Adrian Schembri

Clinical utility of the cogstate brief battery in identifying cognitive impairment in mild cognitive impairment and Alzheimer’s disease

BackgroundPrevious studies have demonstrated the utility and sensitivity of the CogState Brief Battery (CBB) in detecting cognitive impairment in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) and in assessing cognitive changes in the preclinical stages of AD. Thus, the CBB may be a useful screening tool to assist in the management of cognitive function in clinical settings. In this study, we aimed to determine the utility of the CBB in identifying the nature and magnitude of cognitive impairments in MCI and AD.MethodsHealthy adults (n = 653) adults with amnestic MCI (n = 107), and adults with AD (n = 44) who completed the CBB participated in this study. Composite Psychomotor/Attention and Learning/Working Memory scores were computed from the individual CBB tests. Differences in composite scores were then examined between the three groups; and sensitivity and specificity analyses were conducted to determine cut scores for the composite scores that were optimal in identifying MCI- and AD-related cognitive impairment.ResultsLarge magnitude impairments in MCI (g = 2.2) and AD (g = 3.3) were identified for the learning/working memory composite, and smaller impairments were observed for the attention/psychomotor composite (g’s = 0.5 and 1, respectively). The cut-score associated with optimal sensitivity and specificity in identifying MCI-related cognitive impairment on the learning/working memory composite was -1SD, and in the AD group, this optimal value was -1.7SD. Both composite scores showed high test-retest reliability (r = 0.95) over four months. Poorer performance on the memory composite was also associated with worse performance on the Mini Mental State Exam and increasing severity on the Clinical Dementia Rating Scale sum of boxes score.ConclusionsResults of this study suggest that the CogState learning/working memory composite score is reduced significantly in CI and AD, correlate well with measures of disease classification and are useful in identifying memory impairment related to MCI- and AD.

Detecting Cognitive Impairment After Concussion: Sensitivity of Change From Baseline and Normative Data Methods Using the CogSport/Axon Cognitive Test Battery

Concussion-related cognitive impairments are typically evaluated with repeated neuropsychological assessments where post-injury performances are compared with pre-injury baseline data (baseline method). Many cases of concussions, however, are evaluated in the absence of baseline data by comparing post-injury performances with normative data (normative method). This study aimed to compare the sensitivity and specificity of these two methods using the CogSport/Axon test battery. Normative data and reliable change indices were computed from a non-injured athlete sample (n = 235). Test-retest data from non-injured (n = 260) and recently concussed (n = 29) athlete samples were then used to compare the two methods. The baseline method was found to be more sensitive than the normative method, and both methods had high specificity and overall correct classification rates. This suggests that while the normative method identifies most cases of recent concussions, the baseline method remains a more precise approach to assessing concussion-related cognitive impairments.

Minimal Cognitive Impairment in UK HIV Positive Men Who Have Sex with Men: Effect of Case Definitions, and Comparison with the General Population and HIV Negative Men.

Background:To determine the prevalence of neurocognitive impairment (NCI) in UK HIV-positive and HIV-negative men who have sex with men (MSM). Methods:HIV-positive and HIV-negative participants were recruited to a cross-sectional study from 2 London clinics and completed computer-assisted neuropsychological tests and questionnaires of depression, anxiety, and activities of daily living. Published definitions of HIV-associated neurocognitive disorders (HAND) and global deficit scores were used. Age- and education-adjusted neuropsychological test scores were directly compared with reference population data. Results:A total of 248 HIV-positive and 45 HIV-negative MSM participated. In the HIV-positive group, median time since diagnosis was 9.4 years, median CD4+ count was 550 cells per cubic millimeter, and 88% were on antiretroviral therapy. Prevalence of HAND was 21.0% in HIV-positive MSM (13.7% asymptomatic neurocognitive impairment, 6.5% mild neurocognitive disorder, and 0.8% HIV-associated dementia). Using a global deficit score threshold of 0.5, the prevalence of NCI was 31.5% (when averaged over 5 neuropsychological domains) and 40.3% (over 10 neuropsychological test scores). These results were not significantly different from the HIV-negative study sample. No consistent pattern of impairment was seen in HIV-positive patients relative to general male population data (n = 380). Conclusions:We found a prevalence of HAND and degree of impairment on neuropsychological testing of HIV-positive MSM that could represent a normal population distribution. These findings suggest that NCI may be overestimated in HIV-positive MSM, and that the attribution of NCI to HIV infection implied by the term HAND requires revision.

