[Show abstract][Hide abstract] ABSTRACT: Stroke survivors frequently suffer from executive impairments even in the chronic phase after stroke, and there is a need for improved rehabilitation of these functions. One way of improving current rehabilitation treatment may be by online cognitive training. Based on a review of the effectiveness of computer-based cognitive training in healthy elderly, we concluded that cognitive flexibility may be a key element for an effective training, which results in improvements not merely on trained tasks but also in untrained tasks (i.e., far transfer). The aim of the current study was to track the behavioral and neural effects of computer-based cognitive flexibility training after stroke. We expected that executive functioning would improve after the cognitive flexibility training, and that neural activity and connectivity would normalize towards what is seen in healthy elderly.
The design was a multicenter, double blind, randomized controlled trial (RCT) with three groups: an experimental intervention group, an active control group who did a mock training, and a waiting list control group. Stroke patients (3 months to 5 years post-stroke) with cognitive complaints were included. Training consisted of 58 half-hour sessions spread over 12 weeks. The primary study outcome was objective executive function. Secondary measures were improvement on training tasks, cognitive flexibility, objective cognitive functioning in other domains than the executive domain, subjective cognitive and everyday life functioning, and neural correlates assessed by both structural and resting-state functional Magnetic Resonance Imaging. The three groups were compared at baseline, after six and twelve weeks of training, and four weeks after the end of the training. Furthermore, they were compared to healthy elderly who received the same training.
The cognitive flexibility training consisted of several factors deemed important for effects that go beyond improvement on merely the training task themselves. Due to the presence of two control groups, the effects of the training could be compared with spontaneous recovery and with the effects of a mock training. This study provides insight into the potential of online cognitive flexibility training after stroke. We also compared its results with the effectiveness of the same training in healthy elderly.
The Netherlands National Trial Register NTR5174 . Registered 22 May 2015.
[Show abstract][Hide abstract] ABSTRACT: Cognitive impairment is present in approximately 30% of patients with amyotrophic lateral sclerosis (ALS) and, especially when severe, has a negative impact on survival and caregiver burden. Our 2010 meta-analysis of the cognitive profile of ALS showed impairment of fluency, executive function, language and memory. However, the limited number of studies resulted in large confidence intervals. To obtain a more valid assessment, we updated the meta-analysis and included methodological improvements (controlled data extraction, risk of bias analysis and effect size calculation of individual neuropsychological tests). Embase, Medline and PsycInfo were searched for neuropsychological studies of non-demented patients with ALS and age-matched and education-matched healthy controls. Neuropsychological tests were categorised in 13 cognitive domains and effect sizes (Hedges' g) were calculated for each domain and for individual tests administered in ≥5 studies. Subgroup analyses were performed to assess the influence of clinical and demographic variables. Forty-four studies were included comprising 1287 patients and 1130 healthy controls. All cognitive domains, except visuoperceptive functions, showed significant effect sizes compared to controls. Cognitive domains without bias due to motor impairment showed medium effect sizes (95% CI): fluency (0.56 (0.43 to 0.70)), language (0.56 (0.40 to 0.72)), social cognition (0.55 (0.34 to 0.76)), or small effect sizes: delayed verbal memory 0.47 (0.27 to 0.68)) and executive functions (0.41 (0.27 to 0.55)). Individual neuropsychological tests showed diverging effect sizes, which could be explained by bias due to motor impairment. Subgroup analyses showed no influence of bulbar disease onset and depression and anxiety on the cognitive outcomes. The cognitive profile of ALS consists of deficits in fluency, language, social cognition, executive functions and verbal memory. Social cognition is a new cognitive domain with a relatively large effect size, highlighting the overlap between ALS and frontotemporal dementia. The diverging effect sizes for individual neuropsychological tests show the importance of correction for motor impairment in patients with ALS. These findings have implications for bedside testing, the design of cognitive screening measures and full neuropsychological examinations.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Journal of neurology, neurosurgery, and psychiatry 08/2015; DOI:10.1136/jnnp-2015-310734 · 6.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to assess whether multivariate normative comparison (MNC) improves detection of HIV-1 associated neurocognitive disorder (HAND) as compared with Frascati and Gisslén criteria.
