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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postmortem studies of brains from adults with Down's syndrome (DS) reveal a dramatic age-dependent increase in the incidence of neuropathology associated with Alzheimer's disease (AD). By the age of 40 years, virtually all DS individuals have AD neuropathology. Documentation of cognitive correlates of this phenomenon has been difficult, partly because of the preexisting mental retardation in DS. In the current study, we compared a group of adults with DS, 22 to 51 years old, with a matched control group on various behavioral measures such as savings scores, which are known to be sensitive in detecting early dementia in AD patients. By using the short delayed savings score from the California Verbal Learning Test (a test of verbal memory), a subgroup of DS adults was identified as memory-impaired. This group demonstrated a decline in performance on various other cognitive tests with advancing age, whereas another group identified as having non-memory-impaired DS, and the non-DS controls, showed no evidence of decline with age. These results provide evidence for the presence of early dementia among adults with DS within an age range in which neuropathologic manifestations of AD are predicted to be developing.
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PMID:Cognitive impairment in adults with Down's syndrome: similarities to early cognitive changes in Alzheimer's disease. 830 64

The densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed quantitatively in the brains of 303 mentally retarded adults 23 to 90 years of age at the time of their deaths (mean = 59.5 years). Cases with Down's syndrome, hydrocephalus and metabolic disorders were excluded from the study. Examinations of frontal, temporal, parietal, and occipital cortex, as well as hippocampus and parahippocampal gyrus were made in every case. NPs and/or NFTs were observed within the brains of 163 cases (53.8%). Detailed analyses indicated that NP density within all brain regions examined was positively related to age, with the largest age associated increases in density seen in frontal and temporal regions. In contrast, NFT density increased with age only within hippocampus and parahippocampal gyrus, but not neocortex. In addition, NP lesions within neocortex were more diffusely distributed across regions for older compared to younger cases, while no similar age-associated change in the topography of NFTs was observed. Finally, factor analyses of the combined NP and NFT data indicated that, while strong correlations existed across the various brain regions for measures of NP and NFT densities, considered separately, there was virtually no indication of regional associations between these two types of lesions. While these data, from cases with mental retardation, cannot be generalized directly to the nonretarded population, they provide strong evidence that models of Alzheimer pathogenesis must take into account the fact that regional densities of NPs and NFTs, and, therefore, the underlying processes associated with formation of these lesions, can be largely independent.
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PMID:Alzheimer neuropathology in mentally retarded adults: statistical independence of regional amyloid plaque and neurofibrillary tangle densities. 846 May 32

Down syndrome remains one of the most common causes of mental retardation. Although knowledge of pathogenesis remains incomplete, recent molecular biologic techniques have identified regions of the 21st chromosome critical for expression of the Down syndrome phenotype, and animal models have helped elucidate the origins of the neurochemical and neuropathologic abnormalities. There also has been an improved understanding of the spectrum of medical complications of this disorder and the need for anticipatory management, including the search for atlantoaxial subluxation and hypothyroidism. With its increased risk of Alzheimer disease, Down syndrome is proving to be a useful model for studying aging. Accompanying greater knowledge has been improved functional outcome. Better medical care has made individuals with Down syndrome healthier; remaining at home through childhood has increased their cognitive function; and availability of increased numbers of group homes and supported employment opportunities has permitted the young adult with Down syndrome to live a more independent and full life. In this climate, the role of the pediatrician in early intervention and anticipatory guidance cannot be overemphasized.
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PMID:Down syndrome. 849 63

Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation. Development of the DS brain is associated with decreased neuronal number and abnormal neuronal differentiation, and adults with DS develop Alzheimer's disease. The cause of the neurodegenerative process in DS is unknown. Here we report that cortical neurons from fetal DS and age-matched normal brain differentiate normally in culture, but DS neurons subsequently degenerate and undergo apoptosis whereas normal neurons remain viable. Degeneration of DS neurons is prevented by treatment with free-radical scavengers or catalase. Furthermore, DS neurons exhibit a three- to fourfold increase in intracellular reactive oxygen species and elevated levels of lipid peroxidation that precede neuronal death. These results suggest that DS neurons have a defect in the metabolism of reactive oxygen species that causes neuronal apoptosis. This defect may contribute to mental retardation early in life and predispose to Alzheimer's disease in adults.
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PMID:Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. 852 10

The reliability of psychiatric diagnosis has a direct effect on the validity of post-mortem analyses of neuropathological data, yet little is known about the reliability of retrospective diagnostic procedures which rely on review of medical records. In this paper, we report on the reliability of DSM-III-R psychiatric diagnoses assigned by a pool of 8 raters to a set of 106 state hospital charts of elderly, chronic patients who had died while institutionalized and were autopsied. Diagnoses were grouped by general diagnostic class, and Kappa coefficients computed for agreement among raters, as well as for agreement between ultimate consensus diagnoses and those made while subjects were living. Interrater agreement for those diagnoses that occurred most frequently in this sample (e.g. Schizophrenia and Dementia) was excellent, and comparable to the the agreement observed for ratings of live patients. Interrater agreement for less frequently occurring diagnoses (e.g. Mental Retardation, Mood Disorders, other non-Schizophrenic Psychoses) ranged from excellent to poor. We found high agreement between our rates diagnoses and those assigned by state hospital personnel while patients were living, although post-mortem review produced lower rates of diagnosis of both schizophrenia and Alzheimer-type dementias. Overall, results suggest that the reliability of chart review diagnosis is comparable to that obtained from interviews of live patients when experienced raters are used and diagnostic base rates are high enough to produce stable estimates of reliability.
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PMID:Reliability of post-mortem chart diagnoses of schizophrenia and dementia. 856 97

