RESUMO
BACKGROUND: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. METHODS: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) and obese (BMI ≥ 30 kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. RESULTS: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). CONCLUSIONS: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.
Assuntos
Diabetes Mellitus , Síndrome de Down , Síndrome Metabólica , Estado Pré-Diabético , Adulto , Pessoa de Meia-Idade , Feminino , Humanos , Masculino , Leptina , Sobrepeso/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Proteína C-Reativa , Adiponectina , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/complicações , Hemoglobinas Glicadas , Estudos Transversais , Síndrome de Down/epidemiologia , Síndrome de Down/complicações , Obesidade/epidemiologia , Obesidade/complicações , Insulina , Índice de Massa Corporal , ColesterolRESUMO
OBJECTIVES: To investigate the relation of plasma levels of Abeta peptides (Abeta1-40 and Abeta1-42) and apolipoprotein E (APOE) genotype to dementia status, and the duration of Alzheimer's disease (AD) in adults with Down syndrome (DS). METHODS: Adults with DS were recruited from community settings and followed up for a mean period of 6.7 years. Plasma levels Abeta1-40 and Abeta1-42 and APOE genotype were determined at the last visit. RESULTS: There were 83 nondemented participants and 44 participants with prevalent AD. Overall, plasma levels of Abeta1-42, Abeta1-40 and the ratio Abeta1-42/Abeta1-40 did not differ significantly between the adults with DS. Among demented participants, the mean level of Abeta1-40 was significantly lower (157.0 vs. 195.3) and the ratio of Abeta1-42/Abeta1-40 was significantly higher (0.28 vs. 0.16) in those with more than 4 years duration of dementia than in those with 4 or fewer years' duration of dementia. This pattern was generally similar in those with and without an APOE epsilon4 allele. CONCLUSIONS: There is an association between plasma Abeta peptide levels and the duration of AD in older persons with DS. The predictive and diagnostic roles of Abeta1-42 and Abeta1-40 measurements for AD, however, remain controversial. Change in Abeta peptide levels with onset of AD and with the duration of dementia may account for a lack of difference between prevalent cases and nondemented individuals and for variation in the predictive power of Abeta peptide levels.
Assuntos
Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/sangue , Síndrome de Down/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Alelos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Biomarcadores/sangue , Estudos de Coortes , Demência/sangue , Demência/diagnóstico , Síndrome de Down/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Valor Preditivo dos Testes , Fatores de TempoRESUMO
OBJECTIVE: Virtually all adults with Down syndrome (DS) have neuropathological manifestations of Dementia in Alzheimer's disease (DAD) but not all develop clinical psychopathology. The effect of allelic variants of Apolipoprotein (APOE) gene in development and progression of DAD and mortality in persons with DS is examined. METHODS: Recruited participants with DS underwent two to 14 sequential assessments over a follow up period of 6 years on average and their APOE genotype determined. Dementia status was confirmed as recommended by the Working Group for the Establishment of Criteria for the Diagnosis of Dementia in Individuals with Intellectual Disability. RESULTS: APOE genotype results were available for 252 individuals. Participants with APOE epsilon 4 allele had significantly higher risk of developing DAD (HR = 1.8, 95% CI: 1.12-2.79), had an earlier onset of DAD (55.0 vs 57.0 years; p = 0.0027) and a more rapid progression to death compared with participants with epsilon 3 allele (4.2 years vs. 5.4 years, respectively, p = 0.048). In non-demented persons with DS, epsilon 4 allele was associated with earlier death by 17 years (mean survival age, 55.7 vs. 72.7 years; HR = 5.9, 95% CI: 1.7-21.3). CONCLUSIONS: This study highlights the relationship of APOE genotype to morbidity and mortality in persons with DS which has important clinical implications. We recommend screening for APOE genotype in persons with DS to identify those at risk of DAD and premature death. Further research is required to investigate the underlying reasons for the early mortality in non-demented DS persons with an epsilon 4 allele.
Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Síndrome de Down/genética , Frequência do Gene/genética , Alelos , Doença de Alzheimer/mortalidade , Progressão da Doença , Síndrome de Down/mortalidade , Feminino , Predisposição Genética para Doença/genética , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Análise de SobrevidaRESUMO
Telomere size (quantified by fluorescence intensity and physical lengths) in short-term T-lymphocyte cultures from adults with Down syndrome (DS) with and without mild cognitive impairment (MCI-DS) or dementia was compared. For these studies, dementia status was determined based on longitudinal assessments employing a battery of cognitive and functional assessments developed to distinguish adult-onset impairment from preexisting developmental disability. In the course of our studies using a MetaSystems Image Analyzer in combination with ISIS software and a Zeiss Axioskop 2, we found that Fluorescein isothiocyanate (FITC) telomere fluorescence referenced to chromosome 2-identified FITC probe fluorescence as a nontelomere standard (telomere/cen2 ratio) showed great promise as a biomarker of early decline associated with Alzheimer's disease (AD) in this high-risk population. We have now obtained a cen (2) CY3 probe that can clearly be distinguished from the blue-green FITC interphase telomere probe, providing a clear distinction between telomere and centromere fluorescence in both interphase and metaphase. We used FITC/CY3 light intensity ratios to compare telomere length in interphases in adults with DS with and without MCI-DS or dementia. Five age-matched female and five age-matched male pairs (n = 10) all showed clear evidence of telomere shortening associated with clinical progression of AD (P < 0.002 - P < 0.000001), with distributions of mean values for cases and controls showing no overlap. We also examined the time needed for microscopy using interphase versus metaphase fluorescence preparations. With interphase preparations, examination time was reduced by an order of magnitude compared with metaphase preparations, indicating that the methods employed herein have considerable practical promise for translation into broad diagnostic practice.
RESUMO
We compared levels of plasma amyloid beta-peptides Abeta1-42 and Abeta1-40 in 108 demented and nondemented adults with Down syndrome (DS) and 64 adults from the general population. Abeta1-42 and Abeta1-40 levels were significantly higher in adults with DS than in controls (P=0.0001). Compared to nondemented adults with DS, Abeta1-42 levels in demented adults with DS were selectively increased by 26% (28.2 pg/ml vs. 22.4 pg/ml, P=0.004). In addition, mean plasma levels of Abeta1-42 were 22% higher in DS cases with the apolipoprotein varepsilon4 allele than in DS subjects without an varepsilon4 allele (25.9 pg/ml vs. 21.2 pg/ml, P=0.01), while mean plasma levels of Abeta1-40 did not vary by APOE genotype. These results support the hypothesis that Abeta1-42 plays an important role in the pathogenesis of dementia associated with DS, as it does in Alzheimer's disease, and that variations in plasma levels may be related to disease progression.
Assuntos
Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/sangue , Síndrome de Down/sangue , Fragmentos de Peptídeos/sangue , Adulto , Alelos , Doença de Alzheimer/genética , Apolipoproteína E4 , Apolipoproteínas E/genética , Progressão da Doença , Síndrome de Down/genética , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Among adults with mental retardation, mortality rates for those with Down syndrome are higher than for those without Down syndrome. We studied age-related changes in functioning and their relation to subsequent mortality in adults with mental retardation. Among people without Down syndrome, recent loss of basic skills was associated with substantially elevated mortality rates. This was not so in the Down syndrome group, however. Adults with Down syndrome tended to experience regression in adaptive behavior earlier than did those without Down syndrome. Incidence rates in the two groups diverged subsequent to age 40. Adults without Down syndrome, however, did also tend to regress when older.
