Unlocking Cognitive Analysis Potential in Alzheimer's Disease Clinical Trials: Investigating Hierarchical Linear Models for Analyzing Novel Measurement Burst Design Data.

Measurement burst designs typically administer brief cognitive tests four times per day for 1 week, resulting in a maximum of 28 data points per week per test for every 6 months. In Alzheimer's disease clinical trials, utilizing measurement burst designs holds great promise for boosting statistical power by collecting huge amount of data. However, appropriate methods for analyzing these complex datasets are not well investigated.

Evaluation of traditional and bootstrapped methods for assessing data-poor fisheries: a case study on tropical seabob shrimp () with an improved length-based mortality estimation method.

Background: Unrealistic model assumptions or improper quantitative methods reduce the reliability of data-limited fisheries assessments. Here, we evaluate how traditional length-based methods perform in estimating growth and mortality parameters in comparison with unconstrained bootstrapped methods, based on a virtual population and a case study of seabob shrimp ( Heller, 1862).

Methods: Size data were obtained for 5,725 seabob shrimp caught in four distinct fishing grounds in the Southwestern Atlantic.

A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests.

A Diffusion Model Account of Cognitive Variability in Healthy Aging and Mild Cognitive Impairment.

Within-person variation in cognitive performance is linked to pathological aging. Cognitive fluctuations have not been analyzed using cognitive process models, such as the diffusion model, to characterize which cognitive processes contribute to variability in cognition. We collected 21 daily assessments of attention and personality in younger adults, healthy older adults, and those with mild cognitive impairment.

The Influence of Personality Traits on Driving Behaviors in Preclinical Alzheimer Disease.

Introduction: Alzheimer disease (AD) has a long preclinical phase in which AD pathology is accumulating without detectable clinical symptoms. It is critical to identify participants in this preclinical phase as early as possible since treatment plans may be more effective in this stage. Monitoring for changes in driving behavior, as measured with GPS sensors, has been explored as a low-burden, easy-to-administer method for detecting AD risk.

Cross-sectional and longitudinal changes in mind-wandering in older adulthood.

Age-related declines in the frequency of mind-wandering are well established. Theories of mind-wandering have attempted to explain why this decline occurs, but no one theory firmly predicts such changes. One problem with these theoretical views, and the studies that have grown out of them, is their reliance on cross-sectional methods, which do not account for within-person changes over time in mind-wandering, and it is well-documented that cross-sectional and longitudinal changes in some cognitive domains do not align.

High-frequency assessment of mood, personality, and cognition in healthy younger, healthy older and adults with cognitive impairment.

Increased variability in cognitive scores, mood or personality traits can be indicative of underlying neurological disorders. Whether variability in cognition is due to changes in mood or personality is unknown. A total of 66 younger adults, 51 healthy older adults and 38 participants with cognitive impairment completed 21 daily sessions of attention, working memory, mood, and personality assessment.

Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers.

Introduction: Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers.

Methods: We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET.

A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests.

Cognition Mediates the Association Between Cerebrospinal Fluid Biomarkers of Amyloid and P-Tau and Neuropsychiatric Symptoms.

Background: Neuropsychiatric symptoms (NPS) can be an early manifestation of Alzheimer's disease (AD). However, the associations among NPS, cognition, and AD biomarkers across the disease spectrum are unclear.

Objective: We analyzed cross-sectional mediation pathways between cerebrospinal fluid (CSF) biomarkers of AD (Aβ1-42, p-tau181), cognitive function, and NPS.

The life-saving benefit of dexamethasone in severe COVID-19 is linked to a reversal of monocyte dysregulation.

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes.

Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial.

Importance: Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD).

Objective: To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment.

Design, Setting, And Participants: From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD.

Pick a PACC: Comparing domain-specific and general cognitive composites in Alzheimer disease research.

Objective: We aimed to illustrate how complex cognitive data can be used to create domain-specific and general cognitive composites relevant to Alzheimer disease research.

Method: Using equipercentile equating, we combined data from the Charles F. and Joanne Knight Alzheimer Disease Research Center that spanned multiple iterations of the Uniform Data Set.

Disease staging of Alzheimer's disease using a CSF-based biomarker model.

Biological staging of individuals with Alzheimer's disease (AD) may improve diagnostic and prognostic workup of dementia in clinical practice and the design of clinical trials. In this study, we used the Subtype and Stage Inference (SuStaIn) algorithm to establish a robust biological staging model for AD using cerebrospinal fluid (CSF) biomarkers. Our analysis involved 426 participants from BioFINDER-2 and was validated in 222 participants from the Knight Alzheimer Disease Research Center cohort.

Timing of Biomarker Changes in Sporadic Alzheimer's Disease in Estimated Years from Symptom Onset.

Objective: A clock relating amyloid positron emission tomography (PET) to time was used to estimate the timing of biomarker changes in sporadic Alzheimer disease (AD).

Methods: Research participants were included who underwent cerebrospinal fluid (CSF) collection within 2 years of amyloid PET. The ages at amyloid onset and AD symptom onset were estimated for each individual.

Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease.

Introduction: Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.

Methods: We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker.

Antecedents of mind wandering states in healthy aging and mild cognitive impairment.

Objective: Mind wandering refers to periods of internally directed attention and comprises up to 30% or more of our waking thoughts. Frequent mind wandering can be detrimental to ongoing task performance. We aim to determine whether rates of mind wandering change in healthy aging and mild cognitive impairment and how differences in mind wandering contribute to differences in attention and working memory.

Naturalistic assessment of reaction time variability in older adults at risk for Alzheimer's disease.

Objective: Maintaining attention underlies many aspects of cognition and becomes compromised early in neurodegenerative diseases like Alzheimer's disease (AD). The consistency of maintaining attention can be measured with reaction time (RT) variability. Previous work has focused on measuring such fluctuations during in-clinic testing, but recent developments in remote, smartphone-based cognitive assessments can allow one to test if these fluctuations in attention are evident in naturalistic settings and if they are sensitive to traditional clinical and cognitive markers of AD.

The pathophysiology of sepsis and precision-medicine-based immunotherapy.

Sepsis remains a major cause of morbidity and mortality in both low- and high-income countries. Antibiotic therapy and supportive care have significantly improved survival following sepsis in the twentieth century, but further progress has been challenging. Immunotherapy trials for sepsis, mainly aimed at suppressing the immune response, from the 1990s and 2000s, have largely failed, in part owing to unresolved patient heterogeneity in the underlying immune disbalance.

Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?

The use of biomarkers for the early detection of Alzheimer's disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.

Whole blood stimulation as a tool for studying the human immune system.

The human immune system is best accessible via tissues and organs not requiring major surgical intervention, such as blood. In many circumstances, circulating immune cells correlate with an individual's health state and give insight into physiological and pathophysiological processes. Stimulating whole blood ex vivo is a powerful tool to investigate immune responses.