Dementia and mortality in persons with Down’s syndrome

Coppus, Antonia; Evenhuis, Heleen M.; Verberne, Gert-Jan; Visser, Frank E.; Gool, Pim van; Eikelenboom, Piet; Duijin, C. van

doi:10.1111/j.1365-2788.2006.00842.x

Cited by 224 publications

(199 citation statements)

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“…1). Thus, as with AD in the general population, age is a strong independent risk factor for AD-DS 21 . By the age of 65, 68-80% of individuals with DS have been shown to have developed dementia 6,7 (FIG.…”

Section: Prevalence Of Ad-dsmentioning

confidence: 88%

“…The average age at which menopause begins in women with DS correlates with the age of onset of dementia 24-26 ; however, unlike the incidence of AD in euploid individuals, gender does not affect the incidence of AD-DS 20,21 . The reasons for this difference between the two populations are unknown, although it is possible that trisomy may cause changes in hormonal or cardiovascular biology that alter AD risk.…”

Section: Prevalence Of Ad-dsmentioning

confidence: 99%

“…Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population. Down syndrome (DS) is a complex, highly variable disorder that arises from trisomy of chromosome 21. It was one of the first chromosomal disorders to be identified 1 and occurs with an incidence of approximately 1 in 800 births 2 .…”

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A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

et al. 2015

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Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) -an Alzheimer disease risk factor -although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.Down syndrome (DS) is a complex, highly variable disorder that arises from trisomy of chromosome 21. It was one of the first chromosomal disorders to be identified 1 and occurs with an incidence of approximately 1 in 800 births 2 . Its prevalence within a given population is influenced by infant mortality rates, access to health care, termination rates, average maternal age 3 and life expectancy. Indeed, despite the increased availability of prenatal diagnosis and access to the option of termination, the global prevalence of DS is rising because of improvements in life expectancy: the number of adults with DS aged over 40 years has doubled in northern Europe since 1990 and, in the United Kingdom, one-third of the estimated 40,000 people with DS are thought to be over 40 years of age 4 .DS is the most common form of intellectual disability. In addition to the features that are found in everyone with the disorder, such as the characteristic facial dysmorphology, there are many DS-associated phenotypes that have variable penetrance and severity. For example, approximately 40% of individuals with DS have heart malformations (usually atrioventricular septal defects) 5 . A key feature of DS is a striking propensity to develop early-onset Alzheimer disease (EOAD). Complete trisomy of chromosome 21 universally causes the development of amyloid plaques and neurofibrillary tangles (NFTs), which are typical characteristics of AD brain pathology, by the age of 40, and approximately twothirds of individuals with DS develop dementia by the age of 60 (REFS 6,7). However, rates of dementia do not reach 100%, even in older individuals, suggesting that some individuals with DS are protected from the onset of AD (FIG. 1).All of the features of DS arise because of aberrant dosages of coding and/or non-coding sequences present on chromosome 21. Among these sequences, the gene encoding amyloid precursor protein (APP) is thought to have a key role in the pathology of AD. The additional copy of APP may drive the development of AD in individuals with DS (AD-DS) by increasing the levels of amyloid-β (Aβ), a cleavage product of APP that misfolds and accumulates in the brain in people with AD. Consistent with this hypothesis, individuals with small internal chromosome 21 duplications that result in three copies of APP -a rare familial trait known as duplic...

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Section: Prevalence Of Ad-dsmentioning

confidence: 88%

Section: Prevalence Of Ad-dsmentioning

confidence: 99%

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A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

et al. 2015

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“…in sizes of the prefrontal cortex, cerebellum, hippocampus, amygdala, and brain stem in newborn individuals with DS (Aylward et al, 1997;Dierssen, 2012;Guidi et al, 2008), and structural abnormalities such as reduced dendritic and axonal number and volume, and altered synaptic plasticity (L. Becker, Mito, Takashima, & Onodera, 1991;Coppus et al, 2006;Dierssen, 2012). These brain deficits in individuals with DS are associated with cognitive and intellectual deficits including memory deficiencies, and motor dysfunction.…”

Section: Individuals With Ds Display Developmental Alterations In Bramentioning

confidence: 99%

Low dose EGCG treatment beginning in adolescence does not improve cognitive impairment in a Down syndrome mouse model

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et al. 2015

Pharmacology Biochemistry and Behavior

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“…The actual rate of conversion varies among studies, but the most recent data on 506 individuals with DS (ages show the highest prevalence of dementia is 32.1% in the age group 55-59; the rate is 17.7% in 50-54 year olds and 8.9% in 45-49 year olds (Coppus, Evenhuis et al 2006). We conducted a prospective study using PET and MRI starting with middle-aged persons with DS, none of whom showed clinical signs of dementia when they entered the study.…”

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confidence: 99%