improved neurocognitive function, which persist for at least 5 weeks. Neurocognitive improvements observed appear independent of antidepressant response, suggesting ketamine may target overlapping but distinct functional brain systems.LimitationsResearch investigating repeated serial ketamine treatments is important to determine cognitive safety. This study is a naturalistic design and does not include placebo.

339. Changes in Neurocognitive Function Following Sub-Anesthetic Single and Serial Ketamine Infusions in Treatment Resistant Depression

339. Changes in Neurocognitive Function Following Sub-Anesthetic Single and Serial Ketamine Infusions in Treatment Resistant Depression

Association between objective neurocognitive functioning and neurocognitive complaints in recurrent high-grade glioma: Longitudinal evidence of cognitive awareness from EORTC brain tumour trials

BackgroundPatients’ reduced awareness of neurocognitive functioning (NCF) may negatively affect the reliability of patient-reported outcomes (PROs) and clinical decision-making. This study evaluated cognitive awareness, defined as the association between NCF and neurocognitive complaints, over the disease course of patients with recurrent high-grade glioma (HGG). MethodsWe assessed NCF using the EORTC core clinical trial battery and neurocognitive complaints using the Medical Outcome Study questionnaire. Patients were categorised as impaired or intact, based on their neurocognitive performance. Spearman’s rank correlations were calculated between NCF and neurocognitive complaints at baseline and each 12 weeks, until 36. The association between changes in NCF and neurocognitive complaints scores between these follow-up assessments was determined using Pearson’s correlation. ResultsA total of 546 patients were included. Neurocognitively impaired patients (n = 437) had more neurocognitive complaints (range: 10.51 [p < 0.001] to 13.34 [p = 0.001]) than intact patients (n = 109) at baseline, at 12 and 24 weeks. In intact patients, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.202, p = 0.036), while in impaired patients correlations were more frequently found in various domains and time points (range: 0.164 [p = 0.001] to 0.334 [p = 0.011]). Over the disease course, NCF and neurocognitive complaints were correlated for only one domain at baseline (0.357, p = 0.014) in intact patients while in impaired patients they were correlated for more domains and time points (range: 0.222 [p < 0.001] to 0.366 [p < 0.001]). ConclusionNeurocognitively impaired patients with recurrent HGG are aware of their neurocognitive limitations at study entry and during follow-up, which should be considered in clinical decision-making and when interpreting PRO results.

Design Considerations for the Attenuation of Translational and Rotational Accelerations in American Football Helmets.

Participants in American football experience repetitive head impacts that induce negative changes in neurocognitive function over the course of a single season. This study aimed to quantify the transfer function connecting the force input to the measured output acceleration of the helmet system to provide a comparison of the impact attenuation of various modern American football helmets. Impact mitigation varied considerably between helmet models and with location for each helmet model. The current data indicate that helmet mass is a key variable driving force attenuation, however flexible helmet shells, helmet shell cutouts, and more compliant padding can improve energy absorption.

Feasibility of serial neurocognitive assessment using Cogstate during and after therapy for childhood leukemia.

Neurocognitive impairment is frequently observed among survivors of childhood acute lymphoblastic leukemia (ALL) within the domains of attention, working memory, processing speed, executive functioning, and learning and memory. However, few studies have characterized the trajectory of treatment-induced changes in neurocognitive function beginning in the first months of treatment, to test whether early changes predict impairment among survivors. If correct, we hypothesize that those children who are most susceptible to early impairment would be ideal subjects for clinical trials testing interventions designed to protect against treatment-related neurocognitive decline. In this pilot study, we prospectively assessed neurocognitive functioning (attention, working memory, executive function, visual learning, and processing speed), using the Cogstate computerized battery at six time points during the 2years of chemotherapy treatment and 1-year post-treatment (Dana-Farber Cancer Institute ALL Consortium protocol 11-001; NCT01574274). Forty-three patients with ALL consented to serial neurocognitive testing. Of the 31 participants who remained on study through the final time point, 1year after completion of chemotherapy, 28 (90%) completed at least five of six planned Cogstate testing time points. Performance and completion checks indicated a high tolerability (≥ 88%) for all subtests. One year after completion of treatment, 10 of 29 patients (34%) exhibited neurocognitive function more than 2 standard deviations below age-matched norms on one or more Cogstate subtests. Serial collection of neurocognitive data (within a month of diagnosis with ALL, during therapy, and 1-year post-treatment) is feasible and can be informative for evaluating treatment-related neurocognitive impairment.

