Cognitive Speed Research Articles

Abstract P216: Speed-Accuracy Tradeoffs During Cognitive and Upper-Limb Horizontal Movement Tasks in Chronic Strokes

Objectives: This study investigated cognitive-motor interference on the relationship of speed and accuracy during a cognitive and upper-limb motor dual task. Method: Nine stroke patients (56.5±7.3 years; M:9) participated in a series of cognitive-motor dual tasks. A subject with chronic stroke was seated with paretic hand fastened on the handle and then one of five motor tasks was provided (Figure 1A). Visual feedback in a front screen was synchronized as the handle cursor moves within the movement trajectory with two difficulty levels (5cm or 10cm). In a dual task, a cognitive task, Serial Seven(S7), was concurrently provided with a randomly chosen number at the onset of the motor task by a test administrator.Figure 1 Cognitive-Motor dual task setup (left up) and trajectory shapes (Diagonoal; Mediolateral; Anteroposterior; Cross; Circle) and level of difficulties (Easy 10cm or Hard 5cm) in motor tasks. The motor speed and accuracy and the cognitive speed and accuracy were evaluated during one-minute trial time. Pearson-correlation coefficients evaluated outcome relationship of the speed and accuracy in single or cognitive-motor dual tasks with the significance level 0.05 using a commercial statistics package (SPSS ver 22, Chicago IL,US). Results: There were significant positive correlation between single and dual motor speeds ( Easy :R 2 =0.678,p<0.001; Hard : R 2 =0.714,p<0.001) and significant negative correlationbetween single motor speed and dual cognitive speed ( Easy : R 2 =0.661,p<0.001; Hard :R 2 =0.6523,p<0.001) (Figure 1B) Conclusions: There were significant correlations between the upper-limb horizontal movements with visual feedback and S7 cognitive task. This study may provide useful information on upper-limb motor robotic therapies using 2D horizontal upper-limb movements.

The Association Between Cognitive Deficits and Clinical Characteristic in First-Episode Drug Naïve Patients With Schizophrenia.

Background: Schizophrenia is a severe mental disease which characterized by positive symptom, negative symptom, general pathology syndrome and cognitive deficits. In recent years, many studies have investigated the relationship between cognitive deficits and clinical characteristics in schizophrenia, but relatively few studies have been performed on first-episode drug-naïve patients.Methods: Eighty seven first-episode drug-naïve schizophrenia patients were assessed for positive symptom, negative symptom, general pathology symptom and cognitive deficits from the Positive and Negative Symptom Scale and MATRICS Consensus Cognitive Battery. Psychotics depression were assessed using the Calgary depressing scale for schizophrenia. The relationship between clinical characteristics and cognitive deficits were assessed using correlation analysis and linear regression analysis.Results: The prevalence of cognitive deficits among the patients in our study was 85.1% (74/87) which was much higher than that in the general population. According to correlation analysis, negative symptom was negatively correlated with speed of processing and social cognition, and general pathology showed a negative correlation with attention/vigilance. In addition, a positive correlation was found between age and speed of processing. No correlation was found between cognitive deficits and positive symptom.Conclusions: This study confirmed that negative symptom is negatively related with some domains of cognitive function in first-episode drug naïve schizophrenia patients.Trail Registration: NCT03451734. Registered March 2, 2018 (retrospectively registered).

Effects of head-down tilt bed rest plus elevated CO2 on cognitive performance.

