Harry Hallock

Cognitive training in Parkinson disease A systematic review and meta-analysis

Objective: To quantify the effects of cognitive training (CT) on cognitive and behavioral outcome measures in patients with Parkinson disease (PD). Methods: We systematically searched 5 databases for randomized controlled trials (RCTs) of CT in patients with PD reporting cognitive or behavioral outcomes. Efficacy was measured as standardized mean difference (Hedges g) of post-training change. Results: Seven studies encompassing 272 patients with Hoehn & Yahr Stages 1–3 were included. The overall effect of CT over and above control conditions was small but statistically significant (7 studies: g = 0.23, 95% confidence interval [CI] 0.014–0.44, p = 0.037). True heterogeneity across studies was low (I2 = 0%) and there was no evidence of publication bias. Larger effect sizes were noted on working memory (4 studies: g = 0.74, CI 0.32–1.17, p = 0.001), processing speed (4 studies: g = 0.31, CI 0.01–0.61, p = 0.04), and executive function (5 studies: g = 0.30, CI 0.01–0.58, p = 0.042), while effects on measures of global cognition (4 studies), memory (5 studies), visuospatial skills (4 studies), and depression (5 studies), as well as attention, quality of life, and instrumental activities of daily living (3 studies each), were not statistically significant. No adverse events were reported. Conclusions: Though still small, the current body of RCT evidence indicates that CT is safe and modestly effective on cognition in patients with mild to moderate PD. Larger RCTs are necessary to examine the utility of CT for secondary prevention of cognitive decline in this population.

Cognitive training-induced short-term functional and long-term structural plastic change is related to gains in global cognition in healthy older adults: a pilot study.

Computerized cognitive training (CCT) is a safe and inexpensive intervention to enhance cognitive performance in the elderly. However, the neural underpinning of CCT-induced effects and the timecourse by which such neural changes occur are unknown. Here, we report on results from a pilot study of healthy older adults who underwent three 1-h weekly sessions of either multidomain CCT program (n = 7) or an active control intervention (n = 5) over 12 weeks. Multimodal magnetic resonance imaging (MRI) scans and cognitive assessments were performed at baseline and after 9 and 36 h of training. Voxel-based structural analysis revealed a significant Group × Time interaction in the right post-central gyrus indicating increased gray matter density in the CCT group compared to active control at both follow-ups. Across the entire sample, there were significant positive correlations between changes in the post-central gyrus and change in global cognition after 36 h of training. A post-hoc vertex-based analysis found a significant between-group difference in rate of thickness change between baseline and post-training in the left fusiform gyrus, as well as a large cluster in the right parietal lobe covering the supramarginal and post-central gyri. Resting-state functional connectivity between the posterior cingulate and the superior frontal gyrus, and between the right hippocampus and the superior temporal gyrus significantly differed between the two groups after 9 h of training and correlated with cognitive change post-training. No significant interactions were found for any of the spectroscopy and diffusion tensor imaging data. Though preliminary, our results suggest that functional change may precede structural and cognitive change, and that about one-half of the structural change occurs within the first 9 h of training. Future studies are required to determine the role of these brain changes in the mechanisms underlying CCT-induced cognitive effects.

Cognitive Training for Post-Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Objective: To quantitatively aggregate effects of cognitive training (CT) on cognitive and functional outcome measures in patients with traumatic brain injury (TBI) more than 12-months post-injury. Design: We systematically searched six databases for non-randomized and randomized controlled trials of CT in TBI patients at least 12-months post-injury reporting cognitive and/or functional outcomes. Main Measures: Efficacy was measured as standardized mean difference (Hedges’ g) of post-training change. We investigated heterogeneity across studies using subgroup analyses and meta-regressions. Results: Fourteen studies encompassing 575 patients were included. The effect of CT on overall cognition was small and statistically significant (g = 0.22, 95%CI 0.05 to 0.38; p = 0.01), with low heterogeneity (I2 = 11.71%) and no evidence of publication bias. A moderate effect size was found for overall functional outcomes (g = 0.32, 95%CI 0.08 to 0.57, p = 0.01) with low heterogeneity (I2 = 14.27%) and possible publication bias. Statistically significant effects were also found only for executive function (g = 0.20, 95%CI 0.02 to 0.39, p = 0.03) and verbal memory (g = 0.32, 95%CI 0.14 to 0.50, p < 0.01). Conclusion: Despite limited studies in this field, this meta-analysis indicates that CT is modestly effective in improving cognitive and functional outcomes in patients with post-acute TBI and should therefore play a more significant role in TBI rehabilitation.

Posterior compensatory network in cognitively intact elders with hippocampal atrophy

Functional compensation in late life is poorly understood but may be vital to understanding long‐term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population‐based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR) or without hippocampal atrophy (PRONIL). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM‐related networks. In those with hippocampal atrophy and under conditions of basic‐SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = −0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.