Exercise, Sedentary Pastimes, and Cognitive Performance in Healthy Older Adults

Background: Moderately vigorous physical activity (MVPA) provides a protective affect against cognitive decline and cardiovascular risk factors. Less is known about sedentary pastimes or non exercise physical activity (NEPA) and cognitive performance. Method: 125 healthy adults 65 or older with no clinical evidence of cognitive impairment were enrolled. The CogState computerized neurocognitive battery was administered. Leisure activities were measured using the Community Health Activity Program for Seniors (CHAMPS). Results: Sedentary pastimes were associated with executive dysfunction (P = 0.01); MVPA with high memory scores (P = 0.05) and NEPA with improved working memory (P = 0.05). Only sedentary pastimes and executive dysfunction retained significance after correction for multiple comparisons. Smoking and alcohol confounded the association of memory with sedentary pastimes and MVPA. Conclusions: Study highlights: negative impact of sedentary pastimes on executive function, need for additional investigation of sedentary behavior, NEPA, the impact of addictions upon activity in late life.

The nature and rate of cognitive maturation from late childhood to adulthood

To better understand the nature and rate of cognitive change across adolescence, the Cogstate Brief Battery (CBB) was utilized to assess psychomotor function, attention, working memory, and visual learning in individuals aged 10–18 years old. Since all CBB tasks have equivalent perceptual, motor, and linguistic demands as well as being appropriate for both children and adults, this approach allowed direct across-age comparison of multiple cognitive domains. Exponential decreases in reaction time and linear increases in accuracy were observed across adolescent development in a cross-sectional sample of 38,778 individuals and confirmed in a 5788 individual longitudinal sample with 1-year repeat assessments. These results have important implications for the repeated assessment of cognition during development where expected maturational changes in cognition must be accounted for during cognitive testing.

Simultaneous treatment of neurocognitive and psychiatric symptoms in veterans with post-traumatic stress disorder and history of mild traumatic brain injury: a pilot study of mindfulness-based stress reduction

Treating patient populations with significant psychiatric and neurocognitive symptomatology can present a unique clinical dilemma: progress in psychotherapy can be significantly fettered by cognitive deficits, whereas neurocognitive rehabilitation efforts can be ineffective because of psychiatric overlay. Application of mindfulness-based interventions to address either cognitive or psychiatric symptoms in isolation appears efficacious in many contexts; however, it remains unclear whether this type of intervention might help address simultaneous neurocognitive and psychiatric symptomatology. In a pre-post mixed methods design pilot study, nine Veterans with post-traumatic stress disorder (PTSD) and a history of mild traumatic brain injury with chronic cognitive complaints participated in Mindfulness-Based Stress Reduction (MBSR). Clinical interview, questionnaires, and attention and PTSD measures were administered immediately before, immediately after, and 3 months after MBSR completion. Qualitative and quantitative findings suggest high levels of safety, feasibility, and acceptability. Measurement of attention revealed significant improvement immediately following MBSR (p < 0.05, d = 0.57) and largely sustained improvement 3 months after completion of MBSR (p < 0.10, d = 0.48). Significant reduction in PTSD symptoms was found immediately after MBSR (p < 0.05, d = -1.56), and was sustained 3 months following MBSR completion (p < 0.05, d = -0.93). These results warrant a randomized controlled trial follow-up. Potential mechanisms for the broad effects observed will be explored.

Amyloid burden and incident depressive symptoms in preclinical Alzheimer’s disease

BACKGROUND Relationships between depression and Alzheimers disease (AD) may become clearer if studied in preclinical AD where dementia is not present. METHOD The aim of this study was to evaluate prospectively, relationships between brain amyloid-β (Aβ), depressive symptoms and screen positive depression in cognitively normal (CN) older adults. Depressive symptoms were measured with the Geriatric Depression Inventory (GDS-15) in CN adults from the Australian Imaging Biomarkers and Lifestyle (AIBL) study without depression at baseline and classified as having abnormally high (Aβ+; n = 136) or low (Aβ-; n = 449) Aβ according to positron emission tomography at 18-month intervals over 72 months. RESULTS Incident cases of screen positive depression were not increased in Aβ+ CN adults although small increases in overall depressive symptoms severity (d = - 0.25; 95% CI, - 0.45, - 0.05) and apathy-anxiety symptoms (d = - 0.28; 95% CI - 0.48, - 0.08) were. LIMITATIONS As the AIBL sample is an experimental sample, no individuals had severe medical illnesses or significant psychiatric disorders. Additionally, individuals who had evidence of screen-positive depression at screening were excluded from enrolment in the AIBL study. Thus, the current data can be considered only as providing a foundation for understanding relationships between Aβ and depression in preclinical AD. CONCLUSIONS These results suggest that the presence of a depressive disorder or even increased depressive symptoms are themselves unlikely to be a direct consequence of increasing Aβ. New depressive disorders presenting in CN older adults could therefore be investigated for aetiologies beyond AD.