Microgravity and elevated CO2 levels are two important environmental spaceflight stressors that can adversely affect astronaut cognitive performance and jeopardize mission success. This study investigated the effects of 6° head-down tilt bed rest (HDBR) with (n = 11 participants, 30-day HDBR) and without (n = 8 participants, 60-day HDBR) elevated ambient (3.73 mmHg) CO2 concentrations on cognitive performance. Participants of both groups performed all 10 tests of NASA's Cognition battery and a brief alertness and mood survey repeatedly before, during, and after the HDBR period. Test scores were adjusted for practice and stimulus set effects. Concentrating on the first 30 days of HDBR, a modest but statistically significant slowing across a range of cognitive domains was found in both groups (controls: -0.37 SD; 95% CI -0.48, -0.27; adjusted P < 0.0001; CO2: -0.25 SD; 95% CI -0.34, -0.16; adjusted P < 0.001), most prominently for sensorimotor speed. These changes were observed early during HDBR and did not further deteriorate or improve with increasing time in HDBR. The study found similar cognitive effects of HDBR irrespective of CO2 levels, suggesting that elevated CO2 neither ameliorated nor worsened the HDBR effects. In both groups, cognitive performance after 15 days of recovery was statistically indistinguishable from pre-HDBR performance. However, subjects undergoing 60 days of HDBR rated themselves as feeling more sleepy, tired, physically exhausted, stressed, and unhealthy during recovery compared to their 30-day counterparts.NEW AND NOTEWORTHY This study investigated the effects of prolonged head-down tilt bed rest with and without elevated (3.73 mmHg) levels of ambient CO2 on cognitive performance across a range of cognitive domains and is one of the few studies investigating combined effects of environmental stressors prevalent in spaceflight. The study showed moderate declines in cognitive speed induced by head-down tilt bed rest and suggests that exposure to elevated levels of ambient CO2 did not modify this effect.

Job Strain and Trajectories of Cognitive Change Before and After Retirement.

ObjectivesWe examined associations between job strain and trajectories of change in cognitive functioning (general cognitive ability plus verbal, spatial, memory, and speed domains) before and after retirement.MethodsData on indicators of job strain, retirement age, and cognitive factors were available from 307 members of the Swedish Adoption/Twin Study of Aging. Participants were followed up for up to 27 years (mean = 15.4, SD = 8.5).ResultsIn growth curve analyses controlling for age, sex, education, depressive symptoms, cardiovascular health, and twinness, greater job strain was associated with general cognitive ability (estimate = −1.33, p = .002), worse memory (estimate = −1.22, p = .007), speed (estimate = −1.11, p = .012), and spatial ability (estimate = −0.96, p = .043) at retirement. Greater job strain was also associated with less improvement in general cognitive ability before retirement and a somewhat slower decline after retirement. The sex-stratified analyses showed that the smaller gains of general cognitive ability before retirement (estimate = −1.09, p = .005) were only observed in women. Domain-specific analyses revealed that greater job strain was associated with less improvement in spatial (estimate = −1.35, p = .010) and verbal (estimate = −0.64, p = .047) ability before retirement in women and a slower decline in memory after retirement in women (estimate = 0.85, p = .008) and men (estimate = 1.12, p = .013). Neither preretirement nor postretirement speed was affected significantly by job strain.DiscussionGreater job strain may have a negative influence on overall cognitive functioning prior to and at retirement, while interrupting exposure to job strain (postretirement) may slow the rate of cognitive aging. Reducing the level of stress at work should be seen as a potential target for intervention to improve cognitive aging outcomes.

Long-Lasting Cognitive Abnormalities after COVID-19.

Considering the mechanisms capable of causing brain alterations in COVID-19, we aimed to study the occurrence of cognitive abnormalities in the months following hospital discharge. We recruited 38 (aged 22–74 years; 27 males) patients hospitalized for complications of SARS-CoV-2 infection in nonintensive COVID units. Participants underwent neuropsychological testing about 5 months after hospital discharge. Of all patients, 42.1% had processing speed deficits, while 26.3% showed delayed verbal recall deficits. Twenty-one percent presented with deficits in both processing speed and verbal memory. Bivariate analysis revealed a positive correlation between the lowest arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) (P/F) ratio during hospitalization and verbal memory consolidation performance (SRT-LTS score, r = 0.404, p = 0.027), as well as a positive correlation between SpO2 levels upon hospital arrival and delayed verbal recall performance (SRT-D score, rs = 0.373, p = 0.042). Acute respiratory distress syndrome (ARDS) during hospitalization was associated with worse verbal memory performance (ARDS vs. no ARDS: SRT-LTS mean score = 30.63 ± 13.33 vs. 44.50 ± 13.16, p = 0.007; SRT-D mean score = 5.95 ± 2.56 vs. 8.10 ± 2.62, p = 0.029). Cognitive abnormalities can frequently be found in COVID-19 patients 5 months after hospital discharge. Increased fatigability, deficits of concentration and memory, and overall decreased cognitive speed months after hospital discharge can interfere with work and daily activities.

