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Microstate Changes Associated With Alzheimer's Disease in Persons With Down Syndrome.

ABSTRACT: Down syndrome (DS) is associated with development of dementia due to Alzheimer's disease (AD). However, due to considerable heterogeneity in intellectual function among persons with DS, it is difficult to assess whether a person with DS has developed dementia due to AD (DS-AD). EEG spectral power has previously shown very promising results with increased slowing in DS-AD compared to DS. However, another technique called microstates may be used to assess whole-brain dynamics and has to our knowledge not previously been investigated in either DS or DS-AD. The aim of the current study was to assess whether microstates could be used to differentiate between adults with DS, and DS-AD. We included EEGs from 10 persons with DS and 15 persons with DS-AD in the analysis. For the microstate analyses, we calculated four global maps, which were then back-fitted to all the EEGs. Lastly, we extracted the duration, occurrence, and coverage for each of the microstates. Here, we found the four archetypical maps as has previously been reported in the literature. We did not find any significant difference between DS and DS-AD but the largest difference in microstate duration between DS and DS-AD was found in microstate A and D. These findings are in line with structural MR studies showing that both the frontal and temporal lobes are affected in persons with DS-AD. Microstates may potentially serve as a diagnostic marker, but larger studies are needed to confirm these findings.

SUBMITTER: Musaeus CS

PROVIDER: S-EPMC6892825 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Microstate Changes Associated With Alzheimer's Disease in Persons With Down Syndrome.

Musaeus Christian Sandøe CS Salem Lise Cronberg LC Kjaer Troels Wesenberg TW Waldemar Gunhild G

Frontiers in neuroscience 20191128

Down syndrome (DS) is associated with development of dementia due to Alzheimer's disease (AD). However, due to considerable heterogeneity in intellectual function among persons with DS, it is difficult to assess whether a person with DS has developed dementia due to AD (DS-AD). EEG spectral power has previously shown very promising results with increased slowing in DS-AD compared to DS. However, another technique called microstates may be used to assess whole-brain dynamics and has to our knowle ...[more]

PMID: 31849579

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Project description:BackgroundAlzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome.MethodsWe did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid β peptides 1-42 and 1-40 and their ratio (Aβ1-42/1-40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate.FindingsBetween Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aβ1-42/1-40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life.InterpretationAlzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments.FundingInstituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.

Dataset Information

Microstate Changes Associated With Alzheimer's Disease in Persons With Down Syndrome.

Publications

Microstate Changes Associated With Alzheimer's Disease in Persons With Down Syndrome.

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