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Developmental Neurobiology Jul 2019The present study provided an investigation of associations between leisure activity and early Alzheimer's disease neuropathology (i.e., brain β-amyloid) and episodic...
The present study provided an investigation of associations between leisure activity and early Alzheimer's disease neuropathology (i.e., brain β-amyloid) and episodic memory in a sample of 65 adults with Down syndrome (aged 30-53 years), at baseline and follow-up, approximately three years apart. Findings indicated that leisure activity at baseline was not associated with brain β-amyloid at baseline or change in brain β-amyloid from baseline to follow-up. Greater cognitively stimulating leisure activity at baseline was associated with better episodic memory at baseline, and greater social leisure activity at baseline was associated with less decline in episodic memory from baseline to follow-up. High (as opposed to low) levels of social and overall leisure activity at baseline moderated the association between increase in brain β-amyloid and decline in episodic memory, from baseline to follow-up. Findings suggest that cognitively stimulating and social leisure activity could protect against the effect of Alzheimer's disease neuropathology on episodic memory in adults with Down syndrome.
Topics: Adult; Amyloid beta-Peptides; Brain; Down Syndrome; Female; Follow-Up Studies; Humans; Leisure Activities; Longitudinal Studies; Male; Memory, Episodic; Middle Aged; Positron-Emission Tomography; Surveys and Questionnaires
PubMed: 30912871
DOI: 10.1002/dneu.22677 -
The International Journal of... Mar 1989The etiopathogenesis of Down syndrome is reviewed concentrating on the possible consequences of over-expression of cytoplasmic superoxide dismutase gene located in... (Review)
Review
The etiopathogenesis of Down syndrome is reviewed concentrating on the possible consequences of over-expression of cytoplasmic superoxide dismutase gene located in chromosome 21. Increased superoxide dismutase activity may generate free radical stress through overproduction of hydrogen peroxide. The significance of inadequate adaptive responses, i.e. increase of the selenoenzyme glutathione peroxidase activity in the central nervous system and in the thyroid gland is discussed. Suggestions are made for prevention of the progress of Down syndrome and intervention studies with antioxidant supplementation are proposed.
Topics: Antioxidants; Cytoplasm; Down Syndrome; Free Radicals; Humans; Superoxide Dismutase
PubMed: 2534992
DOI: No ID Found -
Journal of Neurodevelopmental Disorders Aug 2019Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different...
BACKGROUND
Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community.
RESULTS
Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while five were used in two different studies. Eleven studies reporting AB test data met inclusion for this review, with seven different AB tests used. The only AB scales to be used by more than one study were the Vineland Adaptive Behaviour Scale (VABS; used by three studies) and the Vineland Adaptive Behavior Scale 2nd Edition (VABS-II; used by two studies). A variety of additional factors were identified which make comparison of test scores between studies problematic, including different score types provided between studies (e.g. raw scores compared to age-equivalent scores) and different participant inclusion criteria (e.g. whether individuals with cognitive decline were excluded). Floor effects were common for IQ tests (particularly for standardised test scores). Data exists to suggest that floor effects may be minimised by the use of raw test scores rather than standardised test scores. Raw scores may, therefore, be particularly useful in longitudinal studies to track change in cognitive ability over time.
CONCLUSIONS
Studies assessing general ability in adults with DS are likely to benefit from the use of both IQ and AB scales. The DS research community may benefit from the development of reporting standards for IQ and AB data, and from the sharing of raw study data enabling further in-depth investigation of issues highlighted by this review.
Topics: Adaptation, Psychological; Aptitude; Down Syndrome; Humans; Intelligence; Intelligence Tests
PubMed: 31470792
DOI: 10.1186/s11689-019-9279-8 -
Genetics in Medicine : Official Journal... Nov 2018We systematically reviewed the published literature on test failure rates for the sequencing of cell-free DNA (cfDNA) in maternal plasma to identify Down syndrome.
PURPOSE
We systematically reviewed the published literature on test failure rates for the sequencing of cell-free DNA (cfDNA) in maternal plasma to identify Down syndrome.
METHODS
We searched peer-reviewed English publications with diagnostic results on all pregnancies that provided test failure rates. Data on the odds of failure in Down syndrome and euploid pregnancies and the impact of repeat testing were extracted. Random-effects modeling was then used to identify moderators that could explain variability.
RESULTS
Thirty articles satisfied the inclusion criteria for overall failure rates. Study location (Western and Asian with initial testing, and Western with repeat testing) were significant moderators with failure rates of 3.3, 0.6, and 1.2%, respectively (P = 0.001). The odds ratio for Down syndrome in successful versus failed tests was 0.98 (95% confidence interval: 0.62-1.55, I = 0%). Repeat testing from 14 large clinical cohort studies found that 83% (range: 52-100%) of failures were repeated, with 79% (range: 46-97%) being successful.