:One-hundred and three HIV-1 infected men with suppressed viremia on combination antiretroviral therapy (cART) for at least 12 months and 74 HIV-uninfected male controls (comparable regarding age, ethnicity, sexual orientation, premorbid intelligence and educational level), aged at least 45 years, underwent neuropsychological assessment covering six cognitive domains (fluency, attention, information processing speed, executive function, memory and motor function). Frascati and Gisslén criteria were applied to detect HAND. Next, MNC was performed to compare the cognitive scores of each HIV-positive individual against the cognitive scores of the control group.
HIV-infected men showed significantly worse performance on the cognitive domains of attention, information processing speed and executive function compared with HIV-uninfected controls. HAND by Frascati criteria was highly prevalent in HIV-infected [48%; 95% confidence interval (95% CI) 38-58] but nearly equally so in HIV-uninfected men (36%; 95% CI 26-48), confirming the low specificity of this method. Applying Gisslén criteria, HAND-prevalence was reduced to 5% (95% CI 1-9) in HIV-infected men and to 1% (95% CI 1-3) among HIV-uninfected controls, indicating better specificity but reduced sensitivity. MNC identified cognitive impairment in 17% (95% CI 10-24) of HIV-infected men and in 5% (95% CI 0-10) of the control group (P = 0.02, one-tailed), showing an optimal balance between sensitivity and specificity.
Prevalence of cognitive impairment in HIV-1 infected men with suppressed viremia on cART estimated by MNC was much higher than that estimated by Gisslén criteria, although the false positive rate was greatly reduced compared with the Frascati criteria. VIDEO ABSTRACT::
AIDS (London, England) 01/2015; 29(5). DOI:10.1097/QAD.0000000000000573 · 5.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Despite the declined incidence of severe neurological complications such as HIV‐encephalopathy, HIV‐infection in children is still associated with a range of cognitive problems. Studies comparing HIV‐infected children to socioeconomically (SES)‐matched controls are lacking, while most HIV‐infected children in industrialized countries are immigrants with a relatively low SES.
Methods: This cross‐sectional study included perinatally HIV‐infected children and controls matched for age, gender, ethnicity and SES, who completed a neuropsychological assessment (NPA) evaluating intelligence, information processing speed, attention, memory, executive‐ and visual‐motor functioning. Multivariate normative comparison (MNC) was used to assess the prevalence of cognitive impairment in the HIV‐infected group. Multivariable regression analyses were performed to identify HIV‐ and cART‐related factors associated with cognitive performance.
Results: In total, 35 perinatally HIV‐infected (median age: 13.8 years, median CD4+ T‐cells: 770*106/L, 83% with an undetectable HIV VL) and 37 healthy children (median age: 12.1 years) were included. HIV‐infected children scored lower than the healthy controls on all cognitive domains (e.g. intelligence quotient (IQ): 76 [SD 15.7] and 87.5 [SD 13.6] for HIV‐infected versus healthy children; P=0.002). Cognitive impairment was found in 6 HIV‐infected children (17%). The CDC clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient ‐22.98, P=0.010).
Conclusion: Our results show that cognitive performance of HIV‐infected children is poor as compared to SES‐matched healthy controls. Gaining insight in these cognitive deficits is essential as subtle impairments may progress to more pronounced complications, that will influence future intellectual performance, job opportunities and community participation of HIV‐infected children.
