Preliminary study of working memory in children with stroke related to sickle cell disease

The verbal working memory abilities of children with stroke related to sickle cell disease (SCD) (n = 20) were compared to those of control children with SCD who had no history of stroke (n = 11). Memory span for one-, two-, and three-syllable words was assessed. For children with anterior infarcts, overall span was comparable to that of controls, but the typical effect of word length on span was reduced. For children with diffuse infarcts, overall span was reduced in comparison to that of controls, but the typical effect of word length on span was observed. For children with posterior infarcts, overall span was comparable to that of controls and the typical effect of word length on span was observed. These results provide preliminary evidence that patterns of working memory performance may vary across children with infarcts affecting different regions of the brain.     

Decreased corpus callosum size in sickle cell disease: relationship with cerebral infarcts and cognitive functioning.

We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its relationship to lesion volume, lesion location, and cognitive functioning. Twenty-eight children with SCD and 16 demographic controls completed magnetic resonance imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than for those without visible infarcts (n = 12) or control participants. Lesion volume was a robust predictor of IQ and other cognitive scores; total CC size did not typically add explanatory power for these measures. The size of the rostral body of the CC, however, independently predicted measures of distractibility, speeded production, and working memory. Posterior CC size was also decreased among many of the children with SCD, even in the absence of visible infarcts in this region. Brain morphology appears to provide additional information about SCD-related effects on the brain above and beyond visible infarcts.     

Cognitive deficits associated with frontal-lobe infarction in children with sickle cell disease

This study examined the cognitive manifestations of frontal-lobe infarction in a population of children with sickle cell disease (SCD). Forty-one patients with SCD underwent MRI. Five patients with stroke symptoms had large infarcts encroaching on the tissue of the frontal lobes. Four patients without symptoms had smaller frontal-lobe infarcts. The patients with stroke were significantly impaired on measures of intelligence, memory, and frontal-lobe function (Wisconsin Card Sorting Test, WCST) compared with both the patients with normal MRI scans ( N = 30) and a group of sibling controls ( N = 15), who did not differ from each other. Patients with covert infarction obtained scores on the intelligence tests and the WCST that fell in between those of the stroke patients and the other two groups. This trend toward impairment suggests that patients with covert infarction are at similar risk for cognitive deficits to those with stroke.     

Phonological working memory in children with phonological impairment

Phonological working memory was examined in a group of children with phonological impairment and a group of normal age-matched controls. Based on the Baddeley and Hitch model of working memory, traditional serial recall tasks of word length and phonological similarity were used to examine the efficiency of subvocal rehearsal and short-term storage, respectively. Analysis of recall performance for lists of four and six words revealed that, in comparison to agematched controls, children with phonological impairment are similarly sensitive to the effects of word length and phonological similarity, but demonstrate poorer overall recall for word lists of unrelated items. Theoretically, these findings suggest that the subvocal rehearsal mechanism and the phonological short-term store appear to be operating efficiently in this group of children with phonological impairment. Therefore their poorer recall performance may be attributable to interactions between short-term memory processes and aspects of phonological knowledge stored in long-term memory rather than to specific components of a phonological loop.     

Transcranial Doppler in adult patients with sickle cell disease

BACKGROUND: Transcranial Doppler (TCD) is the key test in determining the need for prophylactic blood transfusion to prevent stroke in children with sickle cell disease (SCD). The role of TCD in assessing stroke risk in adults with SCD as well as the pattern of TCD velocities in these patients are still undetermined. METHODS: The authors compared TCD velocities in SCD adults (n=56) with those of healthy controls (n=56). RESULTS: Velocities in SCD adults were lower than those found in children and higher than in controls and negatively correlated to hematocrit in both groups. CONCLUSION: The pattern of TCD velocities in adults with SCD is different from that described in children. Age-specific TCD criteria may assist the detection of stroke risk in these patients.     

The phonological loop in medicated patients with Parkinson''s disease: presence of phonological similarity and word length effects.

OBJECTIVE: To test the verbal subsystem of Baddeley's working memory model (the phonological loop) in patients with Parkinson's disease. METHODS: Fifteen patients with idiopathic Parkinson's disease and 15 controls were tested with a span paradigm to assess the effects reflecting the functioning of the phonological loop: the phonological similarity effect (in verbal and visual presentation), and the word length effect (in visual presentation). RESULTS AND CONCLUSIONS: The patients did not show any dysfunction of the phonological loop, reflected by the presence of phonological similarity and word length effects, but had lower spans than controls. The implications of these results for the working memory model are discussed.     