Correlation between the Cogstate computerized measure and WAIS-IV among birth cohort mothers

Objective Large studies, with limited resources call for cost-effective cognitive assessment methods. Computerized tests offer viable alternatives but more data are needed on their functioning. Our aim was to evaluate the overlap between a computerized neuropsychological test battery and a traditional test of general intelligence (IQ). Method Cognitive functioning was assessed in birth cohort mothers (n = 80) with two widely used methods: Cogstate, computerized test battery, and WAIS-IV, a traditional IQ test. Correlational analyses were conducted. Results We found weak-to-moderate correlations between the measures, except for verbal comprehension. The indices of overall performance showed more consistent correlations than Subtests. Discussion The overall correlations were in accordance with earlier studies. Cogstate is relatively independent of verbal comprehension abilities. The choice of the cognitive assessment method should be strongly guided by the research question. More studies are needed to evaluate the applicability of the Cogstate Composite Score in cognitive screening.

Prolonged-Release Fampridine as Adjunct Therapy to Active Motor Training in MS Patients: A Pilot, Double-Blind, Randomized, Placebo-Controlled Study:

Background Both prolonged-release fampridine (PRF) and enabling active motor training (EAMT) are beneficial in multiple sclerosis (MS) patients. Their combined effect is, however, understudied. Objective The objective of this paper is to determine if PRF augments the beneficial effect of EAMT in MS patients as opposed to placebo. Method This is a pilot, randomized, placebo-controlled, double-blind 14-week study. Participants were randomly assigned to receive PRF 10 mg BID (n = 21) or placebo (n = 20). All patients underwent EAMT during the first six weeks. Patients were assessed at –4, 0, 6 and 14 weeks. Results Both groups remained stable between –4 to 0 weeks and showed statistically significant improvements for the six-minute walk and the five-times-sit-to-stand test at weeks 6 and 14. The PRF-treated group achieved a greater mean percentage improvement and a higher incidence of responders in all three tasks at both time points. The study was, however, underpowered to reach statistical significance. Conclusion Our results confirm previous studies demonstrating that MS patients, despite significant disability, do benefit from a rehabilitation program. Our study is the first to show a trend suggesting that PRF in MS patients appears to enhance the benefit of EAMT. Further studies are required to confirm this. Clinical trial registration number with Clinicaltrial.gov: NCT02146534

A pilot evaluation of a computer-based psychometric test battery designed to detect impairment in patients with cirrhosis

Background Psychometric testing is used to identify patients with cirrhosis who have developed hepatic encephalopathy (HE). Most batteries consist of a series of paper-and-pencil tests, which are cumbersome for most clinicians. A modern, easy-to-use, computer-based battery would be a helpful clinical tool, given that in its minimal form, HE has an impact on both patients’ quality of life and the ability to drive and operate machinery (with societal consequences). Aim We compared the Cogstate™ computer battery testing with the Psychometric Hepatic Encephalopathy Score (PHES) tests, with a view to simplify the diagnosis. Methods This was a prospective study of 27 patients with histologically proven cirrhosis. An analysis of psychometric testing was performed using accuracy of task performance and speed of completion as primary variables to create a correlation matrix. A stepwise linear regression analysis was performed with backward elimination, using analysis of variance. Results Strong correlations were found between the international shopping list, international shopping list delayed recall of Cogstate and the PHES digit symbol test. The Shopping List Tasks were the only tasks that consistently had P values of <0.05 in the linear regression analysis. Conclusion Subtests of the Cogstate battery correlated very strongly with the digit symbol component of PHES in discriminating severity of HE. These findings would indicate that components of the current PHES battery with the international shopping list tasks of Cogstate would be discriminant and have the potential to be used easily in clinical practice.