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Retest effects and cognitive decline in longitudinal follow-up of patients with early HD.

OBJECTIVE: To assess the natural progression of cognitive impairment in Huntington's disease (HD) and to reveal factors that may mask this progression. BACKGROUND: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. METHODS: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 +/- 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). RESULTS: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. CONCLUSION: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Adult↗

Profile of executive and memory function associated with amphetamine and opiate dependence.

Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices.

Adult↗

Influence of cognitive functioning on functional status in an older population: 3- and 6-year follow-up of the Maastricht Aging Study.

BACKGROUND: To date, it remains unclear to what extent cognitive competence is related to a change in general functional status in older adults. OBJECTIVES: To evaluate both the cross-sectional and the longitudinal relation between cognitive functioning and functional status. METHODS: Sensorimotor speed, memory, and executive functioning were assessed in a large population of healthy adults aged 60 years and older (n = 485) who participated in the Maastricht Aging Study. Data from the baseline (1993-1995), three-year follow-up, and six-year follow-up were used. Functional status was measured using the SF-36, which was coded into a physical and a mental component summary measure. RESULTS: After adjustment for age, sex, and educational level, a high level of cognitive functioning appeared to be associated with better functional status in the cross-sectional analysis. Longitudinal analyses demonstrated, that cognitive functioning was not a predictor of functional status three or six years later. CONCLUSIONS: Thus while cognitive functioning is useful clinically for predicting the short-term functional status of an older person, it is not useful for predicting that person's long-term (>3 years) functional status and thus the period of validity of the results of these tests in answering such questions is limited.

Aged↗

Verbal repetition in patients with Alzheimer's disease who receive donepezil.

BACKGROUND: Current outcome measures for Alzheimer's disease (AD) drugs have been criticized as insufficiently patient-centred. One commonly unmeasured goal of patients and caregivers is verbal repetition. OBJECTIVES: We examined how often reducing repetition (of questions, statements or stories) was set as treatment goal, whether and when it responded, and how change in repetition correlated with change in other domains. METHODS: This is a secondary analysis of the open-label Atlantic Canada Alzheimer's Disease Investigation of Expectations study of donepezil for mild-moderate AD in 100 community-dwelling people. Goal Attainment Scaling, an individualized account of the goals of treatment, was the primary outcome measure. RESULTS: Reducing repetition was a treatment goal in 46%, who were not systematically different from others. Of 18 patients in whom repetition improved for 9 months, 83% (15) showed a response at 3 months. Early (3-month) response correlated best with the overall level of goal attainment (r = 0.74) and changes in leisure activities (r = 0.69) and social interactions (r = 0.68) compared with changes in cognition (r = 0.44) or behaviour (r = 0.11). Correlations with the ADAS-Cog and MMSE change scores remained only modest (at 12 months = -0.25 and 0.19, respectively). Correlations with the CIBIC-Plus were higher (-0.47 at 3 months and -0.43 at 12 months). CONCLUSION: Diminution of repetition is common, and appears to mark response to cholinesterase inhibition in some patients. Responders generally also show improved cognition and function, perhaps as an aspect of improved executive function.

Aged↗

Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms.

Depressed outpatients having primarily psychological or vegetative symptoms, as defined by the factor analytically developed Hamilton Depression Scale superfactors described by Rhoades and Overall (1983), were compared with similarly aged normal controls on a comprehensive neuropsychological battery. The vegetative group evidenced poorer performance than controls on several measures associated with right hemisphere functioning and on a task associated with executive functioning. In contrast, the psychological group did not significantly differ from controls on any measure, and had significantly better performance than the vegetative group on several tasks. These findings suggest that neuropsychological deficits associated with depression may be limited to those patients with primarily vegetative symptoms.

Aged↗

Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.

Adolescent↗

Assessment of the dysexecutive syndrome in schizophrenia.

