Eye Tracking as a Tool for Detecting Alzheimer's Disease in People With Down Syndrome.

Background: Adults with Down syndrome (DS) experience an increased risk of Alzheimer's disease (AD). Valid cognitive assessments for adults with DS with severe/profound intellectual disability (ID) are needed. It is unclear whether eye tracking is feasible for detecting AD in DS.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).

Multimodal neuroimaging biomarkers and subtle cognitive decline in a population-based cohort without dementia.

Background: The relationship between subtle cognitive decline and Alzheimer's disease (AD) pathology as measured by biomarkers in settings outside of specialty memory clinics is not well characterized.

Objective: To investigate how subtle longitudinal cognitive decline relates to neuroimaging biomarkers in individuals drawn from a population-based study in an economically depressed, small-town area in southwestern Pennsylvania, USA.

Methods: A subset of participants without dementia (N = 115, age 76.

The striatum is an early, accurate indicator of amyloid burden using [C]PiB in Down syndrome: comparison of two radiotracers.

Introduction: Adults with Down syndrome demonstrate striatum-first amyloid accumulation with [C]PiB PET imaging, which has not been replicated with [F]florbetapir (FBP). Early striatal accumulation has not been temporally quantified with respect to global cortical measures.

Methods: Longitudinal PiB (n=175 participants) and FBP (n=92 participants) data from the Alzheimer Biomarkers Consortium-Down Syndrome were used to measure cortical and striatal binding.

Kinetic modeling of the monoamine oxidase-B radioligand [F]SMBT-1 in human brain with positron emission tomography.

This paper describes pharmacokinetic analyses of the monoamine-oxidase-B (MAO-B) radiotracer [F]()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([F]SMBT-1) for positron emission tomography (PET) brain imaging. Brain MAO-B expression is widespread, predominantly within astrocytes. Reactive astrogliosis in response to neurodegenerative disease pathology is associated with MAO-B overexpression.

AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome.

Introduction: Down syndrome (DS) is a genetic cause of early-onset Alzheimer's disease (AD). The National Institute on Aging-Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS.

Method: Data are from the Alzheimer's Biomarker Consortium-Down Syndrome.

MISPEL: A supervised deep learning harmonization method for multi-scanner neuroimaging data.

Large-scale data obtained from aggregation of already collected multi-site neuroimaging datasets has brought benefits such as higher statistical power, reliability, and robustness to the studies. Despite these promises from growth in sample size, substantial technical variability stemming from differences in scanner specifications exists in the aggregated data and could inadvertently bias any downstream analyses on it. Such a challenge calls for data normalization and/or harmonization frameworks, in addition to comprehensive criteria to estimate the scanner-related variability and evaluate the harmonization frameworks.

Timing of Alzheimer's Disease by Intellectual Disability Level in Down Syndrome.

Background: Trisomy 21 causes Down syndrome (DS) and is a recognized cause of early-onset Alzheimer's disease (AD).

Objective: The current study sought to determine if premorbid intellectual disability level (ID) was associated with variability in age-trajectories of AD biomarkers and cognitive impairments. General linear mixed models compared the age-trajectory of the AD biomarkers PET Aβ and tau and cognitive decline across premorbid ID levels (mild, moderate, and severe/profound), in models controlling trisomy type, APOE status, biological sex, and site.

Striatal dopamine supports reward expectation and learning: A simultaneous PET/fMRI study.

Converging evidence from both human neuroimaging and animal studies has supported a model of mesolimbic processing underlying reward learning behaviors, based on the computation of reward prediction errors. However, competing evidence supports human dopamine signaling in the basal ganglia as also contributing to the generation of higher order learning heuristics. Here, we present data from a large (N = 81, 18-30yo), multi-modal neuroimaging study using simultaneously acquired task fMRI, affording temporal resolution of reward system function, and PET imaging with [C]Raclopride (RAC), assessing striatal dopamine (DA) D2/3 receptor binding, during performance of a probabilistic reward learning task.

Weight Loss and Alzheimer's Disease in Down Syndrome.

Background: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD) pathology, but research gaps remain in understanding early signs of AD in DS.

