Memory, processing of emotional stimuli, and volume of limbic structures in pediatric-onset multiple sclerosis.

OBJECTIVE: The limbic system is involved in memory and in processing of emotional stimuli. We measured volume of the hippocampus, amygdala, and thalamus, and assessed their relative contribution to episodic memory and emotion identification in POMS. METHOD: Sixty-five POMS participants (Mage = 18.3 ± 3.9 years; 48 female (73.8%)), average disease duration = 3.8 ± 3.8 years) and 76 age- and sex-matched controls (Mage = 18.1 ± 4.6 years; 49 female (64.5%)) completed the Penn Computerized Neurocognitive Battery (PCNB); 59 of 65 POMS participants and 69 out of 76 controls underwent 3 T MRI scanning. We derived age-adjusted Z-scores on accuracy and response time (RT) measures of episodic memory and emotion identification of the PCNB. Magnetic resonance imaging (MRI) volumetrics were normalized using the scaling factor computed by SIENAx. On PCNB tests that differed between groups, we used multiple linear regression to assess relationships between regional brain volumes and either episodic memory or emotion identification outcomes controlling for age, sex, accuracy/RT, and parental education. RESULTS: POMS participants were slower and less accurate than controls on the episodic memory domain but did not differ from controls on emotion outcomes. At the subtest level, POMS participants showed reduced accuracy on Word Memory (p = .002) and slower performance on Face Memory (p = .04) subtests. POMS participants had smaller total and regional brain volumes of the hippocampus, amygdala, and thalamus (p values ≤ 0.01). Collapsing across groups, both hippocampal and thalamic volume were significant predictors of Word Memory accuracy; hippocampal volume (B = 0.24, SE = 0.10, p = .02) was more strongly associated with Word Memory performance than thalamic volume (B = 0.16, SE = 0.05, p = .003), though the estimate with was less precise. CONCLUSIONS: POMS participants showed reduced episodic memory performance compared to controls. Aspects of episodic memory performance were associated with hippocampal and thalamic volume. Emotion identification was intact, despite volume loss in the amygdala.

Examining cognitive speed and accuracy dysfunction in youth and young adults with pediatric-onset multiple sclerosis using a computerized neurocognitive battery.

OBJECTIVE: We evaluated performance on the Penn Computerized Neurocognitive Battery (PCNB), a tool assessing accuracy and response time across four cognitive domains, alongside the Symbol Digit Modalities Test (SDMT), a measure of processing speed commonly used in MS. We determined whether performance decrements are more likely to be detected on measures of accuracy versus response time in pediatric-onset multiple sclerosis (POMS). METHODS: Performance on the SDMT, accuracy on PCNB tests belonging to four domains (executive function, episodic memory, complex cognition, social cognition), and response time on the PCNB were compared for 65 POMS patients (age range: 8-29 years) and 76 healthy controls (HCs) by ANCOVA. Associations between the Overall PCNB score and SDMT were examined for both groups, and their agreement in classifying impairment was assessed using Cohen's kappa. RESULTS: POMS patients (age at testing = 18.3 ± 4.0 years; age at POMS onset = 14.9 ± 2.3 years) demonstrated reduced accuracy relative to HCs on tests of working memory, attention/inhibition, verbal memory, and visuospatial processing, after adjusting for response time (p ≤ .002). Patients demonstrated slower overall response time on the PCNB (p = .003), while group differences on the SDMT did not meet significance (p = .03). Performance on the PCNB and SDMT were correlated (MS: r = 0.43, HC: r = 0.50, both p < .001), however, the degree of agreement for impairment was minimal (k = 0.22, p = .14). CONCLUSION: Specific cognitive deficits exist independently of slowed information processing speed in POMS, and may represent more significant areas of dysfunction. Delineation of accuracy and response time in neuropsychological assessment is important to identify areas of cognitive deficit in POMS. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Consistent Physical Activity and Future Neurocognitive Problems in Adult Survivors of Childhood Cancers: A Report From the Childhood Cancer Survivor Study.