BACKGROUND: Cognitive neuropsychological theories hypothesize a role for frontal lobe executive deficits in the aetiology of schizophrenic symptoms. The study examined the performance of a schizophrenic group on the Behavioural Assessment of the Dysexecutive Syndrome (BADS; Wilson et al. 1996), a test battery which assesses the 'everyday' difficulties associated with the dysexecutive syndrome. Performance of the schizophrenics was contrasted with that of brain injured and healthy volunteer groups. METHODS: Matched groups of 31 schizophrenic patients, 35 patients with brain injuries and 26 healthy volunteers were administered the BADS. Patients were also given tests of general intelligence and memory. Patients and their relatives/carers also completed a questionnaire rating day-to-day failures of executive functioning. RESULTS: Schizophrenic and brain-injured patients showed impairment on the BADS, compared to healthy controls. There were no significant differences between the two patient groups. Significant impairment was found in a subgroup of 16 schizophrenics who showed otherwise intact general intellectual functioning, suggesting the existence of a specific executive deficit. Among the schizophrenic patient group there was evidence of a dissociation between executive and memory impairments. A significant correlation existed between performance on the BADS and relatives ratings of executive problems for the brain injured group, but not for the schizophrenic group. CONCLUSIONS: The BADS is a useful tool for identifying executive deficits in people with a diagnosis of schizophrenia, especially those who are otherwise generally intellectually intact. This is particularly important in the context of rehabilitation and community transition programmes.

Adult↗

Emotional and cognitive sequelae to mild traumatic brain injury.

This study compared the emotional functioning and cognitive abilities (i.e., verbal fluency, executive functioning, memory, and attention) of 27 patients with mild traumatic brain injury (MTBI) to that of 27 controls. With the exception of verbal fluency, the cognitive abilities of the MTBI group appeared to be intact. Emotional functioning was assessed using the Neuropsychology Behavior and Affect Profile (NBAP), a revised version of the Neurobehavioural Rating Scale and the Headley Court Psychosocial Rating Scale. The NBAP demonstrated good internal reliability, criterion validity, and construct validity. The MTBI group showed significantly higher levels of post injury depression than controls on the NBAP. Pre injury levels of depression in the MTBI group were also higher than the controls but both the patient reports and those of family members confirmed an increase in depression following MTBI.

Adolescent↗

A meta-analysis of the relative sensitivity of neuropsychological screening tests.

The National Institute of Mental Health recently formed a committee of experts which published a proposal for a lengthy neuropsychological test battery judged most apt to detect diffuse brain damage while covering a wide range of cognitive abilities. The purposes of the present study were (1) to assemble empirical evidence of the existence of statistically significantly sensitive screening tests across an equivalently wide range of functional domains, and (2) to present this evidence systematically, in such a manner as to help clinicians select subsets of screening tests manifesting greatest sensitivity to diffuse brain damage. It was found that in certain functional domains (speed of processing, problem solving, executive functions), marked differences in sensitivity occurred. Brief tests just as sensitive as time-consuming tests were also identified. The reader is cautioned about possible extraneous sources of the differences obtained (test and group selection bias, test reliability, test difficulty, procedural effects, Type I error). Nevertheless, it was concluded that a brief highly sensitive and functionally wide-ranging neuropsychological test battery for screening cases of putative diffuse brain dysfunction can be assembled.

Attention↗

Neuropsychological functioning during the year following severe traumatic brain injury.

The neuropsychological functioning of a group of 65 adults with severe traumatic brain injury was assessed at 6 months and 1 year post-injury. The cognitive domains assessed were pre-morbid intellectual level, current level of general intellectual functioning, simple and complex attention, verbal memory, executive functioning, and perceptual functioning. At least 40%, and up to 74%, of the TBI patients displayed some degree of impairment on tests administered at 6 months. Improvement was found to occur in all areas of cognitive functioning over the first year following injury. Despite this improvement at least 31%, and up to 63%, of TBI patients displayed some degree of impairment on tests administered at 1 year post-injury. The various types of neuropsychological functioning were affected to different degrees, indicating that different aspects of cognition are more susceptible to injury, and that recovery takes place at a differential rate across functions. The implications of these findings for the appropriate planning and allocation of treatment and rehabilitation resources, and the development of effective rehabilitation interventions are outlined.

Adolescent↗

Fractionating attentional control using event-related fMRI.

