Neurodevelopmental outcomes in children after the fontan operation.
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BACKGROUND: Previous studies of patients after the Fontan operation have reported IQ scores lower than population norms. In the past decade, changes have occurred both in surgical methods used and in the patient population undergoing Fontan palliation. The present study examined the impact of these changes on neurodevelopmental outcomes after Fontan. METHODS AND RESULTS: Neuropsychological tests were administered to 27 five-year-old children after Fontan. Mean age at repair was 2 years 4 months. The present sample was compared with an earlier Fontan group (EFG) of 133 patients who underwent surgery in the 1970s and 1980s. Mean age at repair for the EFG was 7 years 3 months. Compared with EFG, the present study sample was younger at Fontan (P=0.0001) and more likely to have undergone a Norwood procedure (P=0.02), a pre-Fontan bidirectional cavopulmonary anastomosis (P<0.001), and Fontan fenestration (P=0.001). Although mean full-scale, verbal, and performance IQ scores were within 1 SD (15 points) of the population mean of 100 (93+/-16, 95+/-15, and 91+/-17, respectively), mean full-scale and performance IQ scores were significantly lower than this population mean (P=0.03 and P=0.01, respectively). CONCLUSIONS: Compared with a historical cohort of Fontan patients from this institution, a staged approach to Fontan earlier in life is not detrimental to neurodevelopmental outcome. Neurodevelopmental outcomes in children after Fontan are in the normal range, but performance remains lower than the general population. (+info)
beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.
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Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated. (+info)
Are antipsychotic drugs the right treatment for challenging behaviour in learning disability?: The place of a randomised trial.
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People with learning disability sometimes display challenging behaviour. This can be managed by use of antipsychotic medication or behavioural therapy or both. There is no solid evidence, however, that these therapies are safe and effective. A randomised controlled trial of antipsychotic medication has been proposed to deliver such evidence. However, this presents difficult issues in the ethics of research with learning disabled people. In particular, is a trial the most efficient and fairest way to evaluate practice in this area? This paper reviews the clinical situation, gives the rationale for the trial, and analyses the ethical arguments for and against such a trial. (+info)
Spatial learning deficits in amyloid precursor protein 770 transgenic mice.
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OBJECTIVE: To determine whether learning deficits could be seen in transgenic mice expressing human amyloid precursor protein 770 (APP770). METHODS: Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group. All mice were subjected to various behavioral tasks including the Y-maze task and the Morris water maze. After behavioral testing, the mice were sacrificed, and their brain tissues were used for measuring the choline acetyltransferase (ChAT) activity. RESULTS: Nine-month-old transgenic mice exhibited spatial learning deficits in the Morris water maze and in spontaneous alternation in the Y-maze, compared with those of the age-matched non-transgenic mice. The behavioral changes accompanied a reduction of ChAT activity in the cortical and hippocampal regions of transgenic mice. On the other hand, these behavioral deficits were not observed in transgenic mice either at 3 or at 6 months of age, in which ChAT activity remained unchanged. CONCLUSIONS: The present results show that the learning impairment observed in 9-month-old APP770 transgenic mice are accompanied by a decrease in cortical and hippocampal ChAT activities. This suggests that cholinergic deficits may be involved in the learning impairment observed in these APP770 mice. This model will be a useful tool in advancing our understanding of the relationship between the cholinergic system and the cognitive deficits observed in Alzheimer's disease (AD). (+info)
Birth weight and school-age disabilities: a population-based study.
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Mortality rates have declined for low birth weight and extremely low birth weight infants. Yet, the consequences of survival for these children may be adverse developmental outcomes. Few studies to date have examined school-age outcomes for these children. The participants in this study represented a population-based cohort of Florida children who were born between 1982 and 1984 and who were receiving a public school education in 1996-1997. Linkage methodology was used to establish a cohort of 267,213 children aged 12-15 years with both birth certificate and school records. Birth weights were stratified into 500-g increments beginning with +info)
Motivation and learning styles in young children with Down syndrome.
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There are both psychological and biological reasons to expect that certain areas of learning will present young children with Down syndrome with significant problems. Knowledge of the neurological underpinnings of these specific difficulties can often allow compensatory teaching strategies to be put in place, however, and some of these have proved highly effective. The impact of the psychological environment on the progress of development in children with Down syndrome is less well understood. Experience of how others respond to their attempts at understanding the physical and social world and the balance of successes and failures they experience in their early learning are both likely to influence the approach to learning adopted when faced with mastering new skills. Findings from inter-linking studies of cognitive and socio-cognitive development which have explored learning behaviours at different ages and at different developmental stages illustrate how a learning style can sometimes evolve over time in which less than efficient use is made of current levels of cognitive ability. Social ploys are sometimes used to avoid engagement in learning, with the net effect that opportunities to learn new skills are not fully exploited and old skills are sometimes inadequately consolidated. Findings of a misuse of social skills in cognitive contexts do not necessarily provide support for the widely-held view that social understanding is an area of strength in children with Down syndrome and less vulnerable to disruption than cognitive development. Data from a recent study of face-processing abilities suggest that there may in fact be a specific weakness in a fundamental skill normally underpinning the development of social understanding: the ability to recognise differences in emotional expressions. The children with Down syndrome in this study had few problems in correctly identifying individual faces but evidenced difficulties in reliably interpreting the emotional expressions portrayed in these faces. These findings are consistent with the emerging picture of neurological disruption in Down syndrome and with what is known of the neurology underlying this key component in social cognition. As most learning takes place in a social context, the findings have implications for adult-child and child-child learning partnerships and would seem to merit further investigation. (+info)
Mice deleted for the DiGeorge/velocardiofacial syndrome region show abnormal sensorimotor gating and learning and memory impairments.
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Del22q11 syndrome is caused by heterozygous deletion of an approximately 3 Mb segment of chromosome 22q11.2. Children diagnosed with del22q11 syndrome commonly have learning difficulties, deficits of motor development, cognitive defects and attention deficit disorder. They also have a higher than normal risk for developing psychiatric disorders, mainly schizophrenia, schizoaffective disorder and bipolar disorder. Here, we show that mice that are heterozygously deleted for a subset of the genes that are deleted in patients have deficits in sensorimotor gating and learning and memory. The finding of sensorimotor gating deficits is particularly significant because patients with schizophrenia and schizotypal personality disorder show similar deficits. Thus, our deletion mouse models at least two major features of the del22q11-associated behavioral phenotype, and as such, represents an animal model of this complex behavioral phenotype. These findings not only open the way to pharmacological analyses that may lead to improved treatments, but also to the identification of gene/s that modulate these specific behaviors in humans. (+info)
Long-term affective disorder in people with mild learning disability.
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BACKGROUND: Increased risk of affective disorder in learning disability has been reported, although the extent to which this is due to adverse social and material circumstances is uncertain and there have been potential limitations in the measurement of affective disorder. AIMS: To determine risk of affective disorder in those classified with mild learning disability in the British 1946 birth cohort and to investigate whether this risk was accounted for by disadvantage in childhood and adulthood. METHOD: Learning disability was defined as the equivalent of an IQ < or =69 at age 15 years. The Present State Examination at age 36 years and the Psychiatric Symptom Frequency Scale at age 43 years provided psychiatric outcome measures. RESULTS: Learning disability was associated with a fourfold increase in risk of affective disorder, not accounted for by social and material disadvantage or by medical disorder. CONCLUSIONS: Learning disability is strongly associated with risk of affective disorder, persisting well into midlife. (+info)