Dementia in people with Down's syndrome

Tyrrell, Janette; Cosgrave, Mary; McCarron, Mary; McPherson, Janet; Calvert, Johnston; Kelly, Alan; McLaughlin, Martin; Gill, Michael; Lawlor, Brian A.

doi:10.1002/gps.502

Cited by 149 publications

(141 citation statements)

References 31 publications

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“…However, increased incidence of clinical signs of dementia in DS after the age of 50 years [29,54,63,66] appear to be at a later age than the first signs of significant insoluble Aβ accumulation or plaque accumulation and also after the first signs of neurofibrillary tangle pathology [35]. Thus, downstream events that may be directly or indirectly related to Aβ or tangle formation may lead to neuronal dysfunction and cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

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Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Nistor

Don

Parekh

et al. 2007

Neurobiology of Aging

110

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Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alphasecretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.

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Section: Discussionmentioning

confidence: 99%

“…Clinical signs of dementia are more commonly observed when individuals are over 50 years of age [4,29,49,63]. By age 40 years, however, all individuals with DS have neuropathological changes including senile plaques and neurofibrillary tangles consistent with AD [35,67,68].…”

Section: Introductionmentioning

confidence: 99%

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Nistor

Don

Parekh

et al. 2007

Neurobiology of Aging

110

View full text Add to dashboard Cite

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“…En individuos con síndrome de Down menores de 30 años, esta acumulación se manifiesta en forma de depósitos difusos que no están asociados con degeneración neurítica. Entre los 35 y 45 años, la acumulación del pépido β amiloide se acelera y aparecen otros signos como la acumulación de los ovillos neurofibrilares y neuroinflamación (8).…”

Section: Polimorfismos De Apoe En El Síndrome De Downunclassified

“…Los síntomas de la enfermedad de Alzheimer en los individuos con síndrome de Down aparecen en edades más tempranas que en los individuos normales (10). La edad en la cual aparece la demencia varía entre los 38 y los 70 años, y la edad promedio se encuentra entre los 50 y los 55 años y muchos de ellos desarrollarían la enfermedad a los 80 años (8,10).…”

Section: Polimorfismos De Apoe En El Síndrome De Downunclassified

Polimorfismos del gen ApoE en individuos con síndrome de Down y sus progenitores en una población colombiana

2012

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Introducción. Los polimorfismos en el gen ApoE se han examinado en el síndrome de Down debido a la relación existente de la isoforma E4 con la demencia de tipo Alzheimer que aparece en los individuos con síndrome de Down. Objetivos. Determinar los polimorfismos en el gen ApoE en individuos con síndrome de Down y sus progenitores, y buscar su asociación. Materiales y métodos. Mediante PCR-RFLP, se analizaron los polimorfismos del gen ApoE en 134 individuos jóvenes con síndrome de Down, 87 madres y 54 padres del eje cafetero, y se compararon con una población control de 525 individuos sanos. Resultados. El alelo APOEε3 y el genotipo ε3/ε3 fueron los más frecuentes en todas las poblaciones. La frecuencia alélica de APOEε2 es muy baja y ε2/ε2 está ausente en las poblaciones con síndrome de Down y sus progenitores. El alelo APOEε4 fue más frecuente en individuos con síndrome de Down que en el resto de poblaciones analizadas. Al comparar las frecuencias alélicas y genotípicas entre las poblaciones con síndrome de Down y los progenitores con la población control, mediante la χ 2 de Pearson y los odds ratios por la prueba exacta de Fisher, no se encontraron diferencias estadísticamente significativas. Conclusiones. No se encontró asociación entre los polimorfismos del gen ApoE y el síndrome de Down. Es posible que el tamaño de la muestra o las influencias étnicas hubieran afectado estos resultados. Es necesario hacer otros estudios en poblaciones colombianas y evaluar la asociación con otros genes que se encuentran relacionados con la enfermedad de Alzheimer.Palabras clave: apolipoproteínas E, síndrome de Down, enfermedad de Alzheimer, alelos, genotipo, Colombia. APOE gene polymorphisms associated with Down syndrome in Colombian populationsIntroduction. Gene APOEε4 allele polymorphisms have been examined in Down syndrome because of the relationship between (a) the E4 isoform and (b) the type of Alzheimer's dementia that appears in individuals with Down syndrome. This isoform is considered a risk factor for Alzheimer´s disease development and has been associated with early death in Down syndrome. Objectives. The polymorphisms in the APOE gene were characterized for Down syndrome individuals and their parents, in order to detect associations between the APOE polymorphisms and Down syndrome. Materials and methods. APOE gene polymorphisms were detected by RFLP-PCR and analyzed in 134 young individuals with Down syndrome, 87 mothers and 54 fathers, residents of the departments of Quindío and Risaralda, Colombia. The controls were 525 healthy individuals. Results. The APOEε3 allele and ε3/ε3 genotype were most frequent in all the populations (83-90% and 70-78%). The allelic frequency of APOEε2 was very low and ε2/ε2 (3-7%) was absent in Down syndrome and their parents. The allele APOEε4 was more frequent (11% vs. 9%) in Down syndrome individuals than in the controls. Comparing the allelic and genotypic frequencies between the populations with Down syndrome and their parents with the controls using Pearson χ 2 test and Fisher'...

