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

PURPOSE: 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. METHODS: 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 2 years of chemotherapy treatment and 1-year post-treatment (Dana-Farber Cancer Institute ALL Consortium protocol 11-001; NCT01574274). RESULTS: Forty-three patients with ALL consented to serial neurocognitive testing. Of the 31 participants who remained on study through the final time point, 1 year 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. CONCLUSIONS: 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.

Validation of a digit symbol substitution test for use in supervised and unsupervised assessment in mild Alzheimer's disease.

INTRODUCTION: The Digit-Symbol-Substitution Test (DSST) is used widely in neuropsychological investigations of Alzheimer's Disease (AD). A computerized version of this paradigm, the DSST-Meds, utilizes medicine-date pairings and has been developed for administration in both supervised and unsupervised environments. This study determined the utility and validity of the DSST-Meds for measuring cognitive dysfunction in early AD. METHOD: Performance on the DSST-Meds was compared to performance on the WAIS Coding test, and a computerized digit symbol coding test (DSST-Symbols). The first study compared supervised performance on the three DSSTs versions in cognitively unimpaired (CU) adults (n = 104). The second compared supervised DSST performance between CU (n = 60) and mild-symptomatic AD (mild-AD, n = 79) groups. The third study compared performance on the DSST-Meds between unsupervised (n= 621) and supervised settings. RESULTS: In Study 1, DSST-Meds accuracy showed high correlations with the DSST-Symbols accuracy (r = 0.81) and WAIS-Coding accuracy (r = 0.68). In Study 2, when compared to CU adults, the mild-AD group showed lower accuracy on all three DSSTs (Cohen's d ranging between 1.39 and 2.56) and DSST-Meds accuracy was correlated moderately with Mini-Mental State Examination scores (r = 0.44, p < .001). Study 3 observed no difference in DSST-meds accuracy between supervised and unsupervised administrations. CONCLUSION: The DSST-Meds showed good construct and criterion validity when used in both supervised and unsupervised contexts and provided a strong foundation to investigate the utility of the DSST in groups with low familiarity to neuropsychological assessment.

A Paradox in Digital Memory Assessment: Increased Sensitivity With Reduced Difficulty.

The One Card Learning Test (OCL80) from the Cogstate Brief Battery-a digital cognitive test used both in-person and remotely in clinical trials and in healthcare contexts to inform health decisions-has shown high sensitivity to changes in memory in early Alzheimer's disease (AD). However, recent studies suggest that OCL sensitivity to memory impairment in symptomatic AD is not as strong as that for other standardized assessments of memory. This study aimed to improve the sensitivity of the OCL80 to AD-related memory impairment by reducing the test difficultly (i.e., OCL48). Experiment 1 showed performance in healthy adults improved on the OCL48 while the pattern separation operations that constrain performance on the OCL80 were retained. Experiment 2 showed repeated administration of the OCL48 at short retest intervals did not induce ceiling or practice effects. Experiment 3 showed that the sensitivity of the OCL48 to AD-related memory impairment (Glass's Δ = 3.11) was much greater than the sensitivity of the OCL80 (Glass's Δ = 1.94). Experiment 4 used data from a large group of cognitively normal older adults to calibrate performance scores between the OCL80 and OCL48 using equipercentile equating. Together these results showed the OCL48 to be a valid and reliable test of learning with greater sensitivity to memory impairment in AD than the OCL80.

Unsupervised assessment of cognition in the Healthy Brain Project: Implications for web-based registries of individuals at risk for Alzheimer's disease.

INTRODUCTION: Web-based platforms are used increasingly to assess cognitive function in unsupervised settings. The utility of cognitive data arising from unsupervised assessments remains unclear. We examined the acceptability, usability, and validity of unsupervised cognitive testing in middle-aged adults enrolled in the Healthy Brain Project. METHODS: A total of 1594 participants completed unsupervised assessments of the Cogstate Brief Battery. Acceptability was defined by the amount of missing data, and usability by examining error of test performance and the time taken to read task instructions and complete tests (learnability). RESULTS: Overall, we observed high acceptability (98% complete data) and high usability (95% met criteria for low error rates and high learnability). Test validity was confirmed by observation of expected inverse relationships between performance and increasing test difficulty and age. CONCLUSION: Consideration of test design paired with acceptability and usability criteria can provide valid indices of cognition in the unsupervised settings used to develop registries of individuals at risk for Alzheimer's disease.