Evidence that response inhibition is a primary deficit in ADHD

The present study examined response inhibition in children with attention deficit hyperactivity disorder (ADHD; n = 58) and controls (n = 84) using three go/no-go tests -- one with high working memory demand (cognitive), one with low working memory demand (simple), and one with rewards and response costs (motivation linked) in which emphasis was on reward for responding to "go" stimuli. Results of a repeated measure analysis of variance showed a significant effect of diagnosis for errors of commission for the simple, cognitive, and motivation-linked go/no-go tests, such that children with ADHD made significantly more errors than controls. Furthermore, a significant effect of test was noted across groups, such that both children in the ADHD and control groups performed worse on the cognitive and motivation-linked tests than they did on the simple test. The diagnosis by test interaction was not significant, suggesting that ADHD participants showed a similar degree of impairment to that of controls, regardless of the degree of working memory load or feedback provided in the test. In children with ADHD, response inhibition appears to be a primary deficit that is observed even when executive function demands of tasks are minimal. Although increasing working memory demand appears to impede response inhibition, this effect is similar in ADHD and typically developing children.     

Better preservation of memory span relative to supraspan immediate recall in Alzheimer's disease

It is suggested that Alzheimer's disease (AD) patients are able to recall more items on the digit span task than on immediate free recall from a supraspan word list. Two experiments were undertaken to verify this assertion and to understand the basis of the putative span/supraspan discrepancy. The first experiment, involving 35 mildly or moderately demented AD patients, confirmed that digit span significantly exceeded immediate recall from a 10-item supraspan word list. Although digit span also exceeded supraspan recall in 38 elderly non-demented control subjects, the discrepancy was significantly greater within the AD group. In a second experiment, 19 AD cases and 20 controls were assessed with a word span task that used nouns matched by frequency and word length to nouns on the supraspan task. The magnitude of the span/supraspan discrepancy was reduced, indicating that part of the initial discrepancy was due to differences in stimulus items (digits versus common nouns). As before, AD subjects recalled more words on the span task than the supraspan task. However, in striking contrast, NC subjects recalled more words on the supraspan task, further indicating that AD patients are particularly impaired on supraspan recall. Using combined data from 106 subjects in both experiments, digit span performance correlated significantly with supraspan recall for NC but not AD subjects. Moreover, within the AD group the magnitude of the discrepancy was inversely related to a working memory measure derived from the backward digit span. The magnitude of the span/supraspan discrepancy correctly classified 88% of patients with mild dementia and 74% of controls. Results indicate that AD patients are specifically vulnerable to information overload inherent in the supraspan task, a view consistent with the perspective that AD is characterized by prominent disturbances in working memory.     

Verbal short‐term memory in Down's syndrome: An articulatory loop deficit?

Background Verbal short‐term memory, as measured by digit or word span, is generally impaired in individuals with Down's syndrome (DS) compared to mental age‐matched controls. Moving from the working memory model, the present authors investigated the hypothesis that impairment in some of the articulatory loop sub‐components is at the base of the deficient maintenance and recall of phonological representations in individuals with DS. Methods Two experiments were carried out in a group of adolescents with DS and in typically developing children matched for mental age. In the first experiment, the authors explored the reliance of these subjects on the subvocal rehearsal mechanism during a word‐span task and the effects produced by varying the frequency of occurrence of the words on the extension of the word span. In the second experiment, they investigated the functioning of the phonological store component of the articulatory loop in more detail. Results A reduced verbal span in DS was confirmed. Neither individuals with DS nor controls engaged in spontaneous subvocal rehearsal. Moreover, the data provide little support for defective functioning of the phonological store in DS. Conclusions No evidence was found suggesting that a dysfunction of the articulatory loop and lexical‐semantic competence significantly contributed to verbal span reduction in subjects with DS. Alternative explanations of defective verbal short‐term memory in DS, such as a central executive system impairment, must be considered.     