Assuntos
Atividades Cotidianas , Síndrome de Down/mortalidade , Síndrome de Down/fisiopatologia , Adulto , Fatores Etários , Idoso , Apraxias/epidemiologia , California/epidemiologia , Distribuição de Qui-Quadrado , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Incidência , Deficiência Intelectual/etiologia , Deficiência Intelectual/mortalidade , Deficiência Intelectual/fisiopatologia , Funções Verossimilhança , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Demência/epidemiologia , Síndrome de Down/epidemiologia , Adaptação Psicológica , Adulto , Comorbidade , Demência/diagnóstico , Feminino , Humanos , Masculino , PrevalênciaRESUMO
OBJECTIVE: To examine changes in levels of plasma amyloid-ß (Aß) peptides, Aß42 and Aß40, in relation to onset of Alzheimer disease (AD) in adults with Down syndrome (DS). METHODS: Plasma Aß42 and Aß40 were measured at initial examination and at follow-up in a community-based cohort of 225 adults with DS who did not have dementia at baseline and were assessed for cognitive/functional abilities and health status and followed at 14- to 20-month intervals. We used Cox proportional hazards modeling to estimate the cumulative incidence of AD by Aß peptide change group (increasing, no change, or decreasing), adjusting for covariates. RESULTS: Sixty-one (27.1%) of the participants developed AD. At follow-up, a decrease in Aß42 levels, a decrease in the Aß42/Aß40 ratio, and an increase in Aß40 levels were related to conversion to AD. Compared with the group with increasing levels of Aß42, the likelihood of developing AD was 5 times higher for those whose plasma Aß42 levels decreased over follow-up (hazard ratio [HR] = 4.9, 95% confidence interval [CI] 2.1-11.4). Decreasing Aß42/Aß40 was also strongly related to AD risk (HR = 4.9, 95% CI 1.8-13.2), while decreasing Aß40 was associated with lower risk (HR = 0.4, 95% CI 0.2-0.9). CONCLUSIONS: Among adults with DS, decreasing levels of plasma Aß42, a decline in the Aß42/Aß40 ratio, or increasing levels of Aß40 may be sensitive indicators of conversion to AD, possibly reflecting compartmentalization of Aß peptides in the brain.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/sangue , Síndrome de Down/sangue , Síndrome de Down/complicações , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de TempoRESUMO
A statewide survey of New York's community residences for developmentally disabled persons was conducted in which program auspice, history and affiliation, physical structure, community relations, residence staff, and occupant characteristics were examined. The results revealed a diverse system, with certain characteristics similar to those reported in previous national community residence surveys. Principal differences between the statewide data and the national surveys related to residence auspice, size, and staff demographics. These differences are explained as a function of both survey sampling strategies and program differences. Implications of the data are discussed.
Assuntos
Deficiência Intelectual/reabilitação , Instituições Residenciais , Adolescente , Adulto , Fatores Etários , Idoso , Serviços Comunitários de Saúde Mental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York , Fatores SexuaisRESUMO
Adaptive skills of 2,144 individuals with Down syndrome were compared to a similar group of 4,172 developmentally disabled people without Down syndrome. Activities of daily living and cognitive skills were examined across etiology, age group, and level of mental retardation. For individuals with Down syndrome at all levels of retardation, adaptive competence declined with increasing age to a greater extent than for retarded control subjects. Clear age-related deficits associated with Down syndrome were observed only in people older than 50 years of age. Findings support previous evidence of an increased risk for the clinical signs of Alzheimer's disease among people with Down syndrome; however, signs of dementia appeared later in life than would be predicted from available neuropathological data.
Assuntos
Doença de Alzheimer/psicologia , Síndrome de Down/psicologia , Regressão Psicológica , Ajustamento Social , Atividades Cotidianas , Adulto , Idoso , Transtornos Cognitivos/psicologia , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de RiscoRESUMO
We interviewed caregivers and reviewed medical records of 278 adults with mental retardation with and without Down syndrome, 45 to 74 years of age. Standardized morbidity ratios were used to compare frequency of medical disorders in these adults to frequency in the general population. In adults with mental retardation, the frequency of common age-related disorders was comparable to that in the general population, but there was an increased frequency of thyroid disorders, nonischemic heart disorders, and sensory impairment. Surveillance of health status and increased access to health care for screening and treatment of age-related disorders that are more frequent in adults with mental retardation would be important to prevent the development or delay the impact of these conditions and to promote healthy aging.
Assuntos
Doença Crônica/epidemiologia , Nível de Saúde , Deficiência Intelectual/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Deinstitutionalization and the ensuing establishment of residence programs for developmentally disabled persons has stimulated both community support and opposition. The present study considers changes in the levels of community acceptance after residence programs are established, sources of program support and opposition, and strategies used to overcome community opposition. The data are based upon responses to a survey of all community residence programs in New York (n = 459). The findings indicate marked and consistent shifts toward the acceptance of established residence programs.
Assuntos
Relações Comunidade-Instituição , Educação de Pessoa com Deficiência Intelectual , Casas para Recuperação , Adulto , Atitude , Criança , Desinstitucionalização , Deficiências do Desenvolvimento/psicologia , Humanos , New YorkRESUMO
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.