Necessity of technicians for computerized neuropsychological assessment devices in multiple sclerosis.

OBJECTIVE: Determine the influence of technician supervision on computer-administered cognitive tests in multiple sclerosis (MS). METHODS: Eighty MS patients underwent assessment using the CogState Brief Battery (CSBB) and the Cleveland Clinic Cognitive Battery (C3B). Each was administered twice, once with a technician guiding assessment, and once with technician-absent. Twenty-eight healthy controls were also evaluated. RESULTS: The influence of technician guidance was not statistically significant for group means on either test. For CSBB, administration problems were more common in the technician-absent condition. CONCLUSION: In this MS sample, reliable and valid test results were obtained from computer-assisted cognitive testing without technician guidance.

Computerized assessment of cognitive impairment among children undergoing radiation therapy for medulloblastoma.

PURPOSE: Advantages to computerized cognitive assessment include increased precision of response time measurement and greater availability of alternate forms. Cogstate is a computerized cognitive battery developed to monitor attention, memory, and processing speed. Although the literature suggests the domains assessed by Cogstate are areas of deficit in children undergoing treatment for medulloblastoma, the validity of Cogstate in this population has not been previously investigated. METHODS: Children participating in an ongoing prospective trial of risk-adapted therapy for newly diagnosed medulloblastoma (n = 73; mean age at baseline = 12.1 years) were administered Cogstate at baseline (after surgery, prior to adjuvant therapy) and 3 months later (6 weeks after completion of radiation therapy). Gold-standard neuropsychological measures of similar functions were administered at baseline. RESULTS: Linear mixed models revealed performance within age expectations at baseline across Cogstate tasks. Following radiation therapy, there was a decline in performance on Cogstate measures of reaction time (Identification and One Back). Females exhibited slower reaction time on One Back and Detection tasks at baseline. Higher-dose radiation therapy and younger age were associated with greater declines in performance. Pearson correlations revealed small-to-moderate correlations between Cogstate reaction time and working memory tasks with well-validated neuropsychological measures. CONCLUSIONS: Cogstate is sensitive to acute cognitive effects experienced by some children with medulloblastoma and demonstrates associations with clinical predictors established in the literature. Correlations with neuropsychological measures of similar constructs offer additional evidence of validity. The findings provide support for the utility of Cogstate in monitoring acute cognitive effects in pediatric cancer.

Do Wellness Tourists Get Well? An Observational Study of Multiple Dimensions of Health and Well-Being After a Week-Long Retreat.

BACKGROUND: Wellness retreats use many complementary and alternative therapies within a holistic residential setting, yet few studies have evaluated the effect of retreat experiences on multiple dimensions of health and well-being, and no published studies have reported health outcomes in wellness tourists. OBJECTIVES: To assess the effect of a week-long wellness-retreat experience in wellness tourists. DESIGN: A longitudinal observational study with outcomes assessed upon arrival and departure and 6 weeks after the retreat. SETTING: A rural health retreat in Queensland, Australia. INTERVENTIONS: A holistic, 1-week, residential, retreat experience that included many educational, therapeutic, and leisure activities and an organic, mostly plant-based diet. OUTCOME MEASURES: Multiple outcome measures were performed upon arrival and departure and 6 weeks after the retreat. These included anthropometric measures, urinary pesticide metabolites, a food and health symptom questionnaire, the Five Factor Wellness Inventory, the General Self Efficacy questionnaire, the Pittsburgh Insomnia Rating Scale, the Depression Anxiety Stress Scale, the Profile of Mood States, and the Cogstate cognitive function test battery. RESULTS: Statistically significant improvements (p < 0.05) were seen in almost all measures (n = 37) after 1 week and were sustained at 6 weeks (n = 17). There were statistically significant improvements (p < 0.001) in all anthropometric measures after 1 week, with reductions in abdominal girth (2.7 cm), weight (1.6 kg), and average systolic and diastolic pressure (-16.1 mmHg and -9.3 mmHg, respectively). Statistically significant improvements (p < 0.05) were also seen in psychological and health symptom measures. Urinary pesticide metabolites were detected in pooled urine samples before the retreat and were undetectable after the retreat. CONCLUSION: Retreat experiences can lead to substantial improvements in multiple dimensions of health and well-being that are maintained for 6 weeks. Further research that includes objective biomarkers and economic measures in different populations is required to determine the mechanisms of these effects and assess the value and relevance of retreat experiences to clinicians and health insurers.