Search

Background: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome., Objective/hypothesis: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome., Methods: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) located across the United States and in the United Kingdom enrolled in the Alzheimer's Biomarker Research Consortium on Down Syndrome (ABC-DS) completed a survey., Results: The residence of 17% of individuals was altered, and 89% of those who had been employed stopped working during the pandemic. One-third (33%) of individuals were reported to be more irritable or easily angered, 52% were reported to be more anxious, and 41% were reported to be more sad/depressed/unhappy relative to prepandemic. The majority of changes in mood and behavior were of modest severity., Conclusions: The COVID-19 pandemic has had widespread effects on the daily life and mood and behavior of adults with Down syndrome. In the short term, caregivers and providers should be prepared to help adults with Down syndrome with changes in daily routines, residence, employment, or adult disability day programs as society shifts away from COVID-19 safety protocols., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro 3 H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (n = 25) and DS (n = 39). In DS, 3 H-PiB binding was significantly associated with age. After age 40 years in DS, 3 H-PiB binding rose dramatically along with increasing individual variability. 3 H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and cerebral amyloid angiopathy in DS brain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This chapter reviews the neurological phenotype of Down syndrome (DS) in early development, childhood, and aging. Neuroanatomic abnormalities in DS are manifested as aberrations in gross brain structure as well as characteristic microdysgenetic changes. As the result of these morphological abnormalities, brain circuitry is impaired. While an intellectual disability is ubiquitous in DS, there is a wide range of variation in cognitive performance and a growing understanding between aberrant brain circuitry and the cognitive phenotype. Hypotonia is most marked at birth, affecting gait and ligamentous laxity. Seizures are bimodal in presentation with infantile spasms common in infancy and generalized seizures associated with cognitive decline observed in later years. While all individuals have the characteristic neuropathology of Alzheimer's disease (AD) by age 40 years, the prevalence of dementia is not universal. The tendency to develop AD is related, in part, to several genes on chromosome 21 that are overexpressed in DS. Intraneuronal accumulation of β-amyloid appears to trigger a cascade of neurodegeneration resulting in the neuropathological and clinical manifestations of dementia. Functional brain imaging has elucidated the temporal sequence of amyloid deposition and glucose metabolic rate in the development of dementia in DS. Mitochondrial abnormalities contribute to oxidative stress which is part of AD pathogenesis in DS as well as AD in the general population. A variety of medical comorbidities threaten cognitive performance including sleep apnea, abnormalities in thyroid metabolism, and behavioral disturbances. Mouse models for DS are providing a platform for the formulation of clinical trials with intervention targeted to synaptic plasticity, brain biochemistry, and morphological brain alterations., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Abeta) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Abeta degradation and clearance.

There is evidence to suggest that certain shared features exist in the pathogenesis of vascular disease and Alzheimer disease (AD) in the general population. In Down syndrome (DS) all adults over the age of 40 years develop sufficient neuropathology for a diagnosis of AD. However, vascular disease is not as common in DS as it is in the general population, particularly with respect to the development of atheromas. We discuss biological mechanisms and risk factors that may be common to both diseases including cholesterol metabolism, inflammation, plasminogen activator inhibitor and apolipoprotein E (Apo E). The study of individuals with DS may help to identify common pathogenic links as well as a disassociation between vascular disease and AD.

The contribution of the cerebral cortex to the generation of sensory evoked potentials was studied in an infant with hydranencephaly. On CT scan no tissue above the thalamus was noted. Long-latency potentials to auditory stimuli were absent whereas the short-latency or brain-stem auditory evoked potentials and some of the components of the middle latency auditory evoked potentials (No and Po) were present. To visual stimulation only the electroretinogram was detected. To somatosensory stimulation only the spinal cord potentials could be detected. The absence of long-latency components in each of the sensory modalities supports the concept that these potentials require intact cerebral hemispheres in man.