PURPOSE: To investigate longitudinal associations between physical activity (PA) and neurocognitive problems in adult survivors of childhood cancer. METHODS: A total of 12,123 5-year survivors diagnosed between 1970 and 1999 (median [range] age at diagnosis, 7 [0-21] years, time since diagnosis at baseline, 16 [6-30] years) and 720 siblings self-reported PA and neurocognitive problems. PA was collected at baseline, and PA and neurocognitive data were obtained 7 (1-12) years and 12 (9-14) years later. PA consistency was defined as any combination of ≥ 75 minutes of vigorous or 150 minutes of moderate activity per week on all surveys. Multiple linear regressions, conducted separately for CNS and non-CNS survivors, identified associations between PA consistency and neurocognitive outcomes (expected mean, 50; standard deviation [SD], 10). Mediating effects of body mass index (BMI) and chronic health conditions (CHCs) were evaluated. RESULTS: Survivors were less likely than siblings to report consistent PA (28.1% v 33.6%) and more likely to report problems in Task Efficiency (T-scores mean ± SD: siblings, 50.0 ± 0.4; CNS, 61.4 ± 0.4; non-CNS, 53.3 ± 0.3), Emotion Regulation (siblings, 51.4 ± 0.4; CNS, 54.5 ± 0.3; non-CNS 53.4 ± 0.2), and Memory (siblings, 50.8 ± 0.4; CNS, 58.9 ± 0.4; non-CNS, 53.5 ± 0.2; all P < .001). Survivors of CNS cancers (52.8 ± 0.3) also reported poorer Organization than siblings (49.9 ± 0.4; P < .001). After adjusting for age at diagnosis, age at questionnaire, emotional distress, and cancer treatment exposures, consistent PA was associated with fewer neurocognitive problems compared with consistent inactivity for both CNS and non-CNS groups (T-score differences ranging from -7.9 to -2.2) and larger neurocognitive improvements over time (-6.0 to -2.5), all P ≤ .01. BMI and severe CHCs partially mediated the PA-neurocognitive associations, but the mediation effects were small (change in ß ≤ 0.4). CONCLUSION: Adult survivors of childhood cancer who report more consistent PA have fewer neurocognitive problems and larger improvements in these concerns many years after treatment.

Factors associated with health care utilization in pediatric multiple sclerosis.

BACKGROUND: We assessed whether clinical characteristics and health-related quality of life (HRQOL) are independently associated with subsequent hospitalizations and physician visits among children with multiple sclerosis (MS); and whether differences in HRQOL account for differences in physician visits between children with MS, monophasic acquired demyelinating syndromes (ADS) and healthy children. METHODS: We used linked administrative (health) data from Ontario, Canada and data from a prospective cohort study including HRQOL (measured using the PedsQL), age, sex, cognitive function (accuracy and response time as assessed by Penn Neurocognitive Battery), number of relapses, and neurologic abnormalities on examination. We used generalized linear models with generalized estimating equations to examine factors associated with hospitalizations and ambulatory physician visit rates following each HRQOL assessment, adjusting for age, sex, and socioeconomic status. RESULTS: We included 36 children with MS, 43 with monophasic ADS and 43 healthy controls. Among children with MS, more relapses were associated with increased odds of hospitalization (odds ratio 1.59; 1.18-2.14); better cognitive accuracy scores were associated with fewer physician visits (rate ratio [RR] 0.68; 0.47-0.98). Children with MS had higher rates of physician visits than healthy children (RR 1.44; 1.00-2.08), unlike children with a monophasic ADS, but HRQOL scores did not account for these differences. CONCLUSION: Within the MS population, more relapses are associated with increased odds of hospitalization while better cognitive performance is associated with reduced rates of physician visits. Differences in HRQOL do not account for differences in physician visits by children with MS as compared to healthy children.

Enhanced Recruitment During Executive Control Processing in Cognitively Preserved Patients With Pediatric-Onset MS.

OBJECTIVES: Youth and young adults with pediatric-onset multiple sclerosis (MS) are vulnerable to executive dysfunction; however, some patients do not demonstrate functional deficits despite showing abnormalities on structural magnetic resonance imaging (MRI). Cognitively intact adults with MS have shown enhanced activation patterns relative to healthy controls on working memory tasks. We aim to evaluate whether cognitively preserved pediatric-onset MS patients engage compensatory recruitment strategies to facilitate age-normative performance on a task of working memory. METHODS: Twenty cognitively preserved patients (mean age=18.7±2.7 years; 15 female) and 20 age- and sex-matched controls (mean age=18.5±2.9 years; 15 female) underwent neuropsychological testing and 3.0 Tesla MRI, including structural and functional acquisitions. Patterns of activation during the Alphaspan task, a working memory paradigm with two levels of executive control demand, were examined via whole-brain and region of interest (ROI) analyses. RESULTS: Across all participants, lower accuracy and greater activation of regions implicated in working memory were observed during the high demand condition. MS patients demonstrated 0.21 s longer response time than controls. ROI analyses revealed enhanced activation for pediatric-onset MS patients relative to controls in the right middle frontal, left paracingulate, right supramarginal, and left superior parietal gyri during the low executive demand condition, over and above differences in response time. MS patients also demonstrated heightened activation in the right supramarginal gyrus in the high executive demand condition. CONCLUSIONS: Our findings suggest that pediatric-onset MS patients may engage compensatory recruitment strategies during working memory processing. (JINS, 2019, 25, 432-442).