Performance in complex life situations: effects of age, cognition, and walking speed in virtual versus real life environments

BackgroundVirtual reality (VR) enables objective and accurate measurement of behavior in ecologically valid and safe environments, while controlling the delivery of stimuli and maintaining standardized measurement protocols. Despite this potential, studies that compare virtual and real-world performance of complex daily activities are scarce. This study aimed to compare cognitive strategies and gait characteristics of young and older healthy adults as they engaged in a complex task while navigating in a real shopping mall and a high-fidelity virtual replica of the mall.MethodsSeventeen older adults (mean (SD) age = 71.2 (5.6) years, 64% males) and 17 young adults (26.7 (3.7) years, 35% males) participated. In two separate sessions they performed the Multiple Errands Test (MET) in a real-world mall or the Virtual MET (VMET) in the virtual environment. The real-world environment was a small shopping area and the virtual environment was created within the CAREN™ (Computer Assisted Rehabilitation Environment) Integrated Reality System. The performance of the task was assessed using motor and physiological measures (gait parameters and heart rate), MET or VMET time and score, and navigation efficiency (cognitive performance and strategy). Between (age groups) and within (environment) differences were analyzed with ANOVA repeated measures.ResultsThere were no significant age effects for any of the gait parameters but there were significant environment effects such that both age groups walked faster (F(1,32) = 154.96, p < 0.0001) with higher step lengths (F(1,32) = 86.36, p < 0.0001), had lower spatial and temporal gait variability (F(1,32) = 95.71–36.06, p < 0.0001) and lower heart rate (F(1,32) = 13.40, p < 0.01) in the real-world. There were significant age effects for MET/VMET scores (F(1,32) = 19.77, p < 0.0001) and total time (F(1,32) = 11.74, p < 0.05) indicating better performance of the younger group, and a significant environment effect for navigation efficiency (F(1,32) = 7.6, p < 0.01) that was more efficient in the virtual environment.ConclusionsThis comprehensive, ecological approach in the measurement of performance during tasks reminiscent of complex life situations showed the strengths of using virtual environments in assessing cognitive aspects and limitations of assessing motor aspects of performance. Difficulties by older adults were apparent mainly in the cognitive aspects indicating a need to evaluate them during complex task performance.

Executive Functions and Attention Processes in Adolescents and Young Adults with Intellectual Disability.

(1) Background: We made a comprehensive evaluation of executive functions (EFs) and attention processes in a group of adolescents and young adults with mild intellectual disability (ID). (2) Methods: 27 adolescents and young adults (14 females and 13 males) with ID, aged between 15.1 and 23 years (M = 17.4; SD = 2.04), were compared to a control group free of cognitive problems and individually matched for gender and age. (3) Results: As for EFs, individuals with ID were severely impaired on all subtests of the Behavioral Assessment of Dysexecutive Syndrome (BADS) battery. However, we also found appreciable individual differences, with eight individuals (approximately 30%) scoring within normal limits. On the attention tests, individuals with ID were not generally slower but presented specific deficits only on some attention tests (i.e., Choice Reaction Times, Color Naming and Color–Word Interference, and Shifting of Attention for Verbal and for Visual Targets).The role of a global factor (i.e., cognitive speed) was modest in contributing to the group differences; i.e., when present, group differences were selectively associated with specific task manipulations, not global differences in cognitive speed. (4) Conclusions: The study confirmed large group differences in EFs; deficits in attentional processing were more specific and occurred primarily in tasks taxing the selective dimension of attention, with performance on intensive tasks almost entirely spared.

Code Comprehension Confounders: A Study of Intelligence and Personality

Program comprehension is a cognitive psychological process. Accordingly, literature and intuition suggest that a developer's intelligence and personality have an impact on their performance in comprehending source code. Some researchers have made this suggestion in the past when discussing threats to validity of their study results. However, the lack of studies investigating the relationship of intelligence and personality to performance in code comprehension makes scientifically sound reasoning about their influence difficult. We conduct the first large-scale empirical evaluation, a correlational study with undergraduates, to investigate the correlation of intelligence and personality with performance in code comprehension, that is, in this context, with correctness in answering comprehension questions on code snippets. We found that personality traits are unlikely to impact code comprehension performance, at least not when their influence is considered in isolation. Conscientiousness, in combination with other factors, however, explains some of the variance in code comprehension performance. For intelligence, significant small to moderate positive effects on code comprehension performance were found for three of four factors measured, i.e., fluid intelligence, visual perception, and cognitive speed. Crystallized intelligence has a positive but statistically insignificant effect on code comprehension performance. According to our results, several intelligence facets as well as the personality trait conscientiousness are potential confounders that should not be neglected in code comprehension studies of individual performance and should be controlled for via an appropriate study design. We call for the conduct of further studies on the relationship between intelligence and personality with code comprehension, in part because code comprehension involves more facets than we can measure in a single study and because our regression model explains only a small portion of the variance in code comprehension performance.