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“…24 The prevalence of dementia in the non-Downs intellectually disabled population has been debated in the literature. Zigman et al 25 in a cross-sequential study of 126 adults with intellectual disability over the age of 65, performed a neuropsychological battery on participants screening positive for dementia using the DMR.…”

Section: A More Structured Environment Requiredmentioning

confidence: 99%

Deinstitutionalisation – time to move on to legislation?

Carrigan¹

2011

Ir. j. psychol. Med.

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The report represents a significant step forward in promoting the deinstitutionalisation agenda in Ireland, with its core recommendations being that all individuals with a disability living in 'congregated settings' (a residential setting where the person lives with 10 or more people) should be moved into the community and that the institutional settings in which they live should be closed.The General summary of the reportThe report has 31 recommendations. These describe a new model of support for people with disabilities in the community. The plan is to move individuals from institutional care to dispersed forms of housing in ordinary communities. The housing would be provided by local authorities and the individuals would access mainstream health and social services such as GP, home help and public health nursing. Other specialised services and hospital services would be provided based on individualised assessments.Ten of the recommendations directly refer to the financial resources required for the successful implementation of the report through funding support structures, purchasing and building accommodation and the provision of extra social welfare benefits for the group. It also notes that the disability budgets have been "reduced by a minimum of 5% in the period 2008-2010 and there is now less flexibility within budgets to fund further movement into the community within existing resources". 5 Deinstitutionalisation is generally a good thingCertainly the evidence internationally is that, in general, individuals with disabilities do better outside the institutional setting. One study by Young in 2006 of people with moderate to severe intellectual disability showed increased adaptive behaviour, choice-making and life quality in a group followed up after discharge from institutional living into a community setting. 6 The corollary has also been studied and Rutter has written extensively on the detrimental effects of institutionalisation. 7,8 The report itself cites a number of studies to support the case for community living both from a quality of life and costeffectiveness point of view. 9-12 However a study by Kozma, Mansell and Beadle-Brown is also mentioned in the report. In it 67 papers published between 1997 and 2007 were reviewed. In seven out of 10 areas (community presence and participation, social networks and friendships, family contact, self-determination and choice, quality of life, adaptive behaviour, user and family views and satisfaction) the majority of studies showed that community living was superior to institutional care.In three areas (challenging behaviour, psychotropic medication and health, risks and mortality) research reported mixed or worse results. 13 People with higher support needs -whether because of the nature of their intellectual and physical disabilities, their challenging behaviour or social impairment, often experience less good outcomes in the community than people who are more independent. 14 In the general context of deinstitutionalisation, they are also typically the...

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Dementia in people with Down's syndrome

Abstract: Dementia had a prevalence of 13.3% and occurred at a mean age of 54.7 years. The combination of DLSQ score, age and presence of epilepsy were found to predict presence of dementia.

Cited by 149 publications

References 31 publications

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain

Polimorfismos del gen ApoE en individuos con síndrome de Down y sus progenitores en una población colombiana

Deinstitutionalisation – time to move on to legislation?

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