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Brain metabolites and cognitive function among older depressed and healthy individuals using 2D MR spectroscopy.

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Two-dimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

Age Factors↗

Preliminary validity of "integneuro": a new computerized battery of neurocognitive tests.

The purpose of this study was to examine the preliminary validity of a newly developed battery of computerized cognitive measures, IntegNeuro. This standardized and semi-automated computerized battery assesses sensori-motor function, attention, new learning and memory, language fluency, executive function, and estimated intelligence. A total of 50 healthy individuals (aged 22-80 years) were included in the study. Correlational analyses revealed highly significant associations between the two cognitive batteries. These results support the use of IntegNeuro as a computerized cognitive system. Additional studies are needed to examine the clinical utility of the battery.

Adult↗

Specifying executive representations and processes in number generation tasks.

The Interacting Cognitive Subsystems framework, ICS (Barnard, 1985) proposes that central executive phenomena can be accounted for by two autonomous subsystems, which process different forms of meaning: propositional and schematic (implicational) meanings. The apparent supervisory role of the executive arises from limitations on the exchange of information between these and other cognitive subsystems. This general proposal is elaborated in four experiments in which a total of 1,293 participants are asked to spontaneously generate a large verbal number to varying task constraints, with the intention of specifying the representations of number and task that underlie responses. Responses change systematically according to participants' use of explicit propositional information provided by the instructions, and inferred implicational information about what the experimenter is requesting. There was a high error rate (between 6% and 24%), participants producing responses that did not fall within the large range indicated by the instructions. The studies support the distinction between propositional and implicational processing in executive function, and provide a framework for understanding normal executive representations and processes.

Cognition↗

Neuropsychological disturbances and cerebral blood flow in bipolar disorder.

OBJECTIVE: To determine and correlate alterations in neuropsychological function and cerebral blood flow in bipolar patients. METHOD: Assessments included the Positive and Negative Symptom Scale, Global Assessment Functioning, Wechsler Adult Intelligence Scale (WAIS), Wisconsin Card Sorting Test (WCST), Stroop test, Trail Making Test (TMT), California Verbal Learning Test (CVLT), Wechsler Memory Scale (WMS) and phonetic verbal fluency/controlled oral word association tests. Single photon emission computed tomography (SPECT) was carried out with the administration of 99mTc-HMPAO. Forty-three outpatients out of 85 fulfilling RDC diagnostic criteria for bipolar disorder and six healthy subjects were included in the study. SPECT and neuropsychological assessments were performed in 30 patients in manic (n = 7), hypomanic (n = 8), depressed (n = 12) or euthymic (n = 3) states. All assessments were carried out before starting treatment. RESULT: Several corrected correlations between neuropsychological function and cerebral blood flow (CBF) were identified: executive function (WCST) and striatal, frontal, temporal, cerebellum, parietal and cingulate CBF; memory (WMS, WAIS-Digits) and striatal, frontal, temporal and parietal CBF; attentional tasks (Stroop) and striatal, temporo-medial and parietal CBF; verbal learning (CVLT) and frontal, posterior temporal, cingulate and occipital CBF; psychomotor disturbances (TMT) and anterior temporal CBF; poorer intelligence performance scores (WAIS-Vocabulary) and cerebellum and parietal CBF. CONCLUSIONS: This study confirms the presence of functional disturbances in fronto-subcortical structures, the cerebellum and limbic system in bipolar patients.

Adult↗

Neurodevelopmental outcomes of infants born prematurely.

Long-term follow-up of infants born prematurely is necessary to determine neurodevelopmental outcomes, particularly with the expansion of interest from major disabilities to high prevalence/low severity dysfunctions. Models of pathogenesis include changes due to developmental disruptions and to injury, the magnitude and type of change influenced by the infant's age, and central nervous system recovery and reorganization. Alterations in neurogenesis, migration, myelination, cell death, and synaptogenesis occur even in the absence of insult. Despite increased knowledge regarding these processes, the functional significance of brain abnormalities is unclear. Because of methodologic problems in follow-up studies, it is difficult to characterize outcome definitively. Nonetheless, an acceptable degree of agreement across studies is found with regard to specific neurodevelopmental outcomes: motor/neurologic function, visuomotor integrative skills, IQ, academic achievement, language, executive function, and attention-deficit hyperactivity disorder/behavioral issues. In general, children born prematurely have more problems in these areas than do their normal birth weight counterparts. Suggestions for improved analyses and clarification of outcomes include use of cluster analysis, structural equation modeling, growth curve analysis, developmental epidemiologic approaches, and better control of background variables using risk indexes and factor scores. Better assessment techniques measuring functions documented to be at higher risk of problems are discussed.

