The First Confirmed Case of Down Syndrome with Dementia with Lewy Bodies

Airuehia, Efosa; Carey, Manus

doi:10.1111/j.1468-3148.2009.00526.x

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Two participants diagnosed with dementia in the cohort showed no PIB binding. Similar findings have been reported by the Alzheimer's Disease Neuroimaging Initiative PET core, showing that 10%–20% of their clinically diagnosed AD subjects are PIB-negative [39] with the suggestion that these could represent the presence of non-AD dementia [40] . Although the two apparently demented PIB-negative subjects in the present series might also represent non-AD pathology, it is probably more likely a reflection of the occasional difficulty in making an accurate early dementia diagnosis in the DS population.…”

Section: Discussionsupporting

confidence: 84%

The pattern of amyloid accumulation in the brains of adults with Down syndrome

Annus

Wilson

Hong

et al. 2015

Alzheimer's & Dementia

157

182

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IntroductionAdults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis.MethodsForty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status.ResultsAbnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function.DiscussionPIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.

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Section: Discussionsupporting

confidence: 84%

The pattern of amyloid accumulation in the brains of adults with Down syndrome

Annus

Wilson

Hong

et al. 2015

Alzheimer's & Dementia

157

182

View full text Add to dashboard Cite

show abstract

“…Neuronal accumulation of ubiquitylated and aggregated transactive response DNA-binding protein 43 (TDP43; also known as TARDBP) in the cytoplasm and neurites is similar in AD-DS (7-14% of cases) and familial AD (10-14% of cases), whereas TDP43 neuropathology occurs more frequently in LOAD (29-79% of cases), perhaps because of the later disease onset 101,102 . Lewy bodies, particularly in the amygdala, occur at a similar frequency in AD-DS and LOAD 103 , but dementia with Lewy bodies (DLB), which is characterized by cognitive decline with hallucinations and parkinsonism features, is rare in DS 104 . Granulovacuolar degeneration, the formation of electron-dense granules in doublemembrane-bound cytoplasmic vacuoles, associated with plaque and NFT pathology occurs at a similar frequency in AD-DS and AD 64 .…”

Section: Neuropathological Changes In Ad-dsmentioning

confidence: 99%

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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“…There is notable overlap of symptoms between subcortical dementias such as Dementia with Lewy Bodies (DLB) and later life symptoms of Down’s syndrome (Prasher et al , 2010). Key differential subtleties are a motivational syndromes and psychoses, which are more prone in comorbid DLB than in three Down’s syndrome alone (Simard and van Reekum, 2001).…”

Section: Discussionmentioning

confidence: 99%

Significance of Basal ganglia calcification in Down's syndrome

Thoms

Idowu

Nehra

et al. 2020

AMHID

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Purpose There is high incidence of dementia in individuals with Down’s syndrome. Much of the emphasis has been on Alzheimer’s disease as being most prevalent; however, it is apparent that other dementia types are also likely, to which this patient cohort may be predisposed. Specifically, this paper aims to highlight the potential for subcortical dementias in Down’s syndrome, suggesting a role for broader cognitive screening in aging individuals. Design/methodology/approach This paper describes a case of a female with Down’s syndrome and mild intellectual disability who presented with early signs of distinctive cognitive impairment and radiological calcification of the basal ganglia. Findings An active 42-year-old lady, who was mostly independent of activities of daily living and in part-time employment, presented with a three-year history of progressive cognitive deficit, characteristic of subcortical decline. She had no personal or known family history of mental illness, epilepsy or dementia. Routine blood tests showed chronic renal impairment, mild hypocalcaemia and vitamin D deficiency, managed by her GP. CT scan showed only bilateral basal ganglia calcification. Originality/value There is a widespread appreciation for the link between Down’s syndrome and Alzheimer’s disease but lesser consideration of the possibility of subcortical dementias. Given the differential nature and presentation of the two dementias, this case report highlights a need for clinicians to consider both to effectively manage these patients in the longer-term. Screening is discussed as a potential means of achieving this.

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The First Confirmed Case of Down Syndrome with Dementia with Lewy Bodies

Cited by 6 publications

References 27 publications

The pattern of amyloid accumulation in the brains of adults with Down syndrome

The pattern of amyloid accumulation in the brains of adults with Down syndrome

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

Significance of Basal ganglia calcification in Down's syndrome

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