The impact of lesion laterality on neuropsychological change following posterior pallidotomy: a review of current findings

This paper reviews seven studies evaluating the impact of lesion laterality on the neuropsychological sequelae of posterior pallidotomy for treatment of Parkinson's disease. Left lesions of the internal globus pallidus (GPi) were associated with subtle deficits on measures sensitive to frontal lobe function. The findings of a randomized clinical trial including a patient control group indicated that many of these deficits were transient, resolving by 6 months following surgery. Right GPi lesions were not consistently associated with neuropsychological deficit, except in one study that included a significant proportion of demented patients. It is hypothesized that when neuropsychological decline is present following surgery, this reflects impingement of posterior GPi lesions into proximal regions such as anterior GPi or the external pallidum that participate in cognitive basal ganglia-thalamocortical circuits. The findings from neuroimaging will be important for elucidating the relationship between lesion locus and neuropsychological sequelae.     

Cognitive deficits following coronary artery bypass grafting: prevalence, prognosis, and therapeutic strategies

There is increasing recognition that coronary artery bypass grafting (CABG) may be a risk factor for subtle cognitive decline although the presence and pattern of such decline has varied across studies. Cognitive deficits may present as short-term memory loss, executive dysfunction and psychomotor slowing. Although they are usually are not severe enough to meet criteria for mild cognitive impairment or vascular dementia, they lower quality of life and add to hospitalization and out-of-hospital costs. Proposed mechanisms include surgical-related trauma, genetic susceptibility (eg, apolipoprotein E4 allele), microembolization, other vascular or ischemic changes, and temperature during surgery. Depression and anxiety levels predict subjective perception of these deficits more than objective cognitive performance. Both nonpharmacologic (eg, emboli reduction, temperature, or glucose management) and pharmacologic (eg, dexanabinol, glypromate, nootropics) strategies to prevent post-CABG cognitive deficits are under investigation. Given the large numbers of subjects who may already have CABG associated cognitive deficits, clinical trials of agents being tested for Alzheimer's disease (eg, donepezil, rivastigmine, memantine, neramexane, ginkgo) may also be informative. The results of multicenter long-term outcome studies (with matched control groups) as well as ongoing treatment trials will more conclusively address some of these issues. These data emphasize the need for clinicians to monitor cognitive function before and after coronary bypass surgery, and to educate patients.     

Subtle cognitive deficits in severe alcohol addicts – Do they show a specific profile?

Although alcohol dependency is a burden to society, data on cognitive performance in therapy‐resistant patients after multiple withdrawals are poor. In this study, 22 patients without reported cognitive deficits and 20 control subjects performed extensive cognitive testing and a motor task assessing short‐term memory. Patients displayed subtle deficits (mainly in executive function), while memory functions were relatively unimpaired. Our results suggest that subtle frontal‐executive deficits may contribute to a poor prognosis, but could be missed by routine clinical tests.     

Neuropsychological Aspects of Pediatric Sickle Cell Disease

Sickle cell disease (SCD), a class of genetic disorders characterized by abnormal, sickled red blood cells, is a chronic illness that results in progressive cerebrovascular disease. Neurocognitive sequelae of clinically apparent cerebrovascular accidents in children with SCD are characterized by pervasive impairments, including decrements in general intellectual functioning, language and verbal abilities, visual-motor and visual-spatial processing, memory, academic achievement, and processing of subtle prosodic information. In contrast, subtle neurocognitive deficits in the areas of attention and concentration, executive function, and visual-motor speed and coordination appear to be associated with silent infarcts that are not necessarily detected on physical examination. Investigation of the disease course and associated neurocognitive sequelae suggest a disease-specific model of neuropsychological impairment. Recommendations are made for clinical and research efforts in the field of pediatric neuropsychology.     

Mild cognitive impairment: a neuropsychological perspective

Mild cognitive impairment (MCI) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia. For the majority of patients, MCI represents a transitional state between normal aging and mild dementia, usually Alzheimer's disease. Multiple subtypes of MCI are now recognized. In addition to presentations featuring memory impairment, symptoms in other cognitive domains (eg, executive function, language, visuospatial) have been identified. Neuropsychological testing can be extremely useful in making the MCI diagnosis and tracking the evolution of cognitive symptoms over time. A comprehensive test battery includes measures of baseline intellectual ability, attention, executive function, memory, language, visuospatial skills, and mood. Informant-based measures of neuropsychiatric symptoms, behaviors, and competency in instrumental activity are also included. Careful assessment can identify subtle deficits that may otherwise elude detection, particularly in individuals of superior baseline intellectual ability. As we move closer to disease-modifying therapy for Alzheimer's disease, early identification becomes critical for identifying patients who have an opportunity to benefit from treatment.     

Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice

Misfolded amyloid beta peptide (Abeta) is a pathological hallmark of Alzheimer's disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of Abeta over-production indicate that Abeta-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those Abeta-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets. Here, we report that the enzymatic activity of calcineurin, a key protein phosphatase involved in phosphorylation-dependent kinase activity crucial for synaptic plasticity and memory function, is upregulated in the CNS of the Tg2576 animal model for Abeta over-production. Furthermore, acute treatment of Tg2576 mice with the calcineurin inhibitor FK506 (10mg/kg i.p.) improves memory function. These results indicate that calcineurin may mediate some of the cognitive effects of excess Abeta such that inhibition of calcineurin shall be further explored as a potential treatment to reverse cognitive impairments in AD.     

The relation of hypertension to cognitive function

Hypertension is an established risk factor for stroke. However, prior to such a major clinical event, hypertension exerts a more subtle impact on the brain that is revealed by diminished cognitive function. Studies comparing the performance of people with high and normal blood pressure levels have shown that high blood pressure or hypertension is related to poorer performance on tests of attention, learning and memory, executive functions, visuospatial skills, psychomotor abilities, and perceptual skills. Hypertension is also predictive of cognitive decline. Variables that may alter (i.e., moderate) the relation of hypertension to cognitive function include age, education, several biological characteristics of hypertension, and the presence of concurrent diseases. Although hypertensives are not clinically impaired, their diminished levels of cognitive performance could affect their perceived quality of life. Various brain mechanisms may explain the relation of hypertension to lower levels of cognitive function. Further understanding of the relation between hypertension and cognition is critical to the preservation of cognitive function across the life span.     

干细胞移植治疗冠心病的现状与未来

冠心病仍然是全球的主要死亡原因。其所造成的心肌梗死及慢性心力衰竭对生活质量的影响和由此造成的高额医疗费用促使我们不断寻求新的医疗措施。近几年有关干细胞用于心肌梗死后心肌再生、心肌内新生血管形成,可能还会改善梗死后的心功能的研究成为心脏病学研究的最热门领域。尽管干细胞治疗有可能使心力衰竭的治疗得到彻底的革命,但仍有部分问题需要澄清。已发表的各个研究结果设计不尽相同,致使对该项治疗的效果较难得出一致的结论。但这些研究都强调干细胞治疗在未来心血管疾病的治疗中可能会发挥较大的作用。干细胞治疗与药学、外科及介入治疗的结合会显著改善冠心病患者的预后。     

Neurocognitive and functional outcomes in persons recovering from West Nile virus illness

Long‐term neurocognitive and functional impairments following West Nile virus (WNV) disease are poorly understood. We assessed quality‐of‐life indices and neurocognitive performance in a cohort of 54 persons recovering from one of three WNV disease syndromes (fever [WNF], meningitis [WNM], or encephalitis [WNE]) approximately 1.5 years following acute illness. We compared findings between the three syndromic groups; the study cohort and a demographically similar group of 55 controls from a study of chronic fatigue syndrome (CFS); and the study cohort and a ‘normative’ control population based on cognitive test data. Persistent symptoms, diminished quality of life, and functional impairment were reported by 50% of WNF patients, and 75% each of WNM and WNE patients. Overall, objective neurocognitive performance did not differ significantly between the three syndromic groups, or between the study cohort and the CFS controls or the normative controls. In some neurocognitive subtests, the study cohort scored below the 15th percentile when compared with normative control data. Most persons who returned to independent living following hospitalization for WNV illness had persistent subjective complaints, but had normal cognitive function. However, a minority displayed subtle neurocognitive deficits more than 18 months following acute disease.     

Neuropsychological Functioning in Chronic Lyme Disease

Lyme disease is currently the most common vector-borne illness in the United States. The disease is multisystemic, and chronic disease, in particular, may be associated with neuropsychological deficits. However, to date, only a few empirical studies exist, which examine the neuropsychological sequelae associated with chronic Lyme disease. A review of the literature shows that the deficits observed in adults with chronic Lyme disease are generally consistent with the deficits that can be seen in processes with primarily frontal systems involvement. These observations are generally consistent with neuroradiologic findings. The clinical presentation in chronic Lyme disease and the nature of the neuropsychological deficits are discussed, as are several central issues in understanding neuropsychological functioning in chronic Lyme disease, such as the impact of chronic illness, response to treatment, and the relationship between neuropsychological performance and depression, fatigue, and neurological indicators of disease.     