Brain Diseases↗

Health related quality of life in adults with repaired tetralogy of Fallot: psychosocial and cognitive outcomes.

OBJECTIVE: To assess the health related quality of life of patients who were operated on during childhood for total correction of tetralogy of Fallot, focusing on the psychosocial and cognitive outcomes. PATIENTS: 54 patients (24 men and 30 women, mean (SD) age 32 (4) years), operated on for total correction of tetralogy of Fallot at mean age of 8.2 years, underwent a cardiological examination, psychological assessment (semistructured interview, Minnesota multiphasic personality inventory), evaluation of quality of life (36 item short form health survey), and neuropsychological assessment with an extensive neuropsychological battery of tests. RESULTS: Psychological characteristics-(1) a lower than normal academic level, (2) a job inadequate for educational level, (3) a preference for an overprotective familiar setting, and (4) a difficulty communicating own corporal image. Denial of the cardiopathy was found to be a common behaviour to normalise functioning. Very few patients had a deficit in memory, learning, or attention functions; rather, patients had a deficit in the executive functions, problem solving, and planning strategies. CONCLUSIONS: Despite a satisfactory health related quality of life, there are residual psychological and social problems in addition to impaired cognitive outcomes in the presence of a normal intelligence quotient.

Adult↗

Relationship between cognition and work functioning among patients with schizophrenia in an urban area of India.

OBJECTIVE: Employment rates and work functioning are poor among patients with schizophrenia and are related to cognitive dysfunction. This study examined the relationship between work functioning and cognition, other clinical and demographic variables, and measures of social functioning among patients with schizophrenia in an urban area of India. METHODS: This study evaluated cognitive dysfunction and work functioning among 88 patients with chronic schizophrenia. Attention, executive function, and memory were tested with a battery of neuropsychological tests. Work and social functions were evaluated with standardized instruments. RESULTS: Fifty-nine patients (67 percent) were employed, most in a mainstream environment. Moderate to significant work dysfunction was present among 21 patients (24 percent). When multivariate analysis was performed, cognitive deficits did not relate significantly to current employment status or to level of performance at work. Negative symptoms predicted employment status, and poor social functioning predicted poor work performance. CONCLUSIONS: The relationship between work and cognitive status in schizophrenia was not as strong as has been previously reported in this population. It was speculated that social factors, such as the compelling need to be employed, a supportive work environment, and the number of years of formal education, were factors underlying the high level of work functioning in this group despite cognitive deficits.

Adult↗

Neuropsychiatric manifestations of multiple sclerosis.

Multiple sclerosis is one of the most frequently observed neurological causes of progressive disability in early to middle adulthood. The disease is variable in its presentation and course, affects roughly 100 to 300 per 100,000 persons within the US alone and is slightly more common among females than males. Multiple sclerosis places substantial burdens on patients, families and caregivers. Its presentation includes disturbances in cognitive abilities and psychiatric functioning, as well as motor difficulties. This article reviews the current literature on the neuropsychiatric manifestations of multiple sclerosis. Cognitive domains discussed include general cognitive functioning, learning and memory ability, attention, processing speed, executive functioning, visual perceptual ability and language functioning. Attention is also given to alterations in neuropsychiatric functioning associated with disease progression and across various disease subtypes. In addition, reports are also reviewed regarding various psychiatric disturbances, affective changes, quality of life issues and fatigue and pain in individuals with multiple sclerosis. Finally, factors pertaining to pediatric populations in multiple sclerosis are addressed.

Attention↗

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↗

The nature of subjective cognitive complaints of older adults.