CONCLUSION
Lower failure rates in Asian studies may be related to not routinely measuring the fetal fraction and to fewer obese women. Repeat cfDNA testing is effective in providing reliable results after initial failures. Protocols for primary cfDNA screening should focus on Down syndrome, with less common and more structurally abnormal trisomy 18 and 13 pregnancies treated as adjuncts.
Topics: Adult; Cell-Free Nucleic Acids; Down Syndrome; Female; Humans; Maternal Age; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Risk Factors
PubMed: 30514979
DOI: 10.1038/gim.2018.22 -
Nature Reviews. Neurology Mar 2019Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to... (Review)
Review
Virtually all adults with Down syndrome (DS) show the neuropathological changes of Alzheimer disease (AD) by the age of 40 years. This association is partially due to overexpression of amyloid precursor protein, encoded by APP, as a result of the location of this gene on chromosome 21. Amyloid-β accumulates in the brain across the lifespan of people with DS, which provides a unique opportunity to understand the temporal progression of AD and the epigenetic factors that contribute to the age of dementia onset. This age dependency in the development of AD in DS can inform research into the presentation of AD in the general population, in whom a longitudinal perspective of the disease is not often available. Comparison of the risk profiles, biomarker profiles and genetic profiles of adults with DS with those of individuals with AD in the general population can help to determine common and distinct pathways as well as mechanisms underlying increased risk of dementia. This Review evaluates the similarities and differences between the pathological cascades and genetics underpinning DS and AD with the aim of providing a platform for common exploration of these disorders.
Topics: Alzheimer Disease; Down Syndrome; Humans
PubMed: 30733618
DOI: 10.1038/s41582-018-0132-6 -
The British Journal of General Practice... Jan 2007Individuals with Down's syndrome are predisposed to a variety of medical conditions which can impose an additional, but preventable, burden of secondary disability....
BACKGROUND
Individuals with Down's syndrome are predisposed to a variety of medical conditions which can impose an additional, but preventable, burden of secondary disability. Although there are guidelines for health checks and medical management of children with Down's syndrome, the needs of adults are relatively neglected.
AIM
To determine the prevalence of common medical problems in adults with Down's syndrome, and to assess current practice regarding medical surveillance of these patients.
DESIGN OF STUDY
Detailed notes analysis.
SETTING
Data were obtained from the primary care records of adults with Down's syndrome living in the Newcastle upon Tyne and Gateshead areas.
METHOD
Case notes were reviewed to obtain details regarding complications and to determine the frequency of medical surveillance of individuals with Down's syndrome.
RESULTS
Complications such as hypothyroidism, celiac disease, and obesity occur more frequently in adults with Down's syndrome than previous paediatric prevalence studies suggest. Surveillance of common complications that occur in individuals with Down's syndrome is infrequent. In this study, 48% of adults with Down's syndrome had not seen a doctor in the previous 12 months and 33% had not had a medical assessment in the previous 3 years.
CONCLUSION
Many individuals with Down's syndrome do not have access to regular healthcare checks, despite the high frequency of common medical complications in adult life. Debate regarding the practicality and relevance of introducing regular health checks is warranted.
Topics: Adolescent; Adult; Community Health Services; Down Syndrome; England; Female; Genetic Predisposition to Disease; Genetic Testing; Health Services Accessibility; Humans; Male; Middle Aged; Prevalence
PubMed: 17244425
DOI: No ID Found -
International Journal of Environmental... Jan 2021The objective of this study is to assess the evidence about the demographic transformation of the Down Syndrome population, with a specific focus on prenatal testing,...
The objective of this study is to assess the evidence about the demographic transformation of the Down Syndrome population, with a specific focus on prenatal testing, and to identify sources frequently used for demographic assessment of Down Syndrome in the world. We reviewed existing studies on demographic transformations in the population with Down Syndrome, specifically birthrate indicators, under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. The searches were made in Medline (via EBSCO Host), Academic Search Complete (via EBSCO Host), PsycINFO (via EBSCO Host), Web of Science (Core Collection), Public Health Database (via ProQuest), and The Cochrane Library. The terms were developed through Medical Subject Headings (MESH) and American Psycological Asociation Thesaurus of Psychological Index Terms (APA). Full texts were reviewed if information was given regarding location and birthrate for a range of three years or more, and if the first and last year considered was within 1960 and 2019. We found 22 references with a period of study between 1960 and 2019 following the global spread of prenatal testing for Down Syndrome. We found a consistent association between prenatal diagnosis and birthrate, enough to explain the significant fall in the prevalence of Down Syndrome, a somewhat rising incidence of Down Syndrome related to increased maternal age and extension of fertility services in healthcare systems, a generalized use of specific congenital birth defect registries as the primary source of data, and an unclear influence of socio-cultural and territorial variables. Our findings can inform research, policy, and practice to improve the reproductive health and quality of life of the population with Down Syndrome.
Topics: Birth Rate; Demography; Down Syndrome; Female; Humans; Maternal Age; Pregnancy; Prenatal Diagnosis; Quality of Life; United States
PubMed: 33466470
DOI: 10.3390/ijerph18010352 -
Genetics in Medicine : Official Journal... Apr 2020An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease.
