[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; · 5.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS).
[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. Methods: 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. Results: 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. Conclusions: 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; · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obstructive sleep apnea is a common sleep disorder in stroke patients. Obstructive sleep apnea is associated with stroke severity and poor functional outcome. Continuous positive airway pressure seems to improve functional recovery in stroke rehabilitation. To date, the effect of continuous positive airway pressure on cognitive functioning in stroke patients is not well established. The current study will investigate the effectiveness of continuous positive airway pressure on both cognitive and functional outcomes in stroke patients with obstructive sleep apnea.Methods/design: A randomized controlled trial will be conducted on the neurorehabilitation unit of Heliomare, a rehabilitation center in the Netherlands. Seventy stroke patients with obstructive sleep apnea will be randomly allocated to an intervention or control group (n = 2x35). The intervention will consist of four weeks of continuous positive airway pressure treatment. Patients allocated to the control group will receive four weeks of treatment as usual. Outcomes will be assessed at baseline, immediately after the intervention and at two-month follow-up.In a supplementary study, these 70 patients with obstructive sleep apnea will be compared to 70 stroke patients without obstructive sleep apnea with respect to cognitive and functional status at rehabilitation admission. Additionally, the societal participation of both groups will be assessed at six months and one year after inclusion.
This study will provide novel information on the effects of obstructive sleep apnea and its treatment with continuous positive airway pressure on rehabilitation outcomes after stroke.Trial registration: Trial registration number: Dutch Trial Register NTR3412.
[Show abstract][Hide abstract] ABSTRACT: Scales of global cognition and behavior, often used as endpoints for intervention trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI), are insufficiently responsive (i.e., relatively insensitive to change). Large patient samples are needed to detect beneficial drug effects. Therefore, magnetic resonance imaging (MRI) measures of cerebral atrophy have been proposed as surrogate endpoints.
To examine how neuropsychological assessment compares to MRI in this respect.
We measured hippocampal atrophy, cortical thickness, and performance on neuropsychological tests in memory clinic patients at baseline and after two years. Neurologists rated the patients as cognitively normal (n = 28; Clinical Dementia Rating, CDR = 0) or as impaired (n = 34; CDR > 0). We administered five tests of memory, executive functioning, and verbal fluency. A composite neuropsychological score was calculated by taking the mean of the demographically corrected standard scores. MRI was done on a 3 Tesla scanner. Volumetric measurements of the hippocampus and surrounding cortex were made automatically using FreeSurfer software.
The composite neuropsychological score deteriorated 0.6 SD in the impaired group, and was virtually unchanged in the normal group. Annual hippocampal atrophy rates were 3.4% and 0.6% in the impaired and normal cognition groups, respectively. Estimates of required sample sizes to detect a 50% reduction in rate of change were larger using rate of hippocampal atrophy (n = 131) or cortical thickness (n = 488) as outcome compared to change scores on neuropsychological assessment (n = 62).
Neuropsychological assessment is more responsive than MRI measures of brain atrophy for detecting disease progression in memory clinic patients with MCI or AD.
Journal of Alzheimer's disease: JAD 01/2014; · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dementia in Parkinson's disease (PD) is a serious health issue and a major concern for many patients. In most cases mild cognitive impairment (MCI) is considered a transitional stage between normal cognitive functioning and dementia which is of potential importance in the early identification of patients at risk for dementia. Recently, the Movement Disorder Society (MDS) proposed diagnostic criteria for MCI in PD (PD-MCI). These criteria comprise two operationalizations: Level I (based on an abbreviated assessment) and Level II (based on comprehensive neuropsychological evaluation permitting MCI subtyping). These criteria need to be validated. This paper describes a project aiming to validate the MDS PD-MCI criteria by pooling and analyzing cross-sectional and longitudinal neuropsychological databases comprising ≥5,500 PD patients and ≥1,700 controls. After applying the MDS PD-MCI Level I and Level II criteria, rates of conversion to PD-dementia and predictive variables for conversion to PD-dementia will be established. This study will also assist in identifying whether revisions of the PD-MCI criteria are required.
[Show abstract][Hide abstract] ABSTRACT: In the past, the practice of symptom validity assessment (SVA) in European countries was considerably lagging behind developments in North America, with the topic of malingering being largely taboo for psychological and medical professionals. This was being changed in the course of the past decade with a growing interest in methods for the assessment of negative response bias. European estimates of suboptimal test performance in civil and social forensic contexts point at base rates similar to those obtained in North America. Symptom over-reporting and underperformance in neuropsychological examinations appear to occur in a sizable proportion of patients. Although there is considerable progress in establishing SVA as an integral and indispensable part of psychological and neuropsychological assessment in some countries, others appear to lag behind. In some countries there is still enormous resistance against SVA from part of the neuropsychological and psychiatric communities.