The current study investigated the nature of subjective cognitive complaints of older adults in relation to a broad array of individual cognitive functions known to decline with age. A 60-item questionnaire was developed to examine: (1) whether older adults experience problems with these cognitive functions (problems with cognition); (2) the extent to which these problems have changed over time (changes in cognition); and (3) whether these cognitive decrements interfere with their daily functioning (difficulties with cognition). The cognitive functions examined were attention, processing speed, working memory, executive function, and memory. One hundred eight-two community-dwelling adults (aged 65-92 years) completed the questionnaire. While participants reported problems with, and changes in, each cognitive function, working memory was recorded as most problematic and demonstrated the most change. Yet, although older adults experience problems with cognition and report changes in cognitive functioning over time, these did not necessarily produce difficulties in daily life. This points to the existence of support mechanisms that may assist older adults in cognitively demanding situations.

Adult↗

[Neuropsychological deficits in hydrocephalus associated spina bifida].

INTRODUCTION. The term spina bifida is used to describe a large number of abnormalities in which the common denominator is incomplete posterior fusion of the vertebral arches. DEVELOPMENT. Spina bifida, as a congenital alteration affecting closure of the neural tube frequently appears in relation to hydrocephaly. The object of this article is to review the neuropsychological alterations which occur in hydrocephaly, with special reference to hydrocephaly linked to spina bifida. The authors suggest consideration of these alterations in view of the new models of cognitive neuropsychology. The commonest alterations are those affecting visual-perceptive and visual-constructive function, working memory, pragmatic use of language and executive functions.

Humans↗

Human brain language areas identified by functional magnetic resonance imaging.

Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact human brain. Language was defined broadly to include both phonological and lexical-semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Functional maps of the entire brain were obtained from 30 right-handed subjects. These maps were averaged in standard stereotaxic space to produce a robust "average activation map" that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal lobes. Less consistent with classical models were (1) the existence of left hemisphere temporoparietal language areas outside the traditional "Wernicke area," namely, in the middle temporal, inferior temporal, fusiform, and angular gyri; (2) extensive left prefrontal language areas outside the classical "Broca area"; and (3) clear participation of these left frontal areas in a task emphasizing "receptive" language functions. Although partly in conflict with the classical model of language localization, these findings are generally compatible with reported lesion data and provide additional support for ongoing efforts to refine and extend the classical model.

Adolescent↗

Cognitive impairment in schizophrenia: its impact on social functioning.

OBJECTIVE: To examine cognitive impairment in schizophrenia and its impact on social functioning. METHOD: Cohort studies recording cognitive and social development, studies of predictors of poor community outcome, and evidence from brain imaging studies are reviewed. RESULTS: Executive function deficits, and poor performance in verbal memory, vigilance, and working memory tests are strong predictors of poor community outcome and impairment in skills learning. PET scans of regional cerebral blood flow suggest a dynamic imbalance between different cerebral areas rather than overall loss of brain function. CONCLUSION: Chronic cognitive impairment is the strongest predictor of social disability. Results suggest that the impairment of brain function associated with executive deficits is not necessarily irreversible and may therefore be treatable with appropriate drug therapy.

Brain↗

Neuropsychological function in adults with attention-deficit hyperactivity disorder.

BACKGROUND: Recent studies indicate that attention-deficit hyperactivity disorder (ADHD) persists into adulthood, but little is known about the neuropsychological features of adult ADHD. Our objective was to assess neuropsychological functioning in adults with ADHD with a battery of executive function tests. METHODS: Subjects were 64 unmedicated adults, 19-59 years of age, with DSM-III-R ADHD of childhood onset who met criteria for ADHD when referred in adulthood and 73 non-ADHD controls of similar age and gender. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Compared with controls, adults with ADHD were significantly impaired on measures of vigilance, semantic encoding for verbal memory, and written arithmetic, irrespective of age, gender, psychiatric comorbidity, or presence of learning disability. Despite comparable educational level and IQ, ADHD adults had a trend to lower occupational attainment and had significantly more academic problems in school. CONCLUSIONS: These executive, attention, and achievement dysfunctions demonstrated in adults with ADHD provide additional support for the validity of the syndrome in adults.

Adult↗

Long-term effects of bilateral frontal brain lesion: 60 years after injury with an iron bar.

