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.     

Inferior Parietal Perfusion, Lateralization, and Neuropsychological Dysfunction in Alzheimer's Disease

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting¹³³Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence, verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and—paradoxically—verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predictive of cognitive decline in AD. Right-sided deficits, however, may be most important for predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline as measured by most standard neuropsychological measures.     

Central Nervous System Complications of Sickle Cell Disease in Children: An Overview

Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, “silent cerebral infarcts” are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined.     

Central nervous system complications of sickle cell disease in children: an overview.

Complications involving the central nervous system are among the most devastating manifestations of sickle cell disease. Although overt stroke occurs in 1 in 10 children with Hemoglobin SS, "silent cerebral infarcts" are even more frequent. Both are associated with significant neuropsychological deficits. The end result of these effects on the CNS often is diminished school performance. The use of transcranial Doppler ultrasonography screening allows the identification of patients at high risk for clinical stroke as well as stroke prevention by chronic transfusion. However, definitive prophylaxis and treatment for most CNS complications of sickle cell disease have yet to be determined.     

Neuropsychological mediators of the links among age, chronic illness, and everyday problem solving

Reductions in everyday problem solving (EPS) are often reported in older age, although the underlying mechanisms remain unclear. The authors examined the role of 2 variables predicted to mediate (neuropsychological abilities and health status) or moderate (health status) the relationship between age and EPS performance. Toward these ends, they compared EPS and neuropsychological performance in 50 functionally independent adults with chronic kidney disease (CKD) and 64 control participants matched on age and education. Both older age and CKD were associated with worse performance on measures of EPS and memory/executive abilities. Neuropsychological abilities were positively associated with EPS performance. In both the full sample and control participants only, memory/executive functioning mediated the association between presence of chronic illness and EPS. Furthermore, memory/executive functioning partially mediated the link between age and EPS. Findings indicate that relations among age, health status, and EPS are not straightforward. Although performance on neuropsychological measures appeared to underlie EPS declines in chronic illness, increasing age remained independently associated with reduced EPS. The authors discuss implications for models of adult developmental changes in everyday cognition.     

Neuropsychological functioning in hemiparkinsonism

A standardized neuropsychological battery including measures of intellectual cognitive, memory, attention-concentration, language, abstraction and mental flexibility, and sensory and motor functions was administered to 21 hemiparkinsonian patients (14 with right side and 7 with left side symptoms) and 17 controls matched for age and education. Patients were impaired in all functions except sensory. For motor functions, impairment was ipsilateral to the side of symptoms. For cognitive functions, right side symptoms were associated with verbal deficits whereas left side symptoms were associated with spatial deficits. Thus, a pattern of neuropsychological deficits consistent with the lateralization of motor symptoms may appear in the early stages of the disease.     

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.     

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems.     

The Role of Cognitive Deficits in the Development of Eating Disorders

Eating disorders (ED), including anorexia and bulimia nervosa, are chronic illnesses with periods of symptom exacerbation and remission. Because symptoms are usually present from 6 to 24 months before a diagnosis is made, aetiological agents are believed to be active well before symptoms appear. It is proposed that neuropsychological deficits in various cognitive domains preexist and underlie the aetiology of ED. This paper provides a comprehensive review of the literature relevant to neuropsychological deficits in ED patients and explores the relationship between cognitive deficits, psychosocial development, and the development of ED. Although the role of neuropsychological deficits in the evolution of ED requires further research, the proposed association has significant implications for clinical practice.     

Cognitive function after open-heart surgery: Are postoperative neuropsychological deficits caused by cardiopulmonary bypass?

Despite the many technological developments in arterial perfusion and cardiac surgical procedures, open-heart surgery is still believed to pose a significant risk for cerebral injury. There are several potential causes of brain damage during open-heart surgery, including prolonged or severe arterial hypotension, as well as emboli emanating from the cardiopulmonary bypass circuit or the operative field. This article reviews the available neuropsychological studies of outcome following cardiac valve replacement and coronary artery bypass grafting. Because both procedures are life-saving operations, the research in this area has been quasi-experimental and fraught with methodological problems. Nonetheless, the findings converge to suggest that cognitive dysfunction occurs after open-heart surgery, and that the deficits are attributable, at least in part, to factors specific to the operation or to the patient being maintained on cardiopulmonary bypass. Preliminary findings suggest that embolization is the primary cause of perioperative deficits in uncomplicated operations. Studies have also consistently found preoperative deficits in this population, suggesting that neuropsychological dysfunction is caused by severe chronic cardiac disease as well as open-heart surgery.     