[Show abstract][Hide abstract] ABSTRACT: Background
People with autism spectrum disorders (ASDs) experience executive function (EF) deficits. There is an urgent need for effective interventions, but in spite of the increasing research focus on computerized cognitive training, this has not been studied in ASD. Hence, we investigated two EF training conditions in children with ASD.Methods
In a randomized controlled trial, children with ASD (n = 121, 8–12 years, IQ > 80) were randomly assigned to an adaptive working memory (WM) training, an adaptive cognitive flexibility-training, or a non-adaptive control training (mock-training). Braingame Brian, a computerized EF-training with game-elements, was used. Outcome measures (pretraining, post-training, and 6-week-follow-up) were near-transfer to trained EFs, far-transfer to other EFs (sustained attention and inhibition), and parent's ratings of daily life EFs, social behavior, attention deficit hyperactivity disorder (ADHD)-behavior, and quality of life.ResultsAttrition-rate was 26%. Children in all conditions who completed the training improved in WM, cognitive flexibility, attention, and on parent's ratings, but not in inhibition. There were no significant differential intervention effects, although children in the WM condition showed a trend toward improvement on near-transfer WM and ADHD-behavior, and children in the cognitive flexibility condition showed a trend toward improvement on near-transfer flexibility.Conclusion
Although children in the WM condition tended to improve more in WM and ADHD-behavior, the lack of differential improvement on most outcome measures, the absence of a clear effect of the adaptive training compared to the mock-training, and the high attrition rate suggest that the training in its present form is probably not suitable for children with ASD.
Journal of Child Psychology and Psychiatry 09/2014; 56(5). DOI:10.1111/jcpp.12324 · 6.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS).
fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation.
Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS<PMA<healthy controls; pFWE=0.035; z score 4.11; cluster size=11). A more caudal region in the IFG showed lower activation in patients with PMA than controls during letter fluency performance (post hoc test; pFWE=0.026). No activation differences were observed during the category fluency task.
Prefrontal activation abnormalities are related to an important clinical measure of executive dysfunction in patients with motor neuron disease with and without upper motor neuron signs.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Executive dysfunction occurs in 30-50% of amyotrophic lateral sclerosis (ALS) patients and is most frequently assessed with the verbal fluency test. The verbal fluency index (VFI) has been developed to correct for slowness of speech in ALS, and reflects the average thinking time per word. However, its use as a marker of cognitive impairment is hindered by the absence of valid norm scores. Therefore, we provide normative data for the VFI.
Dutch volunteers were demographically matched to the Dutch ALS population and completed the verbal fluency index (one-minute and three-minute spoken letter fluency). Multiple stepwise linear regression was performed to assess the influence of demographic variables, past medical history and medication use.
273 volunteers participated in this study. Educational level was negatively correlated to one-minute and three-minute VFI performance (r = -0.3 and r = -0.4, p < 0.001, respectively). No correlations for age, gender, medication and past medical history were found. A formula for standardized z-scores, corrected for educational level, for the one-minute and three-minute VFI was calculated.
We provide Dutch normative data for the spoken verbal fluency index, which can be used internationally, but validation in other languages is recommended. The findings illustrate the importance of valid disease-specific norm scores for time-dependent cognitive tests in ALS.
[Show abstract][Hide abstract] ABSTRACT: Background: There is an urgent need for effective interventions for children with autism spectrum disorders (ASDs). Current interventions focus mainly on teaching social or communicative skills, and appear to be relatively unsuccessful. Few studies focused directly on fundamental abilities such as executive functioning (EF). Children with ASD are known to experience difficulties in EF. Hence, training EFs seems promising, especially since EF interventions show positive effects in disorders highly comorbid with ASD such as ADHD.
Objectives: Two EF interventions - a working memory (WM) training, and a cognitive flexibility training - are studied in a large randomized controlled trial of children with ASD. The objective is to improve the trained EF (near transfer), and to obtain generalization of improvement to other EFs (far transfer), and to EFs in daily life (far transfer).
Methods: Children with ASD (n=102, 8-12 years, IQ>80) are randomly assigned to one of three interventions; a WM-, cognitive flexibility-, or non-EF training (active control condition) build into a computer game (Braingame Brian). The training consists of 25 sessions (40 minutes each), performed within six weeks. Each session contains both WM and cognitive flexibility training tasks. The task to be trained (e.g., WM in the WM training) increases in difficulty adaptive to performance, whereas the other task remains at a low level. To examine efficacy of the training, WM (Corsi), cognitive flexibility (switch task), and everyday EF (BRIEF) are measured pre-training, post-training, and 6-week-follow-up.