Objective: The goal of the present study was to determine if unintentional weight loss is part of AD in DS. The specific aims were to: 1) examine relation between chronological age, weight, AD pathology, and AD-related cognitive decline were assessed in a large cohort of adults with DS, and 2) determine if baseline PET amyloid-β (Aβ) and tau PET status (-versus+) and/or decline in memory and mental status were associated with weight loss prior to AD progression.

Physical activity, memory function, and hippocampal volume in adults with Down syndrome.

Higher engagement in moderate-intensity physical activity (PA) is related to better cognitive functioning in neurotypical adults; however, little is known about the effect of PA on cognitive aging in adults with Down syndrome (DS). Individuals with DS have three copies of chromosome 21, which includes the gene involved in the production of the amyloid precursor protein, resulting in an increased risk for an earlier onset of Alzheimer's disease (AD). The goal of this study was to understand the relationship between engagement in moderate PA, memory, and hippocampal volume in adults with DS.

Amyloid- β and tau deposition influences cognitive and functional decline in Down syndrome.

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [F]-AV1451 and PET [C]PiB scans to quantify tau deposition in Braak regions II-VI and the Striatum and amyloid-β status respectively. Linear Mixed Effects models were implemented to assess how tau and amyloid-β deposition are related to change over three time points.

White matter microstructure associations to amyloid burden in adults with Down syndrome.

Introduction: Individuals with Down syndrome (DS) are at an increased risk of developing Alzheimer's Disease (AD). One of the early underlying mechanisms in AD pathology is the accumulation of amyloid protein plaques, which are deposited in extracellular gray matter and signify the first stage in the cascade of neurodegenerative events. AD-related neurodegeneration is also evidenced as microstructural changes in white matter.

A multi-scanner neuroimaging data harmonization using RAVEL and ComBat.

Modern neuroimaging studies frequently combine data collected from multiple scanners and experimental conditions. Such data often contain substantial technical variability associated with image intensity scale (image intensity scales are not the same in different images) and scanner effects (images obtained from different scanners contain substantial technical biases). Here we evaluate and compare results of data analysis methods without any data transformation (RAW), with intensity normalization using RAVEL, with regional harmonization methods using ComBat, and a combination of RAVEL and ComBat.

Acute Regression in Down Syndrome.

Background: Acute regression has been reported in some individuals with Down syndrome (DS), typically occurring between the teenage years and mid to late 20s. Characterized by sudden, and often unexplained, reductions in language skills, functional living skills and reduced psychomotor activity, some individuals have been incorrectly diagnosed with Alzheimer's disease (AD).

Methods: This paper compares five individuals with DS who previously experienced acute regression with a matched group of 15 unaffected individuals with DS using a set of AD biomarkers.

Physical activity and cognitive and imaging biomarkers of Alzheimer's disease in down syndrome.

Adults with Down syndrome (DS) are at risk for Alzheimer's disease. Despite sharing trisomy 21, however, there is variability in the age of disease onset. This variability may mean that other factors, such as lifestyle, influence cognitive aging and disease timing.

Characterization of point-spread function specification error on Geometric Transfer Matrix partial volume correction in [C]PiB amyloid imaging.

Purpose: Partial-volume correction (PVC) using the Geometric Transfer Matrix (GTM) method is used in positron emission tomography (PET) to compensate for the effects of spatial resolution on quantitation. We evaluate the effect of misspecification of scanner point-spread function (PSF) on GTM results in amyloid imaging, including the effect on amyloid status classification (positive or negative).

Methods: Twenty-nine subjects with Pittsburgh Compound B ([C]PiB) PET and structural T1 MR imaging were analyzed.

Neurofibrillary tau depositions emerge with subthreshold cerebral beta-amyloidosis in down syndrome.

Introduction: Adults with Down syndrome are genetically predisposed to develop Alzheimer's disease and accumulate beta-amyloid plaques (Aβ) early in life. While Aβ has been heavily studied in Down syndrome, its relationship with neurofibrillary tau is less understood. The aim of this study was to evaluate neurofibrillary tau deposition in individuals with Down syndrome with varying levels of Aβ burden.