Exploring semantic verbal fluency patterns and their relationship to age and Alzheimer's disease in adults with Down syndrome.

Introduction: Adults with Down syndrome (DS) are at ultra-high risk of developing Alzheimer's disease (AD), characterized by poor episodic memory and semantic fluency in the preclinical phase in the general population. We explored semantic fluency performance in DS and its relationship to age, AD, and blood biomarkers.

Methods: A total of 302 adults with DS at baseline and 87 at follow-up from the London Down Syndrome Consortium cohort completed neuropsychological assessments.

Diagnostic and prognostic performance and longitudinal changes in plasma neurofilament light chain concentrations in adults with Down syndrome: a cohort study.

Background: Adults with Down syndrome are at an ultra-high risk of Alzheimer's disease, but diagnosis of Alzheimer's disease in this population is challenging. We aimed to validate the clinical utility of plasma neurofilament light chain (NfL) for the diagnosis of symptomatic Alzheimer's disease in Down syndrome, assess its prognostic value, and establish longitudinal changes in adults with Down syndrome.

Methods: We did a multicentre cohort study, including adults with Down syndrome (≥18 years), recruited from six hospitals and university medical centres in France, Germany, Spain, the UK, and the USA, who had been assessed, followed up, and provided at least two plasma samples.

The Association between Physical Activity and CAMDEX-DS Changes Prior to the Onset of Alzheimer's Disease in Down Syndrome.

Background: People with Down syndrome are at ultra-high risk of developing Alzheimer's dementia. At present, there are no preventative or curative treatments. Evidence from sporadic Alzheimer's disease literature suggests that lifestyle factors including physical activity may help maintain cognitive and functional skills and reduce dementia risk.

Optimal age and outcome measures for Alzheimer's disease prevention trials in people with Down syndrome.

Introduction: People with Down syndrome (DS) typically develop Alzheimer's disease (AD) neuropathology before age 40, but a lack of outcome measures and longitudinal data have impeded their inclusion in randomized controlled trials (RCTs).

Methods: Cohort study. Event-based and dose-response E models were fitted to longitudinal cognitive data, to stage AD and determine the earliest ages of decline.

Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome.

Importance: Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The ε4 allele of the apolipoprotein E gene (APOE ε4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ε4 genotype is associated with an early cognitive advantage.

Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.

A population of more than six million people worldwide at high risk of Alzheimer's disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss.

Health comorbidities and cognitive abilities across the lifespan in Down syndrome.

Background: Down syndrome (DS) is associated with variable intellectual disability and multiple health and psychiatric comorbidities. The impact of such comorbidities on cognitive outcomes is unknown. We aimed to describe patterns of physical health and psychiatric comorbidity prevalence, and receptive language ability, in DS across the lifespan, and determine relationships with cognitive outcomes.

Validating the Cognitive Scale for Down Syndrome (CS-DS) to Detect Longitudinal Cognitive Decline in Adults With Down Syndrome.

Down syndrome (DS) is associated with intellectual disability and an ultra-high risk of developing dementia. Informant ratings are invaluable to assess abilities and related changes in adults with DS, particularly for those with more severe intellectual disabilities and/or cognitive decline. We previously developed the informant rated Cognitive Scale for Down Syndrome (CS-DS) to measure everyday cognitive abilities across memory, executive function, and language domains in adults with DS, finding CS-DS scores are a valid measure of general abilities, and are significantly lower for those with noticeable cognitive decline compared to those without decline.

Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer's disease.

Background: Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer's disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and controls will aid in understanding AD development in DS. We explored group differences in plasma concentrations of amyloid-β peptides and tau (as their accumulation is a characteristic feature of AD) and cytokines (as the inflammatory response has been implicated in AD development, and immune dysfunction is common in DS).

Cognitive markers of preclinical and prodromal Alzheimer's disease in Down syndrome.

Introduction: Down syndrome (DS) is associated with an almost universal development of Alzheimer's disease. Individuals with DS are therefore an important population for randomized controlled trials to prevent or delay cognitive decline, though it is essential to understand the time course of early cognitive changes.

Methods: We conducted the largest cognitive study to date with 312 adults with DS to assess age-related and Alzheimer's disease-related cognitive changes during progression from preclinical to prodromal dementia, and prodromal to clinical dementia.

Association of Dementia With Mortality Among Adults With Down Syndrome Older Than 35 Years.

Importance: This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS).

Objective: To explore the association of dementia associated with Alzheimer disease with mortality and examine factors associated with dementia in adults with DS.

Design, Settings And Participants: Prospective longitudinal study in a community setting in England.

Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.

Objective: Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.

Methods: We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals' disease stage.

The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome.

Background: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer's disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS.

Cognitive decline and dementia in Down syndrome.

Purpose Of Review: Alzheimer's disease is most likely universal in older individuals with Down syndrome, due to having three copies of the amyloid precursor protein gene, resulting in amyloid-beta plaque deposition. Down syndrome is an important population in which to consider clinical trials of treatments to prevent or delay the development of dementia. However, assessment of subtler cognitive changes is challenging due to the presence of intellectual disability.

Assessment of an incentivised scheme to provide annual health checks in primary care for adults with intellectual disability: a longitudinal cohort study.

Background: People with intellectual disabilities (ID) have many comorbidities but experience inequities in access to health care. National Health Service England uses an opt-in incentive scheme to encourage annual health checks of patients with ID in primary care. We investigated whether the first 3 years of the programme had improved health care of people with ID.

Carer-led health interventions to monitor, promote and improve the health of adults with intellectual disabilities in the community: a systematic review.

Using carers to help assess, monitor, or promote health in people with intellectual disabilities (ID) may be one way of improving health outcomes in a population that experiences significant health inequalities. This paper provides a review of carer-led health interventions in various populations and healthcare settings, in order to investigate potential roles for carers in ID health care. We used rapid review methodology, using the Scopus database, citation tracking and input from ID healthcare professionals to identify relevant research.

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe.

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity--or the number of items in a set--which is thought to rely on an "approximate number sense" (ANS) associated with parietal lobes.