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Long-term cognitive effects of Lyme disease in children.

Most studies of adults infected with Lyme disease (LD) have found adverse cognitive effects from the disease. In contrast, the only controlled study investigating cognitive effects of LD in a pediatric population found no effects after a 2-year follow-up. However, it was questioned whether the negative effects might take longer than 2 years to emerge. Therefore, this investigation reports a 4-year follow-up of the original sample. Twenty-five children with strictly defined LD were compared with 17 sibling control children. A neuropsychological battery was utilized, including assessment of the cognitive areas of IQ, information processing speed, fine-motor dexterity, novel problem solving and executive functioning, short-term and intermediate memory, and acquisition of new learning. In addition, parents' subjective ratings were obtained on the disease's impact on their child's participation in everyday activities. No between-group differences were found for 17 of the 18 neuropsychological test measures, nor were there differences in parents' subjective ratings. Therefore, in contrast with studies of adults with LD, the results of long-term follow-up of the pediatric population continue to strongly support the finding that children treated appropriately for LD have an excellent prognosis for normal cognitive functioning.

Adolescent↗

Neurobehavioral effects of acute exposure to inorganic mercury vapor.

Mercury has well-established toxic effects on the central nervous system. This article describes comprehensive neuropsychological and emotional functioning of a group of 13 workers exposed to inorganic mercury vapor compared to that of a normal control group. The exposed group was exposed over a 2- to 4-week period and had elevated blood mercury levels. The evaluations were conducted between 10 and 15 months after exposure was terminated. Observed cognitive deficits included impairment in the following domains: motor coordination, speeded processing with and without a motor component, cognitive flexibility, verbal fluency, verbal memory, and visual problem solving and conceptualization. Emotional problems included increased focus on physical functioning, depression, anxiety, and social withdrawal. Cognitive deficits were, for the most part, not significantly associated with the degree of depression present.

Acute Disease↗

WAIS-III and WMS-III profiles of mildly to severely brain-injured patients.

Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III; The Psychological Corporation, 1997) scores of patients with mild traumatic brain injury (MTBI, n = 23) to moderate-severe traumatic brain injury (M-S TBI, n = 22) were compared to those of 45 matched normal control patients. WAIS-III results revealed that IQ and index scores of MTBI patients did not significantly differ from those of controls, whereas M-S TBI patients received significantly lower mean scores on all measures. All M-S TBI patients' WMS-III index scores also revealed significantly lower scores in comparison to those of control participants, with the exception of Delayed Auditory Recognition. MTBI patients showed significantly lower mean index scores compared to normal controls on measures of immediate and delayed auditory memory, immediate memory, visual delayed memory, and general memory. Eta-squared analyses revealed that WMS-III visual indexes and WAIS-III processing speed showed particularly large effect sizes. These results suggest that symptomatic MTBI patients obtain some low WMS-III test scores comparable to those of more severely injured patients.

Adolescent↗

Construct validity of the 7/24 spatial recall test.

This investigation was conducted to examine the construct validity of the 7/24 Spatial Recall Test (7/24). Participants were 64 outpatients who met criteria for clinically definite multiple sclerosis (MS). Data obtained from administration of a fixed neuropsychological assessment battery were analyzed to evaluate the relation between demographic, physical, and emotional factors and performance on the 7/24, to examine the measure's convergent/discriminant validity, to determine which variables account for the greatest proportion of variance in 7/24 scores, and to assess further the test's sensitivity to the cognitive sequelae of MS. Findings suggest that 7/24 scores are significantly explained by the constructs of visual-spatial perception/analysis, memory, reasoning, and/or processing speed. The proportion of variance in 7/24 performances accounted for by cognitive and demographic variables, however, was quite low. Relative to the measure's normative sample, participants in this investigation performed significantly poorer on number of responses recalled across Set A learning trials but not on Set A long-delay recall. Results of this investigation indicate some level of sensitivity of the 7/24 to the cognitive impairments associated with MS but offer only weak support for the 7/24 as a valid measure of visuospatial learning/memory.