Supplemental Material for Examining Cognitive Speed and Accuracy Dysfunction in Youth and Young Adults With Pediatric-Onset Multiple Sclerosis Using a Computerized Neurocognitive Battery

Supplemental Material for Examining Cognitive Speed and Accuracy Dysfunction in Youth and Young Adults With Pediatric-Onset Multiple Sclerosis Using a Computerized Neurocognitive Battery

Pythagorean Self Awareness Intervention in Caregivers of Patients with Motor Disabilities.

Caregiving for disabled people is a strenuous task often provided by family members, with adverse repercussions on the caregivers’ health. The aim of this study was to evaluate, for the first time, the effects of a novel cognitive-based stress management technique, the Pythagorean Self-Awareness Intervention (PSAI) on the stress levels and other cognitive and psychological characteristics of non-paid caregivers of patients with motor disability. In this quasi-experimental study, 59 caregivers of first-degree relatives with motor disabilities due to chronic neurological diseases, inpatients at a Rehabilitation Center, in Athens, Greece, were assigned to an intervention (PSAI, n=28) and a control group (received unstructured consultation, n=31). Psychological, cognitive, and sleep-related measurements (Zarit Burden Interview tool, Pittsburgh Sleep Quality Index, Self-Efficacy Scale, Depression, Anxiety and Stress Scale, Symbol Digit Modalities Test, California Verbal Learning Test-II, Brief Visuospatial Memory Test-Revised) were held at baseline and after 8 weeks (at completion of PSAI) in both groups. PSAI was found to decrease caregivers’ stress, depressive symptoms and anxiety and improve their sleep quality, visual memory, self-efficacy, and cognitive speed processing. Future randomized controlled studies are needed to investigate the effects of this novel intervention in larger samples of caregivers.

Reader Response: Simple MRI Score Aids Prediction of Dementia in Cerebral Small Vessel Disease.

I read with interest the article by Amin Al Olama et al.1 that used a simple small vessel disease (SVD) score (0–3) from rapid visual assessment of clinical MRI scans to predict the risk of cognitive decline and dementia in a pooled analysis of 3 cohorts. They found that a simple SVD score could be more valuable to predict future dementia risk.1 This work would be greatly helpful for our clinicians to measure the SVD cases who will progress to dementia just by using simple and available routine clinical MRI scans. However, there are still some issues that should be addressed. First, as one of the most important biomarkers of SVD, enlarged perivascular spaces (ePVS) were not included in this simple SVD score, which may be due to the finding that ePVS was not associated with cognitive dysfunction in a recent meta-analysis of 5 cross-sectional studies.2 However, whether ePVS contributes to cognitive decline should be further confirmed in longitudinal studies. As a result, it should be with caution that a conclusion be made that ePVS is not associated with cognitive decline with the evidence from cross-sectional studies.3 Second, there were great heterogeneities in the above 3 different studies by using a battery of neuropsychological tests such as global cognition, executive function, and processing speed.2 Third, different study populations, different follow-up periods, different dementia diagnostic criteria, the heterogeneity of SVD lesions, and large variability in clinical symptoms among patients with SVD all contributed to some selection bias or heterogeneities. As a result, as a global rather than a focal disease, the combined structural and functional connectivities to explore how network disruption by SVD can lead to cognitive deficits and its underlying compensatory mechanisms could be more convincing and promising.4 Network disruption may have a central role in the pathogenesis of cognitive decline and dementia in SVD.5,6

Associations of cannabis use disorder with cognition, brain structure, and brain function in African Americans.