Cognitive deficits in compulsive checkers: An exploratory study

Compulsive-checking behavior can be conceptualized as resulting, in part, from a memory failure. In order to determine if memory difficulties are associated with compulsive checking, the performance of college-student checkers were compared with the performance of non-checkers on a number of cognitive tasks hypothesized to be relevant to understanding checking behavior. Using the Checking and Cleaning subscales of the Maudsley Obsessional-Compulsive Inventory, four groups of subjects were identified: (1) Cleaning Checkers (N = 13); (2) Noncleaning Checkers (N = 13); (3) Cleaning Noncheckers (N = 13); and (4) Noncleaning Noncheckers (N = 15). It was hypothesized that the cognitive deficits studied would characterize individuals with cheeking compulsions, but not persons with non-checking compulsions (i.e. Cleaning Noncheckers) or normal controls (i.e. Noncleaning Noncheckers). Compulsive checkers were found to have a poorer memory for prior actions than non-checkers and were also found to underestimate their ability at distinguishing memories of real and imagined events, a process referred to as reality monitoring. Both of these deficits were specific to compulsive checkers and can be viewed as contributing to the likelihood that an individual will engage in checking behavior. If an individual has difficulty in recalling whether an intended action has been executed, they may be inclined to engage in checking behavior to insure the intended action is carried out. Similarly, a tendency to underestimate reality-monitoring ability could result in increased checking behavior as the individual attempts to reduce his/her uncertainty over whether a previous behavior actually occurred or merely was thought to occur. It is concluded that the study of cognitive deficits in compulsive checking is a potentially fruitful avenue for further inquiry.     

Neuropsychologic Deficits in Children with Sickle Cell Disease and Cerebral Infarction: Role of Lesion Site and Volume

Little is known about the correlation between the location and size of cerebral infarction in children and neuropsychologic deficits. We related lesion location and volume on magnetic resonance exams to neuropsychologic performance in 28 children with cerebral infarcts due to sickle cell disease. Seventeen healthy siblings served as a comparison group. Children with anterior cerebral infarcts (n = 7) showed deficits in attention and executive skills, whereas children with more widespread cerebral infarcts (n = 18) showed additional deficits in spatial skills. The volume of cerebral infarction was associated with spatial and language performance, but minimally related to performance in other cognitive domains. The location and volume of cerebral infarction are both important for defining the type and magnitude of cognitive sequelae in childhood stroke.     

Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease

A growing body of evidence suggests that a preclinical phase of Alzheimer's disease (AD) exists several years or more prior to the overt manifestation of clinical symptoms and is characterized by subtle neuropsychological and brain changes. Identification of individuals prior to the development of significant clinical symptoms is imperative in order to have the greatest treatment impact by maintaining cognitive abilities and preserving quality of life. Functional magnetic resonance imaging (fMRI) offers considerable promise as a non-invasive tool for detecting early functional brain changes in asymptomatic adults. In fact, evidence to date indicates that functional brain decline precedes structural decline in preclinical samples. Therefore, fMRI may offer the unique ability to capture the dynamic state of change in the degenerating brain. This review examines the clinical utility of blood oxygen level dependent (BOLD) fMRI in those at risk for AD as well as in early AD. We provide an overview of fMRI findings in at-risk groups by virtue of genetic susceptibility or mild cognitive decline followed by an appraisal of the methodological issues concerning the diagnostic usefulness of fMRI in early AD. We conclude with a discussion of future directions and propose that BOLD-fMRI in combination with cerebral blood flow or diffusion techniques will provide a more complete accounting of the neurovascular changes that occur in preclinical AD and thus improve our ability to reliably detect early brain changes prior to disease onset.     

Working Memory and Learning in Early Alzheimer’s Disease

Cognitive deficits associated with early Alzheimers disease (AD) have been recently operationalised in terms of an acquisition deficit and the research supporting this view is presented. However, there is still debate concerning the nature of this deficit and how underlying cognitive processes may be detrimentally affecting the ability to acquire new information in early AD. This review argues that the pattern of cognitive deficits contributing to the acquisition impairment in early AD patients may be readily interpreted within the context of a working memory model. Isolating the component processes of working memory that underlie the acquisition deficit in early AD patients will aid in the design of clinical applications that are focussed at enhancing the ability to acquire new information in everyday life.     