Adult↗

HUMANS: An English and Spanish neuropsychological test battery for assessing HIV-1-infected individuals--initial report.

A neuropsychological battery for testing HIV-1-infected individuals in Spanish was developed. We refer to this battery as the HIV/University of Miami Annotated Neuropsychological test battery in Spanish (HUMANS). The HUMANS battery includes recommendations of the National Institute of Mental Health Neuropsychology Workgroup on HIV-1 infection and measures processes in the following 7 cognitive domains: attention, verbal and visual memory, information processing speed, abstraction and executive functioning, language, visuospatial and visuoconstructive, and motor. Administration requires approximately 3 to 4 hr. The English version of the battery is sensitive to HIV-1 serostatus and Centers for Disease Control clinical disease stage. We report on the test selection, translation, and adaptation of this parallel English battery into Spanish using methods to eliminate linguistically and culturally biased items in some tests. The importance of standardized neuropsychological instruments equivalent in different languages to test HIV-1-positive individuals for impairment is emphasized. Validation and reliability studies are in progress.

Cognition Disorders↗

Adolescent neuropsychological development after early right prefrontal cortex damage.

Adolescent development and pattern of recovery are described for a 15-year-old boy who sustained extensive right dorsolateral prefrontal cortex damage at age 7 from rupture and surgical treatment of a deep arteriovenous malformation. Follow-up evaluations at 4 years and most recently 8 years after illness have shown clear improvement in social-behavioral and almost all cognitive areas initially assessed. He demonstrated resolution of left hemispatial neglect and other visuospatial impairments in working memory, design fluency, and planning and organization. However, at the 8-year follow-up interval, an acquired form of attention deficit disorder remains evident. We hypothesized that this is the likely cause of comparatively lower scores in general intelligence, verbal learning and memory, discourse, and processing speed, that at the 4-year follow-up interval. New measures of emotional face and voice recognition showed only minor difficulties, principally in identifying vocal disgust and fear. Social and psychological maturation has continued to improve, with no evidence of developmental arrest or pervasive social impairment, although the individual is confused at times by complexities and nuances of social interaction. The pattern of findings 8 years after early right dorsolateral prefrontal cortex damage suggests remarkable recovery of primary visuospatial and social impairments, but lingering and somewhat worsening performance deficits which may be due to attentional difficulties and impulsive responding. Treatment of the attentional difficulties is currently being investigated.

Adolescent↗

Effect of low levels of serum vitamin B12 and folic acid on cognitive performance in old age: a population-based study.

We studied the effect of low levels of vitamin B12 and folic acid, alone or combined, on cognitive performance in a population-based sample of 698 older adults (mean age = 68.7 years). No evidence was found for a vitamin-related memory deficit, but research participants with low levels of vitamin B12 exhibited reduced information processing speed relative to participants with normal vitamin B12 levels.

Aged↗

Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with highly active antiretroviral therapy (HAART).

In today's era of highly active antiretroviral therapy (HAART), few children with HIV-1 infection experience severe central nervous system (CNS) manifestations indicative of encephalopathy. However, little is known about the neurocognitive strengths and weaknesses of HIV-infected children treated with HAART. This cross-sectional study is the first to systematically investigate the relation between cognitive functioning and medical markers in HIV-infected children and adolescents treated with HAART with varying levels of computed tomography (CT) brain scan abnormalities. The Wechsler Intelligence Scale for Children-Third Edition was administered to 41 vertically infected children (mean age = 11.2 years) treated with HAART for at least 1 year. Other procedures at the time of testing included CT brain scans and collection of CD4 cell counts and plasma HIV1 RNA PCR. Although global cognitive functioning among participants was in the Average range, children with minimal to moderate CT brain scan abnormalities scored significantly lower than children with normal scans on composite measures of cognitive functioning and five specific subtests, especially tasks involving executive functions. Furthermore, children with worse immune status (CD4+ counts < or = 500) scored lower on subtests measuring processing speed. Viral load was unrelated to cognitive test scores. Thus, children with HIV being treated with HAART remain at risk for developing CNS disease. Findings emphasize the importance of conducting neuropsychological assessments in this population, particularly for children with cortical atrophy and absolute CD4+ cell counts < or = 500.