[Show abstract][Hide abstract] ABSTRACT: We examined the development of Parkinson disease (PD)-mild cognitive impairment (MCI) in patients with newly diagnosed PD over 5 years using recently proposed consensus criteria, and we assessed the reliability of the criteria.
Patients with PD (n = 123) underwent extensive neuropsychological testing at baseline and after 3 (n = 93) and 5 years (n = 59). Two neuropsychologists independently applied the PD-MCI criteria to examine the interrater and intrarater reliability.
At baseline, 35% of patients had PD-MCI. Three years later, 53% of the patients had PD-MCI. At 5-year follow-up, 20 patients who had PD-MCI at an earlier assessment had converted to PD dementia and 50% of the remaining patients without dementia had MCI. The interrater reliability (kappa) was 0.91. The intrarater reliabilities were 0.85 and 0.96.
Approximately one-third of patients with newly diagnosed PD fulfill the consensus criteria for PD-MCI; after 5 years, this proportion is approximately 50% of patients without dementia. The criteria have good interrater and intrarater reliability.
[Show abstract][Hide abstract] ABSTRACT: Objectives: To assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. Participants: Patients with mild cognitive impairment (MCI; n=181) were included. Mean follow-up was 38.9 months (range 5.5–75.9). Main outcome measures: Diagnostic accuracy of individual instruments and incremental value of entorhinal cortex volume on MRI and p-τ/Aβ ration in CSF after administration of Rey's Auditory Verbal Learning Memory Test are calculated and expressed as the 'Net Reclassification Improvement' (NRI), which is the change in the percentage of individuals that are correctly diagnosed as Alzheimer or non-Alzheimer case. Results: Tested in isolation, a short memory test, MRI and CSF all substantially contribute to the differentiation of those MCI patients who remain stable during follow-up from those who progress to develop Alzheimer's disease. The memory test, MRI and CSF improved the diagnostic classification by 21% (95% CI 15.1 to 26.9), 22.1% (95% CI 16.1 to 28.1) and 18.8% (95% CI 13.1 to 24.5), respectively. After administration of a short memory test, however, the NRI of MRI is +1.1% (95% CI 0.1 to 3.9) and of CSF is −2.2% (95% CI −5.6 to −0.6). Conclusions: After administration of a brief test of memory, MRI or CSF do not substantially affect diagnostic accuracy for predicting progression to Alzheimer's disease in patients with MCI. The NRI is an intuitive and easy to interpret measure for evaluation of potential added value of new diagnostic instruments in daily clinical practice.
[Show abstract][Hide abstract] ABSTRACT: The "dementia profile" is used to reduce false positives on the Word Memory Test (WMT). Provided that this profile reflects genuine memory impairment, corresponding cognitive deficits should be found in neuropsychological testing. We examined whether a WMT dementia profile is a significant indicator of cognitive impairment and/or decline. In addition, we evaluated the classification accuracy for the clinical diagnosis of dementia. Elderly patients (n = 167) with cognitive complaints were given an extensive neuropsychological test battery, including the WMT. This was repeated 2 years later. The results demonstrate that patients with the dementia profile have a higher chance of showing real cognitive impairment at baseline, and even more so 2 years later. They showed a faster cognitive decline than patients who passed the WMT effort subtasks. Sensitivity of the profile was a moderate 60%. However, the positive predictive value was high, viz. 81% at baseline and 93% at follow-up.
Archives of Clinical Neuropsychology 05/2013; · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cognitive change is frequently observed in patients with Parkinson's disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here. (JINS, 2013, 19, 1-14).
Journal of the International Neuropsychological Society 04/2013; · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Psychogenic movement disorders are disorders of movements that cannot be explained by a known neurological disorder and are assumed to be associated with psychiatric symptoms such as depression and anxiety. OBJECTIVE: To examine the neuropsychological profile of patients with psychogenic movement disorders. METHODS: We examined cognitive functioning using neuropsychological tests in 26 patients with clinically established psychogenic jerky movement disorders (PMD). We included 16 patients with Gilles de la Tourette syndrome (GTS) who served as a patient control group, in addition to 22 healthy control subjects. Non-credible test performance was detected using a Symptom Validity Test (SVT). Psychopathology was also assessed. RESULTS: Apart from a worse performance on a verbal memory task, no evidence of neuropsychological impairments was found in our PMD sample. Interestingly however, patients with PMD reported more cognitive complaints in daily life and performed worse on the SVT than the two other groups. Patients with GTS did not report, or show, cognitive impairments. In patients with PMD, we found associations between verbal learning, SVT performance and severity of depression and anxiety complaints. CONCLUSIONS: We conclude that some patients with PMD show non-credible cognitive symptoms. In contrast, no evident cognitive impairments were present in patients with PMD or GTS. Our study underlines the importance of assessment of non-credible response in patients with PMD. Additionally, non-credible response might aid in the differentiation of PMD from other movement disorders.