CONVERGENCE AND DIVERGENCE ACROSS META-ANALYSES STUDYING COMPUTERISED COGNITIVE TRAINING IN OLDER ADULTS

about what they currently taught about dementia in their school and whether they would be interested including some form of dementia education in the future. Supplementary information was collected about the schools’ characteristics (e.g. funding stream, intake policy). Results:63 secondary schools across East Sussex, West Sussex and Brighton & Hove responded to survey. Nine schools (14.3%) reported to having some form of dementia education within their curriculum. Inclusion of dementia within the curriculum was not predicted by any school characteristics (p>0,05). Only three schools engaged with Dementia Awareness Week. The majority of schools (75.4%) expressed an interest in including some form of dementia education within their school in the future. Conclusions: Despite calls to reduce stigma and improve attitudes towards dementia, there is at present very little being taught in secondary schools. It is also concerning that many schools do not try to raise awareness or utilise freely available content. However, the fact that the majority of respondents were interested in including some form of dementia education within their school is promising.

DESIGN OF CONTROLS IN TRIALS OF COMPUTERISED COGNITIVE TRAINING IS INEFFECTUAL: A META-ANALYSIS IN HEALTHY OLDER ADULTS

Background: Rapid development and evaluation of interventions to modify ageing-related cognitive decline is key for global efforts to prevent dementia. Computerised cognitive training (CCT) is a popular and safe intervention for cognitive enrichment in older adults. CCT has been illustrated to be efficacious in improving overall cognition in a variety of populations including healthy older adults, MCI and PD. However, as effective masking of the therapeutic effect is challenging and blinding of participants is implausible, it is difficult to quantify the contribution of non-specific effects such as expectancy bias (‘placebo effect’) or the importance of trial design choices. Using a large set of randomised controlled trials (RCTs) in healthy older adults, we therefore aimed to examine the determinants of cognitive outcomes and potential moderators within the control arm of CCT trials. Methods:Medline, Embase, and PsychINFO were systematically searched for RCTs investigating the effects of CCT ( 4 hours) on performance in neuropsychological tests in older adults without neuropsychiatric disorders or diagnosed cognitive impairment. Fifty-seven trials encompassing 63 control groups and 2,712 healthy older adults were found. Results:A series of subgroup analyses revealed no statistically significant differences between: active control (k1⁄430, g1⁄40.18, 95% CI 0.12 to 0.24, I1⁄438.23) or passive control groups (k1⁄433, g1⁄40.12, 95% CI 0.08 to 0.16, I1⁄40); blinded (k1⁄432, g1⁄40.15, 95% CI 0.09 to 0.20, I1⁄432.84) or non-blinded assessors (k1⁄431, 95%, g1⁄40.16, 95% CI 0.10 to 0.21, I1⁄40); adherence to intention-to-treat analysis (k1⁄430 g1⁄40.14, 95% CI to 0.10 to 0.18, I1⁄40) or non-adherence (k1⁄433, g1⁄40.14, 95% CI 0.07 to 0.20, I1⁄437.57). We also found no difference between various design approaches or moderators of the 30 active control studies, such as: type, location or frequency of control sessions; or masking of participants. A meta-regression revealed a statistically significant relationship between the effect size in the 63 controls groups and their corresponding CCT arm (b1⁄40.22, p<0.01, R1⁄40.86). Conclusions:Contrary to common practice, supposed ‘gold standards’ of empirical science appear to be ineffectual. Given the costs associated with implementing such designs, a shift to head-to-head trials is recommended to better inform clinical and community translation.

Neuroplastic Effects of Electroconvulsive Therapy in the Prefrontal-limbic Network of Drug Resistant Depression: a Whole-brain Longitudinal SMRI Study

Background Electroconvulsive therapy (ECT) is the most effective and fast acting therapy for treatment-resistant depression (TRD). Animal research has consistently pointed to neuroplasticity as a central mechanism of ECT action (1), however evidence in humans remains scarce (2; 3). Method We assessed two independent samples of TRD patients referred for ECT. The Barcelona-sample included 13 subjects treated with bitemporal ECT and 10 healthy volunteers (HV). Four successive 3T structural MRIs were acquired: baseline, 24-48 hours after the 1st ECT session, 24-48 hours after the 9th ECT, and two weeks after ECT course completion. HV were scanned twice five weeks apart. Within the framework of the Barcelona-Sydney Clinical Imaging Collaboration, we also scanned 10 patients treated mainly with right unilateral ECT (Sydney-sample). Whole-brain longitudinal grey matter (GM) changes were measured using intra-subject diffeomorphic registration, within SPM12b. Results In the Barcelona-sample, over the course of treatment bitemporal ECT produced a linear increase of GM volume in the limbic system (involving bilateral hippocampi and amygdalae). Additionally, volumetric increase within the right subgenual cortex was detected from baseline to the 9th ECT session. Such volume changes were not observed in HV. Furthermore, GM volume expansion correlated positively with depressive symptom improvement and neurocognitive performance (memory and executive function). Hippocampal and amygdalar volume increases were replicated in the Sydney-sample, although limited to the stimulated hemisphere. Conclusions ECT effects described here could be accounted for by the induction of regionally specific structural plasticity. Nevertheless, other mechanisms such as neurovascular changes should not be discarded.