Adolescent↗

Delayed-execute prospective memory performance: the effects of age and working memory.

This study follows the novel delayed-execute prospective memory paradigm, which involves briefly delaying the execution of an intended action, a task that has been shown to produce substantial age effects. During the ongoing task, sentences were presented, and participants had to answer reading-comprehension questions and general knowledge questions. In the prospective memory task, the participant was to press a key after the presentation of a specific cue in the sentences-but not before a subsequent phase of the ongoing task was reached. In contrast to previous studies using older participants taken from very broadly defined age ranges, this study examines development of delayed-execute prospective memory more precisely by examining a total of 4 age groups: a younger age group (age range = 22-31; n = 27), a young-old age group (age range = 60-69; n = 34), a middle-old age group (age range = 70-79; n = 31), and an old-old age group (age range = 80-91; n = 35). This study investigates the dependence of (age-related) delayed-execute prospective memory performance on working memory capacity by disrupting the phonological loop during the delay period as well as its dependence on neuropsychological processes such as inhibitory control and processing speed. The results show that (a) delayed-execute prospective memory particularly declines within the group of older participants, (b) delayed-execute prospective memory is diminished when working memory load is high during the delay period, and (c) age-related performance in delayed-execute prospective memory may be mediated by inhibitory control. The findings are discussed in the context of the frontal lobe hypothesis of cognitive aging.

Adult↗

Cognitive functions in children at risk for congenital adrenal hyperplasia treated prenatally with dexamethasone.

CONTEXT AND OBJECTIVE: In Sweden, from 1985 through 1995, 40 fetuses at risk for congenital adrenal hyperplasia (CAH) were treated with dexamethasone (DEX) to prevent virilization of affected females. We report long-term effects on neuropsychological functions and scholastic performance of this controversial treatment. DESIGN AND PATIENTS: Prenatally treated children, 7 to 17 yr old, were assessed with standardized neuropsychological tests (A Developmental Neuropsychological Assessment and Wechsler Intelligence Scales for Children) and child-completed questionnaires measuring self-perceived scholastic competence (Self-Perception Profile for Children). A parent-completed questionnaire (Child Behavior Checklist/4-18 School Scale) was used to evaluate whether the treatment had any impact on the children's school performance. In addition, a child-completed questionnaire measuring social anxiety (The Social Anxiety Scale for Children-Revised) was completed by the prenatally treated children aged 8 to 17 yr (n = 21) and age- and sex-matched controls (n = 26). RESULTS: Of 40 DEX-treated children, 26 (median age, 11 yr) participated in the study. Thirty-five sex- and age-matched healthy children were controls. There were no between-group differences concerning psychometric intelligence, measures of cerebral lateralization, memory encoding, and long-term memory. Short-term treated, CAH-unaffected children performed poorer than the control group on a test assessing verbal working memory (P = 0.003), and they rated lower on a questionnaire assessing self-perception of scholastic competence (P = 0.003). This group also showed increased self-rated social anxiety assessed by The Social Anxiety Scale for Children-Revised (P = 0.026). Prenatally treated, CAH-affected children performed poorer than controls on tests measuring verbal processing speed, although this difference disappeared when controlling for the child's full-scale IQ. CONCLUSIONS: This study indicates that prenatal DEX treatment is associated with previously not described long-term effects on verbal working memory and on certain aspects of self-perception that could be related to poorer verbal working memory. These findings may thus question future DEX treatment of congenital adrenal hyperplasia. Therefore, we encourage additional retrospective studies of larger cohorts to either confirm or challenge the present findings.

Adolescent↗

The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients.