Despite numerous functional neuroimaging and lesion studies of human executive function, the precise neuroanatomical correlates of specific components of attentional control remain controversial. Using a novel approach that focused upon volunteer behavior rather than experimental manipulations, specific components of attentional shifting were fractionated, and their neural correlates differentiated using event-related fMRI. The results demonstrate that the ventrolateral prefrontal cortex is involved in switching attention "between" stimulus dimensions, whereas the posterior parietal cortex mediates changes in stimulus-response mapping. Furthermore, reversals based on negative feedback activated the lateral orbitofrontal cortex, whereas positive feedback modulated activity in the medial orbital frontal cortex. Finally, the dorsolateral prefrontal cortex was active throughout solution search. These findings support the hypothesis that lateral prefrontal, orbital, and parietal areas form a supervisory network that controls the focus of attention and suggests that these regions can be fractionated in terms of their specific contributions.

Attention↗

Sensory gating impairment in development of post-concussive symptoms in mild head injury.

Post-concussive symptoms reported by mild head injury (MHI) patients have been inadequately understood. Post-concussive symptoms reported by patients with MHI have so far been explained in terms of impairment in neurocognitive functions or deficits in modulation of flow of information. There are no studies that have looked into sensory gating impairment in MHI and its relation to post-concussive symptoms. The purpose of the present paper was to investigate the role of sensory gating impairment in post-concussive symptoms in mild head injury patients. Thirty MHI patients were evaluated for their neuropsychological functions, sensory gating deficits, and post-concussive symptoms. Neuropsychological functions were in the domain of attention, executive functions, and learning and memory. Sensory gating was assessed by Structured Interview for Assessing Perceptual Anomalies and post-concussive symptoms were assessed using the Neurobehavioral Rating Scale. Multiple regression method was used to identify predictors for post-concussive symptoms. Post-concussive symptoms were predicted by sensory gating deficits when sensory gating deficit was one of the predictors along with neuropsychological functions. Post-concussive symptoms were predicted by scores of Digit Vigilance and Digit Symbol Substitution Test, when predictors were restricted to neuropsychological functions. Sensory gating deficits were correlated with performance on Digit Symbol Substitution test. Post-concussive symptoms reported by MHI patients are the result of poor modulation of incoming sensory information.

Adolescent↗

Executive dysfunction in spinocerebellar ataxia type 1.

Fourteen patients with spinocerebellar ataxia 1 (SCA1) and 11 controls with similar mean age and IQ estimates were submitted to a neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory as well as executive functions. Neuropsychological assessment yielded verbal memory and executive dysfunction while tests of visuospatial memory and attention were not significantly impaired in SCA1 as compared to controls. Test performance was neither related to the repeat length, the age of onset nor the disease duration. The profile of cognitive impairment in SCA1 with prominent executive dysfunction corresponds to the concept of "frontal-subcortical" dementia that is likely to be contingent upon disruption of a cerebrocerebellar circuitry that consists of afferent and efferent connections between the prefrontal cortex and the cerebellum.

Adult↗

A computational model of prefrontal control in free recall: strategic memory use in the California Verbal Learning Task.

Several decades of research into the function of the frontal lobes in brain-damaged patients, and more recently in intact individuals using function brain imaging, has delineated the complex executive functions of the frontal cortex. And yet, the mechanisms by which the brain achieves these functions remain poorly understood. Here, we present a computational model of the role of the prefrontal cortex (PFC) in controlled memory use that may help to shed light on the mechanisms underlying one aspect of frontal control: the development and deployment of recall strategies. The model accounts for interactions between the PFC and medial temporal lobe in strategic memory use. The PFC self-organizes its own mnemonic codes using internally derived performance measures. These mnemonic codes serve as retrieval cues by biasing retrieval in the medial temporal lobe memory system. We present data from three simulation experiments that demonstrate strategic encoding and retrieval in the free recall of categorized lists of words. Experiment 1 compares the performance of the model with two control networks to evaluate the contribution of various components of the model. Experiment 2 compares the performance of normal and frontally lesioned models to data from several studies using frontally intact and frontally lesioned individuals, as well as normal, healthy individuals under conditions of divided attention. Experiment 3 compares the model's performance on the recall of blocked and unblocked categorized lists of words to data from Stuss et al. (1994) for individuals with control and frontal lobe lesions. Overall, our model captures a number of aspects of human performance on free recall tasks: an increase in total words recalled and in semantic clustering scores across trials, superiority on blocked lists of related items compared to unblocked lists of related items, and similar patterns of performance across trials in the normal and frontally lesioned models, with poorer overall performance of the lesioned models on all measures. The model also has a number of shortcomings, in light of which we suggest extensions to the model that would enable more sophisticated forms of strategic control.

