P.0748 The impact of Alzheimer disease on the brain's white matter development in individuals with Down syndrome: a systematic review

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Abstract

Background: The brain’s white matter trajectories during the pre-clinical stages of Alzheimer disease (AD) are not fully understood. Individuals with genetic risks for AD, such as those with autosomal dominant AD present an opportunity
to examine the earliest brain abnormalities but are rare and represents only 1% of the total cases of AD [1] . Down syndrome (DS), the main genetic cause of learning disabilities, has long been established as having a high risk for AD due to amyloid over production due to triplication of the APP gene on chromosome 21, offering an opportunity to study lifelong developmental trajectories associated with AD development [2]. Indeed, by the age of 30, virtually every individual with DS presents with the histological features of AD, until the age of 50, when early AD symptoms emerge.
Objective: To identify the pattern of white matter microstructural integrity loss peculiar to pre-clinical stages of AD, in a population at ultra-high risk of developing AD.
Method: A systematic literature review on diffusion MRI based studies investigating structural connectivity in DS was carried out. We searched electronic databases (MEDLINE, 1946 to September 2020; EMBASE 1974 to September 2020;
PsychInfo, 1806 to September 2020) to identify relevant articles using the following key words: Down syndrome or trisomy 21 in combination with white matter, structural connectivity, diffusion MRI, diffusion imaging, DTI, TBSS, and
fractional anisotropy. Titles and abstracts of the identified articles were assessed against the following inclusion criteria: (a) participant with diagnosis of DS; (b) inclusion of healthy controls; (c) use of diffusion MRI techniques. Articles
were excluded if written in languages other than English and if the study employed techniques other than diffusion MRI.
Results: The search strategy identified 279 articles. After screening titles and abstract, 8 pertinent remained (5 articles and 2 conference presentations). All these crosssectional investigations reported microstructural integrity alterations in the corpus callosum as well as in most of the long association fibres (superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and cingulum bundle) in both children and adult with DS, when compared to agematched healthy controls [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The potential functional associations deriving from such neural connectivity
abnormalities have been described in terms of language, executive, and motor functions impairments [ 3 , 7 ]. Finally, a further and progressive microstructural integrity loss was observed in the genu and splenium of corpus callosum as
well as in the cingulum bundle, with the progression form pre-clinical to mild cognitive impairment to clinical stages of AD in this population [9] .
Conclusion: In individuals with DS, which is a population at ultra-high risk of AD, microstructural integrity loss of all the main association fibres can be observed in both preclinician, prodromal, and clinical stages of AD. Moreover, corpus callosum and cingulum bundle integrity loss has been identified as early sign of disease progression. In conclusion, the white matter neurodegeneration in population with DS closely resembles that of sporadic AD [10] , highlighting the
importance of research in DS to identify MRI-based early biomarkers of AD.
Original languageEnglish
Title of host publicationEuropean Neuropsychopharmacology - 34th ECNP Congress – Lisbon 2021 Hybrid
PublisherEuropean Neuropsychopharmacology
Pages544-545
Number of pages2
Volume53
DOIs
Publication statusPublished - Dec 2021

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