Although previous studies have highlighted associations of cannabis use with cognition and brain morphometry, critical questions remain with regard to the association between cannabis use and brain structural and functional connectivity. In a cross‐sectional community sample of 205 African Americans (age 18–70) we tested for associations of cannabis use disorder (CUD, n = 57) with multi‐domain cognitive measures and structural, diffusion, and resting state brain‐imaging phenotypes. Post hoc model evidence was computed with Bayes factors (BF) and posterior probabilities of association (PPA) to account for multiple testing. General cognitive functioning, verbal intelligence, verbal memory, working memory, and motor speed were lower in the CUD group compared with non‐users (p < .011; 1.9 < BF < 3,217). CUD was associated with altered functional connectivity in a network comprising the motor‐hand region in the superior parietal gyri and the anterior insula (p < .04). These differences were not explained by alcohol, other drug use, or education. No associations with CUD were observed in cortical thickness, cortical surface area, subcortical or cerebellar volumes (0.12 < BF < 1.5), or graph‐theoretical metrics of resting state connectivity (PPA < 0.01). In a large sample collected irrespective of cannabis used to minimize recruitment bias, we confirm the literature on poorer cognitive functioning in CUD, and an absence of volumetric brain differences between CUD and non‐CUD. We did not find evidence for or against a disruption of structural connectivity, whereas we did find localized resting state functional dysconnectivity in CUD. There was sufficient proof, however, that organization of functional connectivity as determined via graph metrics does not differ between CUD and non‐user group.

New Perspectives on Predicting and Modifying Cognition in Older Adulthood

The underlying theme of my research is to advance our understanding of cognitive aging through early detection of cognitive decline and the promotion of positive lifestyle factors. I will present my past and recent work that uses new perspectives to predict and modify cognition with older age, specifically focusing on intraindividual variability in cognitive speed, and lifestyle activity engagement. This includes examining the utility of variability in cognitive speed, usually a predictor of decline, instead as a predictor of cognitive plasticity following activity interventions. Further, the association between activity engagement and later cognitive ability and dementia risk is more complex than first appears. I will present research that looks at critical issues about the activity-cognition relation from a different perspective, including unique frameworks investigating the ideal way to measure activity, and the duration of how long past activity can potentially impact cognition. Finally, I will discuss my future research directions.

Associations Between Smoking and Cognitive Function Among Community-Dwelling U.S. Chinese Older Adults in Chicago

Previous studies on smoking and cognition reported mixed findings. The inconsistent results are partially explained by the fact that they were limited to specific populations and using different cognitive function measurements. This association between smoking and cognition has rarely been studied in the rapidly increasing U.S. Chinese older adults. This study aims to determine if smoking status and smoking amount are associated with global cognition and cognitive domains in U.S. Chinese older adults. Data was extracted PINE. Five cognitive function tests (East Boston Memory Test, East Boston Memory Delayed Recall, Digital Backward test, Symbol digit Modality Test, and MMSE) were used to measure cognitive domains including episodic memory, working memory, and processing speed. Five cognitive tests were converted to z scores and averaged to generate global cognition. Self-reported smoking status was used for generating smoking status and smoking amount (pack-years). Linear regression was used. The results showed that former smokers had lower global cognition (b=-0.111, SE=0.053, p<.05) and perceptual speed (b=-0.185, SE=0.066, p<.01) than never smokers; current smokers had lower global cognition (b=-0.240, SE=0.060, p<.001), working memory (b=-0.340, SE=0.083, p<.001) and perceptual speed (b=-0.370, SE=0.075, p<.001) compared with never smokers. Smoking pack-years is negatively associated with global cognition (b=-0.003, SE=0.001,p<.001), episodic memory (b=-0.005, SE=0.001, p<.001), and perceptual speed (b=-0.004, SE=0.001, p<.001). Findings revealed that among all smokers, current smokers had the worst cognition and heavier smoking was associated with worse cognition. Policymakers could take measures in lowering smoking amount among U.S. Chinese older adults to protect their cognition.