BACKGROUND: Harlow's report of the case of Phineas P. Gage in 1848 was one of the earliest description of the personality and behavioral changes following frontal lobe damage. Since Harlow's articles, a few more case reports of frontal lobe damage have been published. As standard neuropsychological and neurologic evaluations may reveal subtle defects, case reports have been particularly useful in characterizing the behavioral changes that follow frontal lobe damage. OBJECTIVE: To describe the long-term outcome of an 81-year-old patient who sustained a severe frontal brain lesion 60 years ago caused by the passage of an iron spike through his head. RESULTS: The patient has bilateral damage affecting the orbital and dorsolateral frontal regions. He displays many of the typical frontal behavioral disturbances described in the literature. His conduct is characterized by dependence on others, cheerfulness, planning difficulties, problems establishing realistic goals, lack of drive, and difficulties in initiating, continuing, and finishing activities. Although gross cognitive functioning is intact, neuropsychological deficits are present in the executive functioning, memory, and visuoconstructive domains. CONCLUSIONS: In contrast with the antisocial conduct pattern usually associated with frontal damage in the literature, this case suggests that large frontal lesions can produce behavioral and personality changes that are compatible with stable functioning in family, professional, and social settings. In addition to the localization of the lesion, many other factors should be considered in the long-term prognosis of frontal brain injured patients.

Adult↗

Cognitive outcomes after deep brain stimulation for Parkinson's disease: a review of initial studies and recommendations for future research.

Modern ablative surgery for movement disorders probably results in less frequent and severe cognitive morbidity than seen in early surgical series. Nonetheless, recent studies indicate that neurobehavioral functions commonly compromised in Parkinson's disease (PD) (e.g., executive functions, verbal fluency, and memory) are negatively impacted in some patients by lesion placement. The potential reversibility of cognitive dysfunction after chronic electrical deep brain stimulation (DBS) for PD has lead some to favor this treatment modality over ablation. This paper reviews the initial studies of the cognitive effects of thalamic, pallidal, and subthalamic DBS. These studies suggest that DBS is relatively safe from a cognitive standpoint and that the benefits of motor improvements probably outweigh the cost of minimal cognitive morbidity. This conclusion must be offered with caution, however, given the small numbers of studies to date and their methodological limitations. Neurobehavioral research has yet to adequately address (1) outcome relative to appropriate control groups; (2) effects of electrode placement versus stimulation; (3) laterality- and site-specific effects of DBS; (4) long-term effects of DBS; (5) effects of stimulation parameters; (6) risk factors for cognitive dysfunction with DBS; (7) whether cognitive dysfunction associated with DBS is reversible; and (8) comparative neurobehavioral outcome after DBS and ablation. DBS affords an exciting opportunity to clarify the neurobehavioral role of the basal ganglia.

Brain↗

No evidence for cognitive side effects after 6 months of vagus nerve stimulation in epilepsy patients.

Vagus nerve stimulation (VNS) can reduce seizure frequency in epilepsy patients and may affect central mechanisms of brain functioning. Experimental studies have provided evidence of cognitive alterations during VNS on phases. This single-arm follow-up study evaluates the potential of VNS to affect cognitive performance following long-term treatment. Thirty-six adult patients with medication-resistant epilepsies enrolled. Cognition was assessed before and at least 6 months after implantation of the stimulation device by a comprehensive neuropsychological assessment battery comprising tests on attention, motor functioning, short-term memory, learning and memory, and executive functions. Neither multiple testing of single score changes nor multivariate testing of cognitive domains revealed significant pre-post changes. Improvements in attentional performance were completely explained by practice effects as is usually expected. In particular, no negative side effects were revealed. These findings are in line with the clinical impression that VNS does not affect cognitive performance.

Journal Article↗

Rey-Osterrieth complex figure: normative values in an Italian population sample.

The Rey-Osterrieth complex figure test (ROCF) is a neuropsychological test extensively used in clinical practice to investigate visuospatial constructional functions, visuographic memory and some aspects of planning and executive function. The aim of the present study was to collect normative values in an Italian normal population sample (n=280) for the direct copying and delayed (10 min) reproduction of the ROCF. Multiple regression analysis revealed significant effects of age and education on performance of both copying tasks, whereas sex appeared to affect only performance on the delayed copying task. Inferential cut-offs have been determined and equivalent scores computed. The availability of equivalent scores for the ROCF will prove useful in clinical assessment since it allows the comparison of a subject's performance on the ROCF with that on other neuropsychological tests for which normative values collected with similar methods are already available for the Italian population.

Adult↗