Neuropsychological function and memory suppression in conversion disorder

Conversion disorder (CD) is a condition where neurological symptoms, such as weakness or sensory disturbance, are unexplained by neurological disease and are presumed to be of psychological origin. Contemporary theories of the disorder generally propose dysfunctional frontal control of the motor or sensory systems. Classical (Freudian) psychodynamic theory holds that the memory of stressful life events is repressed. Little is known about the frontal (executive) function of these patients, or indeed their general neuropsychological profile, and psychodynamic theories have been largely untested. This study aimed to investigate neuropsychological functioning in patients with CD, focusing on executive and memory function. A directed forgetting task (DFT) using words with variable emotional valence was also used to investigate memory suppression. 21 patients and 36 healthy controls completed a battery of neuropsychological tests and patients had deficits in executive function and auditory‐verbal (but not autobiographical) memory. The executive deficits were largely driven by differences in IQ, anxiety and mood between the groups. A subgroup of 11 patients and 28 controls completed the DFT and whilst patients recalled fewer words overall than controls, there were no significant effects of directed forgetting or valence. This study provides some limited support for deficits in executive, and to a lesser degree, memory function in patients with CD, but did not find evidence of altered memory suppression to support the psychodynamic theory of repression.     

Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection

Schizophrenia, which has both genetic and environmental causes, is associated with persistent symptoms and severe functional disability. The illness lies dormant during the premorbid phase and begins to express itself during adolescence or early adulthood. Clinical progression and deterioration reaches a plateau in which the patient is said to be in the chronic phase of illness and at which point restoration of prior functioning is unlikely. The severe deficits associated with schizophrenia are often the result of progression of illness due to lack of appropriate treatment. However, recent advances in neuropsychiatry have led to very early identification of individuals at risk for psychosis, even during the prodromal stage when psychosis has not yet manifested clinically. While research has demonstrated that the efficacy of antipsychotics is limited when used during the chronic phase of illness, these medications can effectively control symptoms and prevent progression of illness when used during the early stages of illness. The evidence of neural degeneration in the pathophysiology of schizophrenic illness suggests that there may be treatment opportunities through neural protection. Neuroprotection, which refers to treatment that helps maintain central nervous system functionality in response to neurobiologic stress, may be responsible for prevention of disease progression and deterioration. In this monograph, Jeffrey L. Lieberman, MD, introduces the phases of schizophrenic illness in relation to the concepts of progression and deterioration. Next, Dolores Malaspina, MD, reviews the neurodevelopmental and neurodegenerative components of schizophrenia. Finally, L. Fredrik Jarskog, MD, focuses on the neuroprotective aspects of therapeutic interventions in schizophrenia.     

Cognitive and neuropsychological outcomes: more than IQ scores

Improved survival in preterm infants has broadened interest in cognitive and neuropsychological outcomes. The incidence of major disabilities (moderate/severe mental retardation, neurosensory disorders, epilepsy, cerebral palsy) has remained consistent, but high prevalence/low severity dysfunctions (learning disabilities, ADHD, borderline mental retardation, specific neuropsychological deficits, behavioral disorders) have increased. The follow-up literature contains methodologic problems that make generalizations regarding outcome difficult, and these are discussed. Although mean IQs of former VLBW infants generally are in the low average range and are 3-9 points below normal birth weight peers, these scores mask subtle deficits in: visual-motor and visual-perceptual abilities, complex language functions, academics (reading, mathematics, spelling and writing), and attentional skills. There is an increased incidence of non-verbal learning disabilities, need for special educational assistance, and behavioral disorders in children born prematurely. Males have more problems, and there is a trend for worsening outcome over time, due to emergence of more subtle deficits in response to increased performance demands. In addition to IQ and achievement testing in follow-up, there should be evaluation of executive functions and attention, language, sensorimotor functions, visuospatial processes, memory and learning, and behavioral adjustment.     

Cognitive Effects of HIV-1 Infection

The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.     

Neuropsychological Functioning in Early Hydrocephalus: Review From a Developmental Perspective

Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child’s functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.     