More Energy and Less Fatigue: Implications for Successful Brain Aging

Higher energy and lower fatigue are intuitively important to live independent, active lives. However, little is known about the relation between brain health, energy, and fatigue in older adults. From a neurobiological standpoint, energy and fatigue appear to rely on distinct, albeit overlapping brain networks, but most evidence is from patients with neurodegenerative conditions. These relations have not been fully examined in community older adults. In this symposium, we first present an overview of the neurobiology underlying fatigability and energy states. We will then present original unpublished data on brain health, fatigability, and energy from four well-established epidemiological studies of aging: Osteoporotic Fractures in Men Study (MrOS), Long Life Family Study (LLFS), Baltimore Longitudinal Study of Aging (BLSA), and the Health Aging Body Composition Study (Health ABC). Specifically, Ms. Allen will explore whether personality traits are related to perceived mental fatigability in MrOS. Using LLFS data, Ms. Gmelin will examine whether perceived physical fatigability is associated with global cognition, verbal fluency, memory and psychomotor speed. Dr. Schrack will share BLSA data showing cross-sectional and longitudinal associations between lower walking efficiency and reduced brain volumes. Dr. Tian will evaluate the neuroimaging signature of perceived energy levels in Health ABC. Taken together, our data indicate that higher energy and lower fatigability likely reflect overlapping but distinct aspects of brain health. The long-term effects of promoting energy and lowering fatigability on dementia should be further studied.

Greater Perceived Physical Fatigability Is Associated with Lower Cognition: The Long Life Family Study

Greater perceived physical fatigability is associated with physical functional decline, but few studies have examined its relation with cognition. Adults ≥60 (mean±SD age 73.7±10.5, 54.7% female, 99.6% white) from the Long Life Family Study (n=2355) completed the Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater fatigability) and a neurocognitive examination. Generalized estimating equations were used to account for family structure. Covariates included age, sex, field center, depressive symptoms (Center for Epidemiological Studies-Depression), education, and self-reported health. Each 1-point greater PFS was associated with lower: (1) global cognition (Mini-Mental Status Exam; β=-0.36,p<.0001), (2) verbal fluency (phonemic: β=-0.09,p=.029 and semantic: β=-0.14,p<.0001), (3) memory (Hopkins Verbal Learning Test-Revised: β=-0.06,p=.037), and (4) psychomotor speed (Digit Symbol Substitution Test: β=-0.10,p<.0001), after covariate adjustment. Greater perceived physical fatigability was significantly associated with lower memory and cognitive function in older adults, and may represent a promising new biomarker of biological aging reflecting declining brain reserve, resilience, and neurodegeneration.

Predictors of Physical Resilience in Older Adults

Physical resilience (PR), which denotes one’s ability to resist functional physical decline, can be operationalized through longitudinal assessments on the Short Physical Performance Battery (SPPB). Dual-task walking (DTW) is predictive of adverse outcomes but its role in predicting incident PR has not been assessed. Herein, we determined whether velocity during Single-Task-Walk (STW) and Dual-Task-Walk (DTW) conditions predicted incident loss of PR and identified moderators of this relationship. Participants were 163 (mean age=75.5; %female=52) non-demented, community-dwelling older adults with baseline SPPB scores of 10-12. At baseline, individuals completed neuropsychological testing, the SPPB and DTW paradigm. Cognitive reserve was evaluated using the Wide Range Achievement Test (WRAT-3) and speed of processing was assessed using the Symbol Digit Modalities Test (SDMT). Individuals with SPPB scores < 10 were categorized as not physically resilient. Those with scores of 10 or higher were categorized as physically resilient. At three-year follow up 75.4% (n=123) of participants remained physically resilient while 24.5% (n=40) lost PR. Binary logistic regression revealed that slower DTW (OR= 0.96, p= 0.033, 95%CI [.926, .997]), but not STW velocity (OR= 1.00, p= 0.861, 95%CI [0.962, 1.048]), was a significant predictor of PR loss. Moreover, moderation analyses revealed that DTW velocity predicted PR loss only among individuals who had lower baseline scores on the WRAT-3 (OR=0.937, p=0.004, 95%CI [.896, .979]) and SDMT (OR=0.949, p=0.018, 95%CI [.909, .991]). We propose that cognitive reserve and speed of processing influenced the utility of DTW velocity in predicting PR loss among community-residing older adults.

Late-Onset Suicide: A Dementia Prodrome?