Stroke prevention and treatment in sickle cell disease

While the problem of stroke in the patients with sickle cell disease (SCD) has been known for more than 75 years, adequate preventive and treatment strategies are just now being tested. Recent data on prevalence and incidence have been obtained from the Cooperative Study of Sickle Cell Disease of more than 4000 patients with SCD observed in 23 US clinical centers over a 10-year period.1 The overall age-specific incidence of first stroke in SCD (homozygous sickle cell anemia) is low (0.13%) at ages younger than 24 months, increasing to just over 1% at ages 2 to 5 years, with only a slight decrement to 0.79% at ages 6 to 9 years. The risk of brain infarction declines until a second peak is seen at ages older than 50 years, when the incidence again increases to nearly 1.3%. Although intracranial hemorrhage does occur in young children with SCD, the risk is low compared with older children and adults. The Cooperative Study of Sickle Cell Disease reported risk factors for infarction to be prior transient ischemic attack, low steady-state hemoglobin values, and rate and recency of episodes of acute chest syndrome, as well as elevated systolic blood pressure. Risk factors for intracranial hemorrhage included low steady-state hemoglobin values and a high leukocyte count. The burden of cerebrovascular disease is even higher if subclinical magnetic resonance imaging (MRI) lesions, presumed to be ischemic, are included. The prevalence of such lesions is more than 22% in patients with SCD, and most of these patients have not reported symptoms, although specialized neuropsychological testing shows lower scores in children with silent lesions on MRI scans. Patients with a history of clinical stroke typically have infarcts in the cortex and deep white matter, whereas silent infarcts tend to be more limited to deep white matter. Common infarction patterns are characterized by wedge-shaped lesions of large-vessel territories; border zone infarctions, particularly of the middle and cerebral artery watershed region; and small punctate lesions of the deep white matter. Fat embolism to the brain and venous thromboses are encountered rarely.     

Deficits on Corsi's block-tapping task in early stage Parkinson's disease

Cognitive deficits in Parkinson's disease (PD) include disturbances in working memory. We examined sequential visuo-spatial memory span by means of an adaptation of the Corsi Block-Tapping Task in groups of medicated (n=14) and non-medicated (n=15) patients with early stage PD, and in control subjects (n=22). A deficit in memory span was found in medicated patients with early stage PD relative to controls. There were no differences between non-medicated patients relative to either controls or medicated patients. A decrease in sequential visuo-spatial memory span appears to be a relatively early feature of PD and most likely reflects executive rather than mnemonic dysfunction.     

Cerebral Vasoreactivity in Children with Sickle Cell Disease: A Transcranial Doppler Study

Background

Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with sickle cell disease (SCD) and might play a role in the pathophysiology of stroke in such patients. We examined the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared with healthy age- and gender-matched controls.

Neurobehavioral impact of sickle cell disease in early childhood.

The physical effects of sickle cell disease (SCD) begin in infancy or early childhood, yet most behavioral studies have focused on school-age children. We evaluated the impact of higher versus lower neurologic risk on language, motor abilities, executive functions, and temperament in toddlers and early preschoolers with SCD. Thirty-nine children with higher risk SCD were compared to 22 children with lower risk SCD. Language and motor abilities were lower in older compared with younger children but were unrelated to sickle cell subgroups. Executive functions, particularly working memory, were poorer in children with higher risk SCD regardless of age. Parent-reported activity level was also lower in children with higher risk. Specific behavioral influences of SCD are evident early in childhood and include working memory decrements. Executive function deficits in SCD can emerge early in life and may be an important context for other areas of cognitive and behavioral development.     

Working memory after severe traumatic brain injury.

The aim of the present study was to assess the functioning of the different subsystems of working memory after severe traumatic brain injury (TBI). A total of 30 patients with severe chronic TBI and 28 controls received a comprehensive assessment of working memory addressing the phonological loop (forward and backward digit span; word length and phonological similarity effects), the visuospatial sketchpad (forward and backward visual spans), and the central executive (tasks requiring simultaneous storage and processing of information, dual-task processing, working memory updating). Results showed that there were only marginal group differences regarding the functioning of the two slave systems, whereas patients with severe TBI performed significantly poorer than controls on most central executive tasks, particularly on those requiring a high level of controlled processing. These results suggest that severe TBI is associated with an impairment of executive aspects of working memory. The anatomic substrate of this impairment remains to be elucidated. It might be related to a defective activation of a distributed network, including the dorsolateral prefrontal cortex.     

Working memory after traumatic brain injury in children

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.     

Word-length effect in verbal short-term memory in individuals with Down's syndrome

Background Many studies have indicated that individuals with Down's syndrome (DS) show a specific deficit in short‐term memory for verbal information. The aim of the present study was to investigate the influence of the length of words on verbal short‐term memory in individuals with DS. Methods Twenty‐eight children with DS and 10 control participants matched for memory span were tested on verbal serial recall and speech rate, which are thought to involve rehearsal and output speed. Results Although a significant word‐length effect was observed in both groups for the recall of a larger number of items with a shorter spoken duration than for those with a longer spoken duration, the number of correct recalls in the group with DS was reduced compared to the control subjects. The results demonstrating poor short‐term memory in children with DS were irrelevant to speech rate. In addition, the proportion of repetition‐gained errors in serial recall was higher in children with DS than in control subjects. Conclusions The present findings suggest that poor access to long‐term lexical knowledge, rather than overt articulation speed, constrains verbal short‐term memory functions in individuals with DS.     