PROLONGED NIGHTLY FASTING AMONG OLDER ADULTS: A PILOT STUDY EXPLORING CHANGES IN COGNITIVE FUNCTION

Abstract Aging is significantly associated with cognitive decline. A growing number of US adults ages ≥ 65 years have neurocognitive impairment resulting in compromised immediate and/or long-term health outcomes. Interventions to mitigate cognitive decline and promote healthy aging are needed. Research in intermittent fasting (IF) suggests positive health outcomes related to improvements in circadian rhythm and metabolism, which influence cognition. IF regimens may therefore result in improved neurocognitive health. We conducted an IF single-group, pre/post pilot study to explore changes in neurocognitive. Older adults (≥65 years of age; Nf18) with self-reported memory decline engaged in an 8-week, remotely-delivered, prolonged nightly fasting (PNF) intervention (14-hour nightly fasting, 10-hour daytime eating window). Our primary exploratory outcome was 8-week change in neurocognitive function assessed via composite score of the Memory and Attention Phone Screener (MAPS). Trends in outcome change were assessed with paired t-tests. Participants were mean age 69.7 years, non-Hispanic White, predominantly female (94%), married (50%), and employed (65%). Completion defined as percentage of participants that completed the intervention from those that started the intervention; completion rate was 90%. Paired t-test indicated a significant increase in scores on a neurocognitive screen (MAPS) pre/post-intervention (p=0.02) with a medium effect size (Cohen’s d=0.58). Findings suggest that PNF, a type of IF regimen targeted to align food intake with circadian rhythms, may significantly improve neurocognitive function among older adults with self-reported memory decline. These promising pilot results suggest a need for fully-powered, randomized controlled trials to test the efficacy of this non-pharmacological, low cost-to-burden ratio intervention.

Attention problems and off-topic verbosity among young adult and older adult age cohorts

Off-topic verbosity refers to tangential discourse with excessive and irrelevant information. Previous research suggests that age-related increases in off-topic verbosity may be due to underlying changes in neurocognitive functioning. The purpose of this study was to investigate relationships between attention problems and off-topic verbosity. Young adults (n = 63) and older adults (n = 82) were administered a continuous performance test and provided speech samples, which were transcribed and rated for tangentiality, egocentrism, and quantity of speech. Overall, results found that attention problems were associated with greater tangentiality among older adults, but among young adults more attention problems were associated with lower quantity of speech. Attention problems may affect young adults’ and older adult’s speech in different ways, possibly reflecting differences in neurocognitive functioning or communication goals.

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.

Neurocognitive Function Changes Following Kidney Transplant: A Prospective Study

Patients with advanced kidney disease are at risk for cognitive impairment, which may persist after kidney transplantation. We sought to understand changes in neurocognitive function domains utilizing comprehensive cognitive assessments. Prospective cohort study. Single-center study of patients undergoing kidney transplantation. Kidney transplantation. Changes in neurocognitive function as measured by the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Parts A and B (TRAIL A and B) before transplantation (baseline) and compared to 3 months and 12 months posttransplant. Wilcoxon signed-rank and linear mixed effect models were utilized to assess changes in neurocognitive scores at 3 months and 12 months compared to baseline. Thirty-two patients were included with a mean age of 45 years, 47% female, 85% White, and 62% with at least some college education. Hypertension and diabetes were etiologies of kidney disease in 31% and 25% of patients, respectively. Baseline RBANS and TRAIL A and B scores averaged 84.7±14, 40.4±9.9, and 41±11.5, respectively. Although there were posttransplant improvements in immediate and delayed memory at 3 months, these were not sustained at 12 months. There were no significant differences from baseline at 3 months and 12 months in RBANS index scores for language, visuospatial/constructional abilities, and attention. Compared to baseline, TRAIL A scores were not significantly different at 3 months but were significantly improved at 12 months, whereas TRAIL B scores improved significantly at both 3 months and 12 months. Single-center design and small sample size. Utilizing comprehensive cognitive assessments, we found improvements in attention and executive function in the first posttransplant year as measured by TRAIL A and B. However, there was no significant change in global cognition as measured by RBANS. These findings identify cognitive domains for potential intervention in the posttransplant population.

Abstract 14749: Assessment for Neurocognitive Change After Catheter Ablation for Atrial Fibrillation

Introduction: Several studies have been conducted to evaluate the neurocognitive effects of catheter ablation for atrial fibrillation. However, these studies have found mixed results. Theoretically, silent peri-procedural stroke might yield a worsening of neurocognitive function, though normalization of heart rhythms might yield improvement. The purpose of this study was to prospectively follow patients after catheter-ablation for paroxysmal or persistent atrial fibrillation with serial telephone-based Montreal Cognitive Assessments (t-MoCA) over 6 months to evaluate for changes in neurocognitive function. Hypothesis: No change in t-MoCA scores between baseline and 1-month, 3-months, and 6-months after catheter ablation for atrial fibrillation. Methods: All consenting patients who underwent first time or redo catheter ablation for atrial fibrillation (with either radiofrequency- or cryo-ablation) between January 2021 and May 2022 were enrolled in the study. A t-MoCA was conducted to measure cognitive function at baseline, 1 month, 3 months, and 6 months from the date of catheter ablation. Only patients who completed at least 1 month of follow-up were included for analysis. Paired t-tests and one-way ANOVA were used to assess for significant differences in t-MoCA scores. Results: 42 patients met criteria for analysis. Paired two-tailed t-test values at 1-month, 3-months, and 6-months demonstrated an increase in t-MoCA score by 2.17 (n=42, p = 0.036), 3.08 (n=27, p = 0.005), and 3.06 (n=24, p = 0.006) respectively when compared to baseline. One-way ANOVA testing showed no significant differences between the 1-month, 3-month, and 6-month scores (p = 0.73). Conclusions: Patients undergoing first time or redo catheter ablation for atrial fibrillation had significant improvement in t-MoCA scores at 1-month, 3-months, and 6-months post-ablation. The improvement seen at 1-month was sustained throughout the 6-months of follow-up. Further long-term assessment is needed to determine if this effect persists over a longer period of time and to potentially correlate these findings with post-ablation atrial fibrillation recurrence.