PURPOSE
An entity of regression in Down syndrome (DS) exists that affects adolescents and young adults and differs from autism spectrum disorder and Alzheimer disease.
METHODS
Since 2017, an international consortium of DS clinics assembled a database of patients with unexplained regression and age- and sex-matched controls. Standardized data on clinical symptoms and tiered medical evaluations were collected. Elements of the proposed definition of unexplained regression in DS were analyzed by paired comparisons between regression cases and matched controls.
RESULTS
We identified 35 patients with DS and unexplained regression, with a mean age at regression of 17.5 years. Diagnostic features differed substantially between regression cases and matched controls (p < 0.001 for all but externalizing behaviors). Patients with regression had four times as many mental health concerns (p < 0.001), six times as many stressors (p < 0.001), and seven times as many depressive symptoms (p < 0.001). Tiered medical evaluation most often identified abnormalities in vitamin D 25-OH levels, polysomnograms, thyroid peroxidase antibodies, and celiac screens. Analysis of the subset of patients with nondiagnostic medical evaluations reinforced the proposed definition.
CONCLUSIONS
Our case-control evidence supports a proposed definition of unexplained regression in Down syndrome. Establishing this clinical definition supports future research and investigation of an underlying mechanism.
Topics: Adolescent; Autism Spectrum Disorder; Case-Control Studies; Databases, Factual; Down Syndrome; Humans; Young Adult
PubMed: 31767984
DOI: 10.1038/s41436-019-0706-8 -
American Journal of Human Genetics Nov 1983Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this... (Comparative Study)
Comparative Study
Preferential survival in older mothers of fetuses with Down syndrome has been proposed as contributing to the maternal-age effect of this condition. If correct, this provocative hypothesis, which may be termed "relaxed selection," has major implications for approaches to prevention of Down syndrome live births in older women. Several predictions of this hypothesis are examined here by comparisons of parental ages among various populations. These revealed that: (1) mean maternal age of Down syndrome live births is slightly lower than that of Down syndrome spontaneous fetal deaths; (2) mean maternal age of those with mutant D/21 translocation Down syndrome is about the same as that of controls; (3) the ages of Down syndrome mothers who have Down syndrome live births is slightly lower than ages of Down syndrome mothers who have unaffected live births; and (4) in recent data on 47, +21 cases in which the extra chromosome 21 is of paternal origin, the mean maternal ages are 4-5 years lower than the maternal ages of cases of maternal origin (in contrast to earlier reports). All of these observations are contrary to the hypothesis that relaxed selection contributes significantly to the maternal-age association of Down syndrome. If there is any effect of relaxed selection, it is likely to be very weak and/or act primarily upon abortions that occur before recognition of pregnancy.
Topics: Adult; Chromosomes, Human, 21-22 and Y; Down Syndrome; Female; Genotype; Humans; Infant, Newborn; Maternal Age; Models, Genetic; Pregnancy; Pregnancy, High-Risk; Selection, Genetic; Translocation, Genetic
PubMed: 6228139
DOI: No ID Found -
BMC Public Health Jun 2005The association between maternal age and risk of Down syndrome has been repeatedly shown in various populations. However, the effect of paternal age and education of... (Comparative Study)
Comparative Study
BACKGROUND
The association between maternal age and risk of Down syndrome has been repeatedly shown in various populations. However, the effect of paternal age and education of parents has not been frequently studied. Comparative studies on Down syndrome are also rare. This study evaluates the epidemiological characteristics of Down syndrome in two culturally and socially contrasting population settings, in California and the Czech Republic.
METHODS
The observed live birth prevalence of Down syndrome was studied among all newborns in the California counties monitored by California Birth Defects Monitoring Program from 1996 to 1997, and in the whole Czech Republic from 1994 to 1998. Logistic regression was used to analyze the data.
RESULTS
A total of 516,745 (California) and 475,834 (the Czech Republic) infants were included in the analysis. Among them, 593 and 251, respectively, had Down syndrome. The mean maternal age of children with Down syndrome was 32.1 years in California and 26.9 years in the Czech Republic. Children born to older mothers were at greater risk of Down syndrome in both populations. The association with paternal age was mostly explained by adjusting for maternal age, but remained significant in the Czech Republic. The association between maternal education and Down syndrome was much stronger in California than in the Czech Republic but parental age influences higher occurrence of Down syndrome both in California and in the Czech Republic.
CONCLUSION
The educational gradient in California might reflect selective impact of prenatal diagnosis, elective termination, and acceptance of prenatal diagnostic measures in Californian population.
Topics: Abortion, Induced; Adult; California; Czech Republic; Down Syndrome; Educational Status; Female; Humans; Infant, Newborn; Logistic Models; Male; Maternal Age; Middle Aged; Parents; Paternal Age; Pregnancy; Prenatal Diagnosis; Prevalence; Registries; Risk Assessment; Surveys and Questionnaires
PubMed: 15963229
DOI: 10.1186/1471-2458-5-69