Journal of neurology, neurosurgery, and psychiatry 02/2013; · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preclinical studies suggest that dexamphetamine (dAMPH) can lead to monoaminergic neurotoxicity. This exploratory study aimed to investigate effects of recreational dAMPH use on the dopamine (DA) and noradrenaline (NA) systems in humans. To that purpose, eight male abstinent dAMPH (26.0±4.0 years) users and 10 age- and IQ-matched male healthy control subjects (23.0±3.8) underwent neuropsychological testing sensitive to DAergic function and single photon emission computed tomography (SPECT) scanning with [(123)I]FP-CIT to determine striatal DA transporter (DAT) binding. In addition, changes in cerebral blood flow (CBF) induced by the DA/NA reuptake inhibitor methylphenidate (MPH) were measured using pharmacological magnetic resonance imaging (phMRI). Performance of dAMPH users was significantly worse on executive function and verbal memory tasks. Striatal DAT binding ratios were on average lower in dAMPH users (near-significant, p=0.05). In addition, CBF in control subjects decreased significantly in response to MPH in gray matter and basal ganglia, among which the striatum, thalamus and hippocampus by 10% to 29%. However, in dAMPH users the CBF response was blunted in most brain areas studied, only decreasing in the hippocampus and orbitofrontal cortex. When comparing groups, CBF response was found to be significantly different in the thalamus with a decrease for healthy controls and a blunted response in dAMPH users. Collectively, our findings of a blunted hemodynamic response in monoaminergic regions, in combination with indications for lower striatal DAT binding and poorer behavioral measures are likely to represent DAergic dysfunction in dAMPH users, although NAergic dysfunction may also play a role.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 02/2013; · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: In Parkinson disease (PD), the rate of clinical progression is highly variable. To date, there are conflicting findings concerning the prognostic factors influencing the rate of progression. Methodologic issues such as the use of selected patients from therapeutic trials, and short durations of follow-up probably underlie this problem. We therefore designed a prospective follow-up study of a cohort of newly diagnosed patients with PD. METHODS: A cohort of 129 patients with newly diagnosed PD was assessed at baseline, and 1, 2, 3, and 5 years later. The rate of progression and its prognostic factors on the level of motor impairments, disability, and quality of life were investigated using linear mixed-model analysis. RESULTS: Annual increase of motor impairments measured with the Unified Parkinson's Disease Rating Scale-Motor Examination was estimated to be 2.46 points (95% confidence interval: 2.05-2.88). The main determinants of faster increase of motor impairments were male sex and cognitive dysfunction at the time of diagnosis. The main determinants of faster increase of disability were higher age at onset, cognitive dysfunction, and the presence of levodopa-nonresponsive motor symptoms at the time of diagnosis. No clinically relevant determinants were found for the decrease in quality of life. CONCLUSION: This study shows the importance of nondopaminergic symptoms at the time of diagnosis, because these symptoms are the main determinants of increased disability in the first 5 years of the disease.
[Show abstract][Hide abstract] ABSTRACT: Patients with mild cognitive impairment (MCI) do not always convert to dementia. In such cases, abnormal neuropsychological test results may not validly reflect cognitive symptoms due to brain disease, and the usual brain-behavior relationships may be absent. This study examined symptom validity in a memory clinic sample and its effect on the associations between hippocampal volume and memory performance. Eleven of 170 consecutive patients (6.5%; 13% of patients younger than 65 years) referred to memory clinics showed noncredible performance on symptom validity tests (SVTs, viz. Word Memory Test and Test of Memory Malingering). They were compared to a demographically matched group (n = 57) selected from the remaining patients. Hippocampal volume, measured by an automated volumetric method (Freesurfer), was correlated with scores on six verbal memory tests. The median correlation was r = .49 in the matched group. However, the relation was absent (median r = -.11) in patients who failed SVTs. Memory clinic samples may include patients who show noncredible performance, which invalidates their MCI diagnosis. This underscores the importance of applying SVTs in evaluating patients with cognitive complaints that may signify a predementia stage, especially when these patients are relatively young.
Journal of Clinical and Experimental Neuropsychology 12/2012; · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 ; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION: Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.
The Lancet Neurology 11/2012; · 23.92 Impact Factor