The stability of inhibitory and working memory deficits in children and adolescents who are children of parents with schizophrenia

Cognitive deficits are a central feature of schizophrenia and occur in first-degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives. This report focuses on 25 children (ages 6-15 years), all with at least one schizophrenic parent. The children were assessed twice, utilizing inhibitory and working memory tasks, with a mean 2.6 years between visits. Stop reaction time (a measure of motor inhibition) and performance on a counting span task (a measure of verbal working memory) were borderline to mildly impaired (compared with a typically developing comparison group) at both visits with similar effect sizes (stopping task time 1, effect size = 0.46, time 2 effect size = 0.50; counting span time 1 effect size = 0.53, time 2 effect size = 0.42). For these 2 tasks, individual age-adjusted scores also correlated across both time points (r = 0.41-0.76) suggesting that individual children maintained deficits across time. As etiologically driven strategies are developed for the cognitive deficits of schizophrenia, expansion of these treatments to relatives who share the cognitive but not the psychotic symptoms may be worth exploring.     

Prevalence of cerebrovascular lesions in Parkinson's disease. A postmortem study

Data on the relationship between Parkinson's disease (PD) and stroke have been conflicting, some studies showing a reduced risk of stroke during life, and others indicating an increased risk of stroke-related death. Consecutive cases (n=617) of autopsy-proven idiopathic PD (Lewy body disease of the brain stem type) and age-matched controls (n=535) were compared using current routine and immunohistochemical methods. The total frequency of cerebrovascular lesions (lacunes, amyloid angiopathy, white matter lesions, old and recent ischemic infarcts and hemorrhages) in PD (44.0%) was higher than in controls (32.8%), while acute, often fatal ischemic or hemorrhagic strokes were less frequent in parkinsonian patients (1.8% vs 2.6%). Like previous postmortem findings in a smaller cohort, these findings neither indicate a protective effect against stroke nor a greater susceptibility to death from stroke in the populations studied. Cognitive impairment in PD appears to be largely independent from coexistent vascular pathology except in cases with severe cerebrovascular lesions.     

Raised plasma oxidised LDL in acute cerebral infarction

BACKGROUND: The association between oxidised low density lipoprotein (OxLDL) and cerebral infarction is suspected but not established. OBJECTIVES: To determine whether plasma OxLDL is a useful marker for monitoring oxidative stress in stroke patients. METHODS: Plasma OxLDL concentrations were determined in 56 stroke patients with cerebral infarction (n = 45) or cerebral haemorrhage (n = 11), and in 19 age matched controls, using a novel sandwich enzyme linked immunosorbent assay. RESULTS: Compared with the controls (0.130 (0.007) ng/ micro g LDL, mean (SEM)), OxLDL was significantly raised in patients with cerebral infarction (0.245 (0.022); p < 0.0001) but not in those with haemorrhage (0.179 (0.023)). Patients with cortical ischaemic infarcts (n = 22) had higher OxLDL levels than either the controls (p < 0.0001) or the patients with non-cortical ischaemic infarcts (n = 23) (p < 0.001). Increased OxLDL concentrations in patients with cortical infarcts persisted until the third day after stroke onset. The National Institutes of Health stroke scales in patients with cortical infarction were higher than in those with non-cortical infarction (p < 0.01). CONCLUSIONS: There is a significant association between raised plasma OxLDL and acute cerebral infarction, especially cortical infarction. Plasma OxLDL may reflect oxidative stress in stroke patients.     

Need for cognitive rehabilitation for children with sickle cell disease and strokes

Stroke is a significant cause of morbidity among children with sickle cell disease (SCD). Approximately 30% of children with sickle cell anemia will have either an overt stroke or silent infarct (an injury to the brain that does not have any focal neurological findings or a history of focal neurological deficits). Despite the strong association between stroke and cognitive deficits and poor educational attainment, few interventions have been developed to address this vulnerable population of children. A cognitive rehabilitation program was piloted to improve the memory and educational achievement of children with sickle cell disease and stroke. While the intervention was feasible, additional research is needed to establish efficacy. Ongoing studies are designed to improve the cognitive impairment for children with SCD and stroke. The health and educational systems will need to work as partners to improve the cognitive and educational outcomes of these children after they suffer from stroke.