Feasibility of computerized working memory training in individuals with Huntington disease.

OBJECTIVES: Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population. METHODS: Nine patients, aged 26-62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software. RESULTS: Seven of nine patients demonstrated adherence to the training and completed all sessions within the recommended timeframe of 5 weeks. All adherent patients showed improvement on the Cogmed tasks as defined by the Improvement Index (M = 22.17, SD = 8.84, range = 13-36). All adherent patients reported that they found training helpful (n = 7), and almost all felt that their memory improved (n = 6). Participants also expressed that the training was difficult, sometimes frustrating, and time consuming. CONCLUSIONS: This pilot study provides support for feasibility of computerized WM training in early-stage patients with HD. Results suggest that HD patients perceive benefits of intensive WM training, though a full-scale and controlled intervention project is needed to understand the size of the effect and reliability of changes over time. TRIAL REGISTRATION: ClinicalTrials.gov, Registry number NCT02926820.

Implementation of a structured hospital-wide morbidity and mortality rounds model.

IMPORTANCE: There is a paucity of literature on the quality and effectiveness of institutional morbidity & mortality (M&M) rounds processes. OBJECTIVE: We sought to implement and evaluate the effectiveness of a hospital-wide structured M&M rounds model at improving the quality of M&M rounds across multiple specialties. DESIGN, SETTING, PARTICIPANTS: We conducted a prospective interventional study involving 24 clinical groups (1584 physicians) at a tertiary care teaching hospital from January 2013 to June 2015. INTERVENTION: We implemented the published Ottowa M&M Model (OM3): appropriate case selection, cognitive/system issues analyses, interprofessional participation, dissemination of lessons and effector mechanisms. MAIN OUTCOMES AND MEASURES: We created an OM3 scoring index reflecting these elements to measure the quality of M&M rounds. Secondary outcomes include explicit discussions of cognitive/system issues and resultant action items. RESULTS: OM3 scores for all participating groups improved significantly from a median of 12.0/24 (95% CI 10 to 14) to 20.0/24 (95% CI 18 to 21). An increased frequency of in-rounds discussion around cognitive biases (pre 154/417 (37%), post 256/466 (55%); p<0.05) and system issues (pre 175/417 (42%), post 259/466 (62%); p<0.05) were reported by participants via online surveys postintervention, while in-person surveys throughout the intervention period demonstrated even higher frequencies (cognitive biases 1222/1437 (85%); system issues 1250/1437 (87%)). We found 45 action items resulting directly from M&M rounds postintervention, compared with none preintervention. CONCLUSIONS AND RELEVANCE: Implementation of a structured model enhanced the quality of M&M rounds with demonstrable policy improvements hospital wide. The OM3 can be feasibly implemented at other hospitals to effectively improve quality of M&M rounds across different specialties.

A prospective study of grey matter and cognitive function alterations in chemotherapy-treated breast cancer patients.

PURPOSE: Subsequent to chemotherapy treatment, breast cancer patients often report a decline in cognitive functioning that can adversely impact many aspects of their lives. Evidence has mounted in recent years indicating that a portion of breast cancer survivors who have undergone chemotherapy display reduced performance on objective measures of cognitive functioning relative to comparison groups. Neurophysiological support for chemotherapy-related cognitive impairment has been accumulating due to an increase in neuroimaging studies in this field; however, longitudinal studies are limited and have not examined the relationship between structural grey matter alterations and neuropsychological performance. The aim of this study was to extend the cancer-cognition literature by investigating the association between grey matter attenuation and objectively measured cognitive functioning in chemotherapy-treated breast cancer patients. METHODS: Female breast cancer patients (n = 19) underwent magnetic resonance imaging after surgery but before commencing chemotherapy, one month following treatment, and one year after treatment completion. Individually matched controls (n = 19) underwent imaging at similar intervals. All participants underwent a comprehensive neuropsychological battery comprising four cognitive domains at these same time points. Longitudinal grey matter changes were investigated using voxel-based morphometry. RESULTS: One month following chemotherapy, patients had distributed grey matter volume reductions. One year after treatment, a partial recovery was observed with alterations persisting predominantly in frontal and temporal regions. This course was not observed in the healthy comparison group. Processing speed followed a similar trajectory within the patient group, with poorest scores obtained one month following treatment and some improvement evident one year post-treatment. CONCLUSION: This study provides further credence to patient claims of altered cognitive functioning subsequent to chemotherapy treatment.