Results: Currently, data of 76 children are complete. In January 2014, data of all children will be complete. Preliminary analyses reveal that 1) Corsi performance of all children improved during the training, and remained stable at follow up. More importantly, children who received WM training improved more than children who received flexibility training, and marginally more than children who received non-EF training. 2) On the switch task all children decreased in error switch costs (difference between errors on switch and repeat trials), but increased in reaction time (RT) switch cost (difference between RT on switch and repeat trials) after the training, but overall RT decreased. Surprisingly, this improvement was manifested between post-training and follow-up. Switch task performance did not differ between the interventions. 3) All children improved on the WM, flexibility and total scale of the BRIEF, but there were no differences between the interventions. The dropout rate was 25%.
Conclusions: The WM training seems to induce near transfer; children who received WM training improved most in WM. However, the WM training does not seem to induce far transfer, i.e. both cognitive flexibility and daily life EF did not improve more than in children who received flexibility or non-EF training. The flexibility training induced neither near, nor far transfer. Children who received flexibility training did not improve more in flexibility, WM, or daily life EF compared to children who received WM or non-EF training. Since there are large individual differences within ASD, we will also apply multilevel techniques in the final analyses to find possible predictors of training outcome and compliance.
2014 International Meeting for Autism Research; 05/2014
[Show abstract][Hide abstract] ABSTRACT: The clinical significance of subjective memory complaints in the elderly participants, particularly regarding liability of subsequent progression to dementia, has been controversial. In the present study, we tested the hypothesis that severity or type of subjective memory complaints reported by patients in a clinical setting may predict future conversion to dementia.
A cohort of nondemented patients with cognitive complaints, followed up for at least 2 years or until conversion to dementia, underwent a neuropsychological evaluation and detailed assessment of memory difficulties with the Subjective Memory Complaints (SMC) Scale.
At baseline, patients who converted to dementia (36.8%) had less years of formal education and generally a worse performance in the neuropsychological assessment. There were no differences in the total SMC score between nonconverters (9.5 ± 4.2) and converters (8.9 ± 4.0, a nonsignificant difference), but nonconverters scored higher in several items of the scale.
For patients with cognitive complaints observed in a memory clinic setting, the severity of subjective memory complaints is not useful to predict future conversion to dementia.
Journal of Geriatric Psychiatry and Neurology 04/2014; 27(4). DOI:10.1177/0891988714532018 · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inleiding Een belangrijk deel van de patiënten met sikkelcelziekte heeft cognitieve problemen, zoals problemen met intellectueel en executief functioneren en verwerkingssnelheid. Eerder onderzoek heeft zich met name gericht op patiënten in de kinderleeftijd. Er is echter nog weinig kennis over cognitief functioneren bij jongvolwassen patiënten, terwijl patiënten in deze leeftijdsgroep belangrijke beslissingen moeten nemen op het gebied van studie, werk en het sociale leven.Wanneer we meer weten over het cognitief functioneren van patiënten in de jongvolwassenheid, is het mogelijk om de benodigde zorg voor deze patiëntengroep beter af te stemmen om te voorkomen dat deze groep vastloopt in de maatschappij. Methoden Tien jongvolwassen patiënten met sikkelcelziekte (HbSS; gemiddelde leeftijd 22 jaar) die onder controle staan bij het Sikkelcelcentrum van het AMC zijn geïncludeerd. De controlegroep bestond uit 20 gezonde vrijwilligers van dezelfde leeftijd en etnische achtergrond (gemiddelde leeftijd 23 jaar). Neuropsychologisch onderzoek was gericht op het in kaart brengen van intelligentie, executief functioneren, geheugen, ruimtelijk inzicht, taal, en motorische en verwerkingssnelheid. Resultaten Patiënten behaalden significant lagere scores dan gezonde controles op intellectueel en executief functioneren. Op patiëntniveau zijn er grote individuele verschillen op de resultaten van het neuropsychologisch onderzoek gevonden. Conclusie Cognitieve problemen bij patiënten met sikkelcelziekte zijn ook aanwezig in de jongvolwassenheid. De bevindingen benadrukken het belang van psycho-educatie, vroege screening van cognitief functioneren bij patiënten met sikkelcelziekte en het inzetten van korte trainingsprogramma’s.
Tijdschrift voor kindergeneeskunde 04/2014; 82(2):70-78. DOI:10.1007/s12456-014-0013-x