Article

Fifteen-year follow-up of 92 hospitalized adults with Down’s syndrome: Incidence of cognitive decline, its relationship to age and neuropathology. Journal of Intellectual Disability Research, 51, 463-477

Newcastle University, Newcastle-on-Tyne, England, United Kingdom
Journal of Intellectual Disability Research (Impact Factor: 2.41). 07/2007; 51(Pt. 6):463-77. DOI: 10.1111/j.1365-2788.2006.00902.x
Source: PubMed

ABSTRACT

The clinical and neuropathological features associated with dementia in Down's syndrome (DS) are not well established. Aims To examine clinico-pathological correlations and the incidence of cognitive decline in a cohort of adults with DS.
A total of 92 hospitalized persons with DS were followed up from 1985 to December 2000. At outset, 87 participants were dementia-free, with a median age of 38 years. Assessments included the Prudhoe Cognitive Function Test (PCFT) and the Adaptive Behavior Scale (ABS), to measure cognitive and behavioural deterioration. Dementia was diagnosed from case records and caregivers' reports.
Eighteen (21%) patients developed dementia during follow-up, with a median age of onset 55.5 years (range 45-74). The PCFT demonstrated cognitive decline among those with a less severe intellectual disability (mild and moderate) but not among the profoundly disabled people (severe and profound). Clinical dementia was associated with neuropathological features of Alzheimer's disease, and correlated with neocortical neurofibrillary tangle densities. At the age of 60 years and above, a little more than 50% of patients still alive had clinical evidence of dementia.
Clinical dementia associated with measurable cognitive and functional decline is frequent in people with DS after middle age, and can be readily diagnosed among less severely intellectually disabled persons using measures of cognitive function such as the PCFT and behavioural scales such as the ABS. In the more profoundly disabled people, the diagnosis of dementia is facilitated by the use of behavioural and neurological criteria. In this study, the largest prospective DS series including neuropathology on deceased patients, the density of neurofibrillary tangles related more closely to the dementia of DS than senile plaques. In people with DS surviving to middle and old age, the development of dementia of Alzheimer type is frequent but not inevitable, and some people with DS reach old age without clinical features of dementia.

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Available from: Stephen Tyrer, Feb 25, 2015
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    • "Histological changes typical of Alzheimer's disease (AD) are constantly reported in autopsied brain tissue of deceased individuals with Down syndrome (trisomy 21) older than 30–40 years [1] [2] [3]. This fact suggests the important role that the overexpression of genes encoded on the 21st chromosome plays in the development of AD. "

    Full-text · Dataset · Jul 2015
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    • "Histological changes typical of Alzheimer's disease (AD) are constantly reported in autopsied brain tissue of deceased individuals with Down syndrome (trisomy 21) older than 30–40 years [1] [2] [3]. This fact suggests the important role that the overexpression of genes encoded on the 21st chromosome plays in the development of AD. "
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    ABSTRACT: Morphological abnormalities observed typically in the brains of adults with Down syndrome are identical with those present in patients with Alzheimer's disease. However, only some adults with Down syndrome suffer from early dementia, whereas others remain unaffected. We aimed to identify the genomic background responsible for this observation. We performed cognitive assessment and genome expression analysis of blood mononuclear cells in seniors with Down syndrome. Unaffected elderly patients and younger patients with severe cognitive disability or cognitive deterioration differed significantly with regard to the MTRNR2L12 gene. Our findings suggest the potential value of this gene as a blood marker of early dementia in individuals with Down syndrome.
    Full-text · Article · Feb 2015 · Journal of Alzheimer's disease: JAD
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    • "The dotted line may be inflected, as when degeneration sets in after a period of ongoing skill development. Individuals with Down syndrome have relatively stable neurocognitive deficits until mid-life, when many develop dementia (Lott et al. 2012; Margallo-Lana et al. 2007). "
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