Pehrsonhovgaard3267

Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages.

We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria.

There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests.

We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

We evaluated for two novel automated biomarker assays how cerebrospinal fluid (CSF) amyloid beta (Aβ)

-ratios improved the concordance with amyloid positron emission tomography (PET) positivity compared to Aβ

alone.

We selected 288 individuals from the Amsterdam Dementia Cohort across the Alzheimer's disease clinical spectrum when they had both CSF and amyloid PET visual read available, regardless of diagnosis. CSF Aβ

, phosphorylated tau (p-tau), and total tau (t-tau) were measured with Elecsys and Lumipulse assays, and Aβ

with Lumipulse. CSF cut-points were defined using receiver operating characteristic (ROC) for amyloid PET positivity.

For both Elecsys and Lumipulse the p-tau/Aβ

, Aβ

/Aβ

, and t-tau/Aβ

ratios showed similarly good concordance with amyloid PET (Elecsys 93,90,90%; Lumipulse 94,92,90%) and were higher than Aβ

alone (Elecsys 85%; Lumipulse 84%).

Biomarker ratios p-tau/Aβ

, Aβ

/Aβ

, t-tau/Aβ

on two automated platforms show similar optimal concordance with amyloid PET in a memory clinic cohort.

Biomarker ratios p-tau/Aβ1- 42, Aβ1- 42/Aβ1- 40, t-tau/Aβ1- 42 on two automated platforms show similar optimal concordance with amyloid PET in a memory clinic cohort.

This study aimed to investigate cognitive aging trajectories, the associated sociodemographic characteristics, and the association of these trajectories with dementia.

Generally healthy older adults (n=19,114) were followed for up to 7 years, with regular cognitive assessments. Group-based trajectory modeling identified distinct cognitive trajectories.

Four to seven trajectories were identified per cognitive domain. Stable trajectories were observed across domains. Improvement in verbal fluency and minor psychomotor slowing were common. Substantial decline in global cognition and episodic memory were observed in a small proportion of individuals. Older, less educated participants and men were more common in lower-functioning trajectories (

<.001). The highest proportions of dementia cases were in trajectories with major decline in global cognition (56.9%) and memory (33.2%).

Inter-individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.

Inter-individual variability in cognitive trajectories was observed across all domains. Some individuals appear resilient to cognitive decline even with advancing age. Further research into factors promoting cognitive resilience is needed.

Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed.

Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37).

Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased.

We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. OSI930 The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.

We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.[This corrects the article DOI 10.1002/dad2.12112.].The search for new, robust, and reproducible biomarkers for Alzheimer's disease (AD) diagnosis is a challenge. We recently reported that salivary lactoferrin (Lf) could be presented as new biomarker candidate for AD, being both non-invasive and cost-effective, as well as having appropriate diagnostic performance for the clinical detection of AD subjects. Saliva is an attractive sample type for biomarker-based testing approaches for several other diseases; however, its composition may change under certain circumstances. It is therefore critical to maintain a consistent salivary handling protocol, considering possible extrinsic factors that may influence salivary Lf concentration. In this work, we analyzed salivary Lf concentration under different handling conditions and donor-dependent factors including age, inter-diurnal variations, physical activity, and pharmacological treatments. Our aim was to evaluate the influence of such conditions on salivary Lf concentration. In conclusion, we found that most of these extrinsic factors should be considered in the future when using Lf as a predictive biomarker for AD.

Cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) are biomarkers of Alzheimer's disease (AD), yet much is unknown about AD-associated changes in tau metabolism and tau tangle etiology.

We assessed the variation of t-tau and p-tau explained by 38 previously identified CSF metabolites using linear regression models in middle-age controls from the Wisconsin Alzheimer's Disease Research Center, and predicted AD/mild cognitive impairment (MCI) versus an independent set of older controls using metabolites selected by the least absolute shrinkage and selection operator (LASSO).

The 38 CSF metabolites explained 70.3% and 75.7% of the variance in t-tau and p-tau, respectively. Of these, seven LASSO-selected metabolites improved the prediction ability of AD/MCI versus older controls (area under the curve score increased from 0.92 to 0.97 and 0.78 to 0.93) compared to the base model.

These tau-correlated CSF metabolites increase AD/MCI prediction accuracy and may provide insight into tau tangle etiology.