Brain Injuries↗

Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain and behavior.

Fetal alcohol spectrum disorders constitute a major public health problem. This article presents an overview of important issues that surround these disorders and emphasizes the structural and neurobehavioral consequences associated with prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible moderating factors for the range of outcomes are mentioned. In addition, the prevalence of fetal alcohol spectrum disorders is described, and estimates of the financial impact of these disorders are given. Heavy prenatal alcohol exposure can severely affect the physical and neurobehavioral development of a child. Autopsy and brain imaging studies indicate reductions and abnormalities in overall brain size and shape, specifically in structures such as the cerebellum, basal ganglia, and corpus callosum. A wide range of neuropsychological deficits have been found in children prenatally exposed to alcohol, including deficits in visuospatial functioning, verbal and nonverbal learning, attention, and executive functioning. These children also exhibit a variety of behavioral problems that can further affect their daily functioning. Children exposed to alcohol prenatally, with and without the physical features of fetal alcohol syndrome, display qualitatively similar deficits. Determining the behavioral phenotypes that result from heavy prenatal alcohol exposure is critical, because the identification of these children is crucial for early interventions. In addition, knowing which brain areas are involved might enable the development of better intervention strategies. However, intervention needs to go beyond the affected individual to prevent future cases. As evidenced by the staggering financial impact these disorders have on society, prevention efforts need to be aimed at high-risk groups, and this issue needs to be made a high priority in terms of public health.

Alcohol Drinking↗

Cognitive impairment associated with toxigenic fungal exposure: a replication and extension of previous findings.

In this study, neuropsychological data and symptom reports from 31 individuals exposed to toxic mold were examined. Most participants were found to have reduced cognitive functioning in multiple domains, with memory and executive functions the most commonly affected areas. Rates of dysfunction were significantly greater than chance on more than half of the tests. Number of cognitive impairments was found to be related to depression, although few neuropsychological test scores were correlated with depression. Results also indicated that symptom report of the mold-exposed participants was not significantly different from that of matched groups of 65 persons with mild traumatic brain injury (TBI) and 26 individuals with moderate TBI. The mold-exposed participants reported significantly more symptoms than 47 people with no disability. This study adds to a growing body of literature (e.g., Baldo, Ahmad, & Ruff, 2002; Gordon, Johanning, & Haddad, 1999) relating exposure to mycotoxins to cognitive dysfunction.

Adult↗

Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates.

We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age at onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD.

Adult↗

[Neuropsychology and cognitive deterioration in epilepsy].

OBJECTIVE: To carry out a critical evaluation of the international literature on the neuropsychology of epilepsy. The variables which lead to cognitive deterioration in epilepsy and the effect on cognition of different treatments available (pharmacological and surgical). DEVELOPMENT: We evaluate the influence of different neurological variables on the higher functions (aetiology, age of onset, type of crises, duration of illness, frequency and anti-epileptic drugs). We also describe the cognitive functions most affected in epilepsy (memory, attention, executive function, language). Studies of the surgery of epilepsy show that this may lead to both beneficial and undesirable effects on cognition. CONCLUSIONS: The variables which in general most affect higher functions are the duration of the illness and the frequency and types of crises. The commonest neuropsychological effects are those of memory deficit. These studies show that neuropsychological studies should be done from the time of onset of the disorder. Finally, from the surgical point of view, young patients with considerable crisis reduction or free of crises, with moderate preoperative deterioration of memory have the greatest possibility of post-operative improvement in cognition. Older persons with intact cognitive function and major surgical resection have more possibilities of post-surgical deterioration.

Anticonvulsants↗