Sarah Hamburg

University College London | UCL · Division of Psychiatry

Down syndrome (DS) is associated with an ultra-high risk of developing Alzheimer's disease (AD). Understanding variability in pre-AD cognitive abilities may help understand cognitive decline in this population. The mismatch negativity (MMN) is an event-related potential component reflecting the detection of deviant stimuli that is thought to repres...

Background: People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeut...

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 ad...

Background Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) worldwide. Understanding electrophysiological characteristics associated with DS provides potential mechanistic insights into ID, helping inform biomarkers and targets for intervention. Currently, electrophysiological characteristics associated with DS re...

Cells from people with Down syndrome (DS) show faster accumulation of DNA damage and epigenetic aging marks. Causative mechanisms remain un-proven and hypotheses range from amplified chromosomal instability to actions of several supernumerary chromosome 21 genes. Plasma immunoglobulin G (IgG) glycosylation profiles are established as a reliable pre...

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-invas...

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....

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 Emax models were fitted to longitudinal cognitive data...

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. Here we investigate associat...

A population of >6 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 sampl...

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,...

Background: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences b...

Individuals with Down syndrome (DS) show high inter-subject variability in cognitive ability and have an ultra-high risk of developing dementia (90% lifetime prevalence). Elucidating factors underlying variability in cognitive function can inform us about intellectual disability (ID) and may improve our understanding of factors associated with late...

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 Sca...

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 Sca...

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 understa...

Down syndrome (DS) is the most common genetic cause of intellectual disability. There is, however, considerable variation in cognitive abilities between those with DS, with some individuals scoring at floor on some tests, particularly for age-standardised outcomes. This variation and these floor effects can pose a problem for comparing and combinin...

Down syndrome (DS) is the most common genetic cause of intellectual disability. There is, however, considerable variation in cognitive abilities between those with DS, with some individuals scoring at floor on some tests, particularly for age-standardised outcomes. This variation and these floor effects can pose a problem for comparing and combinin...

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 underst...

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 longi...

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 la...

Individuals with Down syndrome (DS) show a high degree of inter-subject variability in cognitive ability. Elucidating factors associated with variability in cognitive function can inform us about intellectual disability severity and potentially provide biomarkers of ability for clinical trials targeting cognition in individuals with DS (including t...

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 compli...

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 complica...

Down syndrome (DS), the most common genetic cause of intellectual disability, is characterised by a pattern of cognitive deficits hypothesised as relating to later developing neural systems. Multisensory integration (MSI) has been shown to benefit cognitive performance on numerous tasks in the typically developing population and is implicated in th...

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 de...

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 c...

Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). Abilities relating to executive function, memory and language are particularly affected in DS, although there is a large variability across individuals. People with DS also show an increased risk of developing dementia. While assessment batteries have been develope...