OBJECTIVE: To characterize the neuropsychological profile of vascular cognitive impairment (VCI) and vascular dementia (VaD). METHODS: The authors examined 170 patients with stroke or TIA at 3 to 6 months after the vascular event, and 96 age-matched healthy controls, with detailed neuropsychological and medical-psychiatric assessments, with a majority (66.7%) undergoing MRI brain scans. The subjects were diagnosed as having VaD, VCI, or no cognitive impairment by consensus. The neuropsychological tests were classified into cognitive domains, and composite z-scores adjusted for age and education. RESULTS: VaD subjects had disturbance in all cognitive domains, with verbal memory, especially retention, being less affected. VCI subjects had similar but less severe disturbance. The domains that best discriminated cognitively impaired from unimpaired patients were abstraction, mental flexibility, information processing speed, and working memory. Cognitive impairment had a significant correlation with deep white matter hyperintensities, but not with volume and number of infarctions, even though the VaD subjects had larger infarct volumes than VCI subjects. The MRI variables did not provide additional discrimination between subgroups. CONCLUSIONS: The cognitive deficits in VaD and VCI are characterized by disturbance of frontal functions, with less verbal memory impairment. VaD and VCI differ in severity but not pattern of disturbance. The brain lesions that best account for these deficits are noninfarct subcortical white matter and gray matter changes due to ischemia. The picture of VaD/VCI presented shows subcortical deficits embellished by cognitive deficits from cortical infarctions.

Aged↗

Neuropsychological assessment of patients with late onset GM2 gangliosidosis.

OBJECTIVE: To characterize cognitive status in a sample of individuals with late-onset GM2 gangliosidosis (commonly referred to as late-onset Tay-Sachs disease). METHODS: Seventeen subjects (13 men, 4 women) diagnosed with GM2 gangliosidosis were evaluated. Subjects ranged in age from 18 to 56 years and were in various stages of disease progression. Subjects underwent comprehensive neuropsychological assessment. Impairment was defined as performance more than 1.6 SD below the normative mean. RESULTS: Group mean performance was within the denoted normal range on all measures except on a task assessing visual sequencing and set shifting. Approximately one-half of the sample scored in the impaired range on measures of processing speed, visual sequencing, and set shifting. One-third of the sample also scored in the impaired range on measures of delayed verbal recall. Impairment tended to be restricted to a subset of the sample, as 5 of the 14 subjects able to undergo formal testing accounted for 70% of the total number of impaired scores. If the three subjects unable to participate in formal testing are also considered impaired, 47% of the current sample exhibited significant cognitive impairment in at least one cognitive domain. CONCLUSION: In late-onset GM2 gangliosidosis, there is a risk of impairment in executive functioning and memory as well as cerebellar dysfunction. Dementia was not present in any subjects in the current sample.

Adolescent↗

Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia.

OBJECTIVE: To define the behavioral profile of periventricular nodular heterotopia (PNH), a malformation of cortical development that is associated with seizures but reportedly normal intelligence, and to correlate the results with anatomic and clinical features of this disorder. METHODS: Ten consecutive subjects with PNH, all with epilepsy and at least two periventricular nodules, were studied with structural MRI and neuropsychological testing. Behavioral results were statistically analyzed for correlation with other features of PNH. RESULTS: Eight of 10 subjects had deficits in reading skills despite normal intelligence. Processing speed and executive function were also impaired in some subjects. More marked reading difficulties were seen in subjects with more widely distributed heterotopia. There was no correlation between reading skills and epilepsy severity or antiepileptic medication use. CONCLUSION: The neuronal migration disorder of periventricular nodular heterotopia is associated with an impairment in reading skills despite the presence of normal intelligence.

Adolescent↗

Serum inflammatory proteins and cognitive decline in older persons.