Subtle Motor Findings During Recovery from Pediatric Traumatic Brain Injury: A Preliminary Report

Pediatric traumatic brain injury (TBI) is a heterogeneous condition, varying in both severity and sequelae. The long-term motor deficits following severe TBI requiring inpatient rehabilitation are better established than those following milder forms of TBI. The authors examined motor performance 2 and 12 months postinjury in children without overt motor impairment using standard measures of upper limb function and the Physical and Neurological Examination for Subtle Signs (PANESS). The PANESS was sensitive to differences between children with TBI and uninjured children as well as to changes in children with TBI over time. These data suggest that subtle motor deficits are present after milder forms of TBI and, particularly those related to balance and gait, may persist even 12 months postinjury.     

Optimizing treatment of schizophrenia. Enhancing affective/cognitive and depressive functioning

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments.     

Cognitive control of saccadic eye movements

The saccadic eye movement system provides researchers with a powerful tool with which to explore the cognitive control of behaviour. It is a behavioural system whose limited output can be measured with exceptional precision, and whose input can be controlled and manipulated in subtle ways. A range of cognitive processes (notably those involved in working memory and attention) have been shown to influence saccade parameters. Researchers interested in the relationship between cognitive function and psychiatric disorders have made extensive use of saccadic eye movement tasks to draw inferences as to the cognitive deficits associated with particular psychopathologies. The purpose of this review is to provide researchers with an overview of the research literature documenting cognitive involvement in saccadic tasks in healthy controls. An appreciation of this literature provides a solid background against which to interpret the deficits on saccadic tasks demonstrated in patient populations.     

Human behaviour and development under high-altitude conditions

Although we are far from a universally accepted pattern of impaired function at altitude, there is evidence indicating motor, perceptual, memory and behavioural deficits in adults. Even relatively low altitudes (2500 m) may delay reaction time, and impair motor function. Extreme altitude exposure (>5000 m) may result in more pronounced impairment that can persist after returning to the lowlands. Research into the effects of altitude exposure earlier in development is lacking by comparison. Un-acclimatized children can suffer from acute mountain sickness, and, in native populations born at altitude, subtle cognitive and behavioural deficits suggest incomplete adaptation to hypoxia. The study of neurobehavioural functioning at altitude may provide important information about the effects of clinical hypoxia on the human brain and behavioural development.     

Cognitive control of saccadic eye movements

The saccadic eye movement system provides researchers with a powerful tool with which to explore the cognitive control of behaviour. It is a behavioural system whose limited output can be measured with exceptional precision, and whose input can be controlled and manipulated in subtle ways. A range of cognitive processes (notably those involved in working memory and attention) have been shown to influence saccade parameters. Researchers interested in the relationship between cognitive function and psychiatric disorders have made extensive use of saccadic eye movement tasks to draw inferences as to the cognitive deficits associated with particular psychopathologies. The purpose of this review is to provide researchers with an overview of the research literature documenting cognitive involvement in saccadic tasks in healthy controls. An appreciation of this literature provides a solid background against which to interpret the deficits on saccadic tasks demonstrated in patient populations.     

Association between biological markers of sickle cell disease and cognitive functioning amongst Cameroonian children

Background: Some of the major complications of sickle cell disease (SCD) occur in the brain and apart from overt stroke, patients also present with cognitive impairments. We sought to evaluate the prevalence of cognitive deficits as well as their biological predicting factors in young SCD patients in Cameroon.

Methods: The cognitive performances of Cameroonian SCD young patients were evaluated using a neuropsychological test battery assessing four domains of cognitive functioning (executive functions, attention, memory, and sensory-motor skills) previously adapted and normalized on healthy subjects in Yaoundé.

Findings: Up to 37.5% of the 96 SCD patients aged 6 to 24 years (M?=?13.5, SD?=?4.9) had mild-to-severe cognitive deficits. The cognitive deficits tend to increase with age. There was a significant effect of SCD on executive functions and attention, whereas SCD patients performed as well as controls on memory and sensory-motor skills tests. Structural equation models showed a significant association between (a) severe anemia and lower executive functioning, (b) low fetal hemoglobin levels and lower executive functioning and attention, (c) history of cerebrovascular accidents and lower performances in executive functioning, sensory-motor skills, and memory, (d) pathological electroencephalogram and lower attention, and (e) abnormal Transcranial Doppler and lower memory.

Conclusion: SCD patients in Cameroon presented a very high prevalence of cognitive deficits, with a specific impairment of executive functions and attention. Routine neuropsychological evaluation for early detection of cognitive deficits in SCD patients could represent a cost-effective tool to implement in resource-limited contexts such as in sub-Saharan Africa.