Through deinstitutionalization, more adults with mental retardation are living in the community under the care of family physicians. Patients with Down syndrome are at high risk for early Alzheimer's disease. This case report describes a 43-year-old woman with Down syndrome whose progressive functional decline over 3 years was attributed to dementia of the Alzheimer type.
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PMID:Dementia and Down syndrome. 865 74

Declines in adaptive behavior were examined in a study of dementia in adults with Down syndrome and other forms of mental retardation. No significant differences were found between adults under 50 years of age with and without Down syndrome. In contrast, individuals over 50 who had Down syndrome were more likely to be classified as having dementia over a range of quantitative decision criteria; nevertheless, prevalence estimates of dementia were substantially below the presumed 100% prevalence of neuropathological markers of Alzheimer disease. This apparent discrepancy between functional and neuropathological findings may be associated with variations in risk associated with Down syndrome genotypes and/or a true lack of correspondence between classical neuropathological hallmarks of Alzheimer disease in this population and clinical expression.
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PMID:Prevalence of dementia in adults with and without Down syndrome. 871 94

We report on the clinical and cytogenetic assessment of five cases of Down syndrome phenotype with either a partial duplication of chromosome 21 or a normal karyotype, and we quote a case of del (21q) syndrome. Down syndromes with a partial duplication of chromosome 21 (as well as cases of del (21q), which are partly the phenotypic countertype of trisomy 21) are of paramount importance in the understanding of genes involved in the phenotype of Down syndrome. The goal is to find the relevant genes implicated in the main traits of Down syndrome (i.e. mental retardation, Alzheimer disease, and serious visceral malformations). Such a goal, in our opinion, cannot be reached just by publishing the genotype and the phenotype of a small cohort of patients: 1. a sufficient number of accurate cases is needed, and 2. data have to be computerized for definite conclusions to be reached. The main aims of this report are to present our study protocol and to invite colleagues to participate in a collaborative study in order to collect a maximum of these (rare) cases.
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PMID:Down syndrome with partial duplication and del (21) syndrome: study protocol and call for collaboration. Study I: Clinical assessment. 872 67

The ubiquitous presence of the neuropathology of Alzheimer disease (AD) in individuals with Down's syndrome (DS) over 40 years of age suggests that this group of people will exhibit a high prevalence of dementia of the Alzheimer type (DAT) as they age. The present study indicates that there is a clear discrepancy between the presumed presence of AD neuropathology and the clinical expression of DAT among older people with DS. In the first 6 years of a longitudinal study, the present authors compared 91 adults (31-63 years of age) with DS and mild or moderate mental retardation to 64 adults (31-76 years of age) with other forms of mental retardation (MR) on yearly measures of mental status, short- and long-term memory, speeded psychomotor function, and visuospatial organization. The results indicated that, over repeated testing on the verbal long-term memory test, younger participants with DS showed small increases in their scores, while older participants with DS showed very slight decreases. Overall performance scores on this test and a speeded psychomotor task were poorer for both diagnostic groups in individuals aged 50 years and older. The magnitude and type of these selective changes in performance were consistent with performance profiles observed in older healthy adults without mental retardation on tests measuring similar cognitive functions. Only four out of the 91 people with DS in the present sample showed changes in functioning that have led to a diagnosis of possible DAT, and in these individuals, alternative causes of performance declines were concurrently present (e.g. thyroid dysfunction). These findings indicate that some age-associated changes in functioning are related to "normal' but probably precocious ageing among adults with DS. Furthermore, these findings suggest that adults with DS and mild or moderate mental retardation may be at lower risk for dementia during their fourth and fifth decades of life than previous studies have suggested.
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PMID:Normal ageing in adults with Down's syndrome: a longitudinal study. 880 62

Down's syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of chromosome 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain, where the occurrence of Alzheimer's disease is observed in trisomy 21 patients over the age of 35. Copper-zinc superoxide dismutase (CuZnSOD) is one of the proteins encoded by chromosome 21 (21q22.1). As a consequence of gene dosage excess, CuZnSOD activity is increased by 50% in all DS tissues. This work reports the SOD activity of a population of DS patients with complete trisomy 21, partial trisomy 21, translocations and mosaicism, in order to confirm the gene dosage effect of SOD on the clinical features of DS, and to help to establish which is the critical region of chromosome 21 in DS. CuZnSOD was measured in red blood cells using the Minami and Yoshikawa method. In the population with complete trisomy 21, SOD activity was increased by 42%; in the population with partial trisomy 21, translocations and mosaicism, SOD activity was normal. In the population diagnosed as DS, but not karyotyped, SOD activity was increased by 28%. No differences between sexes or among ages were found. We conclude that the 21q22.1 segment is not the critical region responsible for DS, as we have found normal SOD activity in patients with the clinical features of DS.
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PMID:Overexpression of copper-zinc superoxide dismutase in trisomy 21. 884 14


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