OBJECTIVE: To assess whether serum levels of the inflammatory proteins alpha(1)-antichymotrypsin (ACT), C-reactive protein (CRP), interleukin-6 (IL-6), and albumin are associated with cognitive decline in older persons. METHODS: The study sample consisted of 1,284 participants in the Longitudinal Aging Study Amsterdam, aged 62 to 85 years. Cognition was assessed on general cognition (Mini-Mental State Examination [MMSE]), memory (Auditory Verbal Learning Test), fluid intelligence (Raven's Colored Progressive Matrices), and information-processing speed (Coding Task) at baseline and at 3-year follow-up. RESULTS: The highest tertile of ACT was associated with an increased risk of decline on the MMSE (age-, sex-, education-adjusted odds ratio [OR] 1.60; 95% CI: 1.05 to 2.43) but not on any other cognitive test score. CRP, IL-6, and albumin were not associated with cognitive decline on any cognitive test in our study. CONCLUSIONS: This population-based study showed that the serum inflammatory protein alpha1-antichymotrypsin is associated with cognitive decline in older persons, whereas C-reactive protein, interleukin-6, and albumin are not.

Aged↗

Benefits of rivastigmine on attention in dementia associated with Parkinson disease.

In a 24-week, randomized, double-blind, placebo-controlled, multicenter study of rivastigmine, 487 patients with dementia associated with Parkinson disease underwent assessment of attention on the Cognitive Drug Research computerized cognitive assessment system before dosing and 16 and 24 weeks later. Significant benefits of rivastigmine over placebo were seen on all aspects of attention assessed: sustained attention, focused attention, consistence of responding, and central processing speed.

Aged↗

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p <or= 0.01, one domain p <or= 0.05). Blood lead was not associated with any cognitive domain. Associations with tibia lead were attenuated after adjustment for years of education, wealth, and race/ethnicity. CONCLUSIONS: Independent of recent lead dose, retained cumulative dose resulting from previous environmental exposures may have persistent effects on cognitive function. A portion of age-related decrements in cognitive function in this population may be associated with earlier lead exposure.

Age Factors↗

Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis.

Previous research has suggested that cerebral lesions observed on magnetic resonance imaging (MRI) of MS patients are clinically "silent." We examined the validity of this assertion by correlating neuropsychological test performance with MRI findings in 53 MS patients. We used a semiautomated quantitation system to measure three MRI variables: total lesion area (TLA), ventricular-brain ratio (VBR), and size of the corpus callosum (SCC). Stepwise multiple regression analyses indicated that TLA was a robust predictor of cognitive dysfunction, particularly for measures of recent memory, abstract/conceptual reasoning, language, and visuospatial problem solving. SCC predicted test performance on measures on mental processing speed and rapid problem solving, while VBR did not independently predict cognitive test findings. These findings suggest that cerebral lesions in MS produce cognitive dysfunction and that MRI may be a useful predictor of cognitive dysfunction.

Brain↗

Signs of cognitive change in HIV disease: an event-related brain potential study.

We recorded event-related brain potentials (ERPs) from 2 groups of human immunodeficiency virus (HIV)-positive men with no physical illness or neurologic involvement: 9 asymptomatic (AS+) and 9 classified as having either acquired immunodeficiency syndrome (AIDS; 7) or AIDS-related complex (ARC; 2). In separate choice reaction time tasks, the subjects pressed buttons to randomly presented auditory or visual stimuli at probabilities of either 20/80 or 50/50. There were no group differences on any of the neuropsychological tests commonly used in screening batteries for HIV patients. In contrast, reduced P300 amplitudes and increased P300 latencies occurred in ARC/AIDS patients in response to both auditory and visual stimuli, while in AS+ patients such alterations occurred only in the visual modality. Significant delays in P2 latency were found only in the auditory modality and then only in ARC/AIDS patients. ARC/AIDS patients alone showed delayed response times, and only in the auditory modality. The P300 results demonstrate alterations in stimulus evaluation and processing speed in the earliest stages of HIV disease, even before cognitive deficits can be detected by more traditional measures.

AIDS-Related Complex↗