Neuropsychological functioning in early hydrocephalus: review from a developmental perspective.

Children with hydrocephalus have deficits in several neuropsychological domains. The most notable are motor, visuoperceptual, and visuomotor function. These deficits are multiply determined and depend on the etiology and severity of the hydrocephalus to a large extent. Corpus callosum abnormalities resulting from stretching of callosal fibers and other cortical white matter tracts are implicated as contributory to these deficits. Enlarged ventricles and associated compression of posterior cortical areas also correlate with cognitive impairment. Distinguishing which cognitive domain negatively impacts on the child's functioning and which domains influence behavior in isolation or in combination has been the subject of numerous studies. Developmentally, we know little about the emergence of neuropsychological functioning in children with hydrocephalus. Study of the effects of hydrocephalus at different stages of development is useful to clinicians and researchers interested in the impact of diffuse neurophysiological damage on cognition in the developing brain. The medical and neuropsychological literature have begun to inform about these effects. The core deficits in hydrocephalus have yet to be explicated and a focus on investigations that answer these questions is required. This review summarizes the current knowledge about neurocognitive sequelae of hydrocephalus.     

Stress, Coping and Cognitive Deficits in Women After Surgery for Breast Cancer

Research on neuropsychological difficulties among cancer patients has focused on chemotherapy as a primary cause, yet several studies have now shown that some patients evidence cognitive weaknesses prior to chemotherapy. As an alternative to the ‘chemo–brain’ theory, this study examined the hypothesis that stress and coping style may be associated with observed neuropsychological difficulties among female cancer patients. Thirty-six women completed neuropsychological testing and psychological questionnaires following surgery for breast cancer and prior to any subsequent treatments. Twenty-seven percent of participants evidenced deficits on at least one measure of verbal fluency, and 14% of participants were impaired on at least one memory measure. Self-reported stress was correlated with deficits in memory, verbal fluency, and attention. Subsequent mediational analyses indicated that use of passive coping styles may underlie this relationship between stress and neuropsychological deficits. These findings highlight the potential relevance of psychological mechanisms, such as coping style, in cancer patients’ experience of neuropsychological deficits.     

Cognitive deficits related to major organ failure: The potential role of neuropsychological testing

Until recently, little attention has been paid to the possibility of cognitive deficits in patients with disease or failure of major organs such as the liver, kidney, or heart. However, there is a growing awareness that major organ failure often has neuropsychological sequelae. These sequelae may at times be quite subtle and not detectable under gross. examination. Nevertheless, even subtle deficits may have a major impact on adherence to medical regimens, psychosocial adjustment, and quality of life of patients. Neuropsychological assessment has a potentially valuable role to play both in research and in clinical work. It can be useful in adding to our knowledge of the cognitive effects of various types, severity and duration of major organ disease, as well as sequelae associated with treatment. It also is a potentially valuable clinical tool for identifying cognitive deficits that will affect the quality of life and probability of survival for organ failure patients.     

Neuropsychological Effects of Brain Arteriovenous Malformations

Brain arteriovenous malformations (AVM's) are developmental, chronic lesions that provide unique information about the human brain and can be a useful model for neuroscientists to study cerebral reorganization and hemodynamics. We review the neuroanatomy, epidemiology, natural history, imaging and treatment of brain AVMs, and provide a model with which to better understand neuropsychological functioning and brain reorganization. We suggest that future studies must exclude ruptured AVMs if they wish to further explain focal neurological/cognitive deficits associated with this neurovascular anomaly.     

Turning it Upside Down: Areas of Preserved Cognitive Function in Schizophrenia

Patients with schizophrenia demonstrate marked impairments on most clinical neuropsychological tests. These findings suggest that patients suffer from a generalized form of cognitive impairment, with little evidence of spared performance documented in several large meta-analytic reviews of the clinical literature. In contrast, we review evidence for relative sparing of aspects of attention, procedural memory, and emotional processing observed in studies that have employed experimental approaches adapted from the cognitive and affective neuroscience literature. These islands of preserved performance suggest that the cognitive deficits in schizophrenia are not as general as they appear to be when assayed with clinical neuropsychological methods. The apparent contradiction in findings across methods may offer important clues about the nature of cognitive impairment in schizophrenia. The documentation of preserved cognitive function in schizophrenia may serve to sharpen hypotheses about the biological mechanisms that are implicated in the illness.