This study examined whether late-onset (versus early-onset) suicidal behavior is associated with worse cognition. Participants included 278 adults aged 50+ years (56 nonpsychiatric comparison group; 67 nonsuicidal depressed older adults; 63 depressed suicide ideators; and 44 late-onset (55+ years) and 48 early-onset suicide attempters (<55 years). Using a case-control design, this study examined group differences in global cognition, episodic memory, information processing speed, and executive functioning, assessed using the Repeatable Battery of Neuropsychological Status and the Trail Making Test from the Delis-Kaplan Executive Function System. Linear regression was used for data analyses. Both attempter groups displayed worse executive functioning than nonsuicidal depressed older adults. Late-onset attempters additionally displayed poorer global cognition and processing speed than nonsuicidal depressed older adults and poorer memory than early-onset attempters. Late-onset suicidal behavior is associated with worse performance in a broad range of cognitive domains, possibly reflective of a dementia prodrome.

EPEN-25. EXCEPTIONAL CLINICAL AND IMAGING RESPONSE TO TRK-INHIBITION IN A PATIENT WITH SUPRATENTORIAL EPENDYMOMA HARBORING NTRK2 GENE FUSION

BACKGROUNDPatients with metastatic pediatric ependymoma have limited therapeutic options and poor outcomes. Approximately ¾ of supratentorial ependymomas are driven by C11ORF95-RELA fusions, and the remaining by a heterogeneous group of fusion events. We present a six year-old male diagnosed with supratentorial ependymoma with leptomeningeal carcinomatosis harboring an NTRK2-fusion. Local and distant multifocal, intracranial and intraspinal tumor recurrence occurred seven months following gross total resection of the primary lesion and proton beam craniospinal irradiation.METHODSDNA and RNA from FFPE tumor were used for targeted sequencing using an 81-gene fusion panel and 124-gene mutation panel. Separately, capture transcriptome sequencing, exome sequencing, and copy number array were performed as part of the Texas KidsCanSeq study, an NHGRI/NCI-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium project. All sequencing was carried out in CLIA-certified laboratories.RESULTSAn in-frame fusion between 5’ exons 1–3 of KANK1 and 3’ exons 16–21 of NTRK2, predicted to retain the kinase domain, was identified. At tumor recurrence, therapy was initiated with Larotrectinib, an FDA-approved pan-TRK inhibitor. Clinical improvement in cognitive speed, motor strength, and coordination was observed at two weeks with significant tumor response on MRI at two and four months.CONCLUSIONTRK gene fusions have not previously been reported in ependymoma. Further tumor characterization by methylation profiling is underway and will be of diagnostic interest given the apparent discordance between tumor histology and molecular findings. This case highlights the potential impact of clinical genomic analysis for children with CNS tumors.

QOL-28. NEUROCOGNITIVE PROFILE OF PEDIATRIC MEDULLOBLASTOMA PATIENTS PRIOR TO RADIATION THERAPY

Neurocognitive late effects are unfortunately common following treatment for pediatric medulloblastoma. While radiation therapy is an essential component of treatment for most pediatric medulloblastoma patients, it is associated with neurocognitive compromise. Effects include deficits in cognitive speed and performance efficiency, aspects of attention, as well as working memory. Yet long after treatment it is difficult to tease apart relative contributions of other risk factors to neurocognitive functioning beyond radiation. We examined neurocognitive functioning in a sample of pediatric medulloblastoma patients prior to radiation therapy, including investigation of neurocognitive risk factors such as hydrocephalus, presence of posterior fossa syndrome, and duration of neurological symptoms prior to diagnosis. Results indicated that the sample functioned in the average range in terms of overall IQ (n=34, X̅=103). Patients also functioned in the normal range in terms of language-based ability (X̅=106), nonverbal ability (X̅=104), and working memory (X̅=103). However, the sample performed statistically significantly lower than the general population in terms of cognitive speed and efficiency (z=-2.026, p=.043). The sample was also rated by parents as exhibiting more attention problems relative to the general population (z=1.988, p=.047). There was no specific association with hydrocephalus, duration of symptoms, or history of posterior fossa syndrome. Results suggest weaknesses in attention and processing speed may exist in some pediatric medulloblastoma patients prior to radiation therapy secondary to tumor and related complications. Implications for future research are presented, along with difficulties inherent to “baseline” assessment with pediatric brain tumor survivors.