Plasma amyloid beta biomarkers predict amyloid positivity and longitudinal clinical progression in mild cognitive impairment.

Introduction: Previous studies have examined the predictive accuracy of plasma amyloid beta (Aβ) biomarkers in clinical cohorts. However, their accuracy for predicting amyloid-positive patients in community-based cohorts is unclear. This study aimed to determine the predictive accuracy of Aβ precursor protein 669-711/Aβ1-42, Aβ1-40/1-42 and their composite biomarkers for brain amyloid deposition or the clinical progression in community-dwelling older adults with mild cognitive impairment (MCI).

Emerging Alzheimer's disease treatment paradigms: A late-stage clinical trial review.

Introduction: Without disease-modifying interventions, Medicare and Medicaid spending on Alzheimer's disease (AD) management is expected to reach 637 billion USD annually by 2050. The recent advent of promising AD therapies after decades of a near-total failure rate in clinical trials suggests that more disease-modifying therapies are on the horizon. In this review, we assess the late-stage pipeline of disease-modifying candidates for AD and offer a novel classification of intervention candidates by treatment paradigms-groups of candidates that share an underlying biological mechanism of action and general disease target.

Assessment of disease impact through health-related quality of life measurement in primary progressive aphasia.

Introduction: Measurements of health-related quality of life (HRQoL) are important for capturing disease impact beyond physical health and relative to other diseases but have rarely been assessed in primary progressive aphasia (PPA).

Methods: HRQoL was characterized overall, by sex and subtype in PPA ( = 118) using the Health Utilities Index-2/3 (HUI2/3). Multiple linear regression assessed associations between HRQoL and language severity.

Stress-related coping and its relationship to well-being in nursing assistants and personal care aides in nursing homes and assisted living.

Introduction: Professional caregivers (nursing assistants and personal care aides) in nursing homes (NH) and assisted living (AL) provide the majority of long-term residential care for persons with Alzheimer's disease and related dementias. Their work is stressful, but until recently, no measures were available to assess stress in this workforce. Using the new Long-Term Care Cope (LTC COPE) scale, this study evaluates the relationship of coping with staff demographic characteristics and outcomes; the findings can be used to develop and evaluate interventions to improve staff well-being.

Trends and determinants of choline alfoscerate use in newly diagnosed Alzheimer's disease patients in Korea.

Background: Choline alfoscerate, a cholinergic precursor, is widely used in Korea for dementia-related symptoms and is covered by national health insurance (NHI). This study investigates the utilization trends and factors influencing choline alfoscerate prescription in newly diagnosed Alzheimer's disease (AD) patients using real-world data.

Methods: We analyzed data from the Health Insurance Review and Assessment Service (HIRA) for patients aged 60 years and older who were newly diagnosed with AD between 2012 and 2019.

Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics.

Introduction: Alzheimer's disease is partially characterized by the progressive accumulation of aggregated tau-containing neurofibrillary tangles. Although the association between accumulated tau, neurodegeneration, and cognitive decline is critical for disease understanding and clinical trial design, we still lack robust tools to predict individualized trajectories of tau accumulation. Our objective was to assess whether brain imaging biomarkers of flortaucipir-positron emission tomography (PET), in combination with clinical and genomic measures, could predict future pathological tau accumulation.

Adaptive measurement of cognitive function based on multidimensional item response theory.

Introduction: Up to 20% of older adults in the United States have mild cognitive impairment (MCI), and about one-third of people with MCI are predicted to transition to Alzheimer's disease (AD) within 5 years. Standard cognitive assessments are long and require a trained technician to administer. We developed the first computerized adaptive test (CAT) based on multidimensional item response theory (MIRT) to more precisely, rapidly, and repeatedly assesses cognitive abilities across the adult lifespan.

The HOPE4MCI study: AGB101 treatment slows progression of entorhinal cortex atrophy in ε4 non-carriers with mild cognitive impairment due to Alzheimer's disease.

Introduction: Hippocampal hyperactivity is a hallmark of prodromal Alzheimer's disease (AD) that predicts progression in patients with amnestic mild cognitive impairment (aMCI). AGB101 is an extended-release formulation of levetiracetam in the dose range previously demonstrated to normalize hippocampal activity and improve cognitive performance in aMCI. The HOPE4MCI study was a 78-week trial to assess the progression of MCI due to AD.

Relationship between physical activity and biomarkers of pathology and neuroinflammation in preclinical autosomal-dominant Alzheimer's disease.

Objective: Physical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists.

Unlabelled: Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations.

Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Alzheimer's disease drug development in an evolving therapeutic landscape.

Unlabelled: The Alzheimer's disease (AD) research field has entered a new era, where our fundamental understanding of the pathophysiology of AD and advances in biomarkers have not only allowed for earlier, timely, and accurate detection and diagnosis of the disease, but that amyloid removal has been shown to be associated with signals of slowing cognitive and functional decline. Although recent FDA-approved amyloid plaque-lowering monoclonal antibody therapies have shifted the trajectory of AD, additional treatment options will be key to further slowing clinical decline or stopping disease progression. Thus, new and emerging therapies for AD have created an evolving therapeutic landscape.

An environmental scan of equity-related measures for the certified nursing assistant dementia care workforce.

Introduction: Certified nursing assistants (CNAs) constitute the largest segment of the nursing home workforce, with over 50% of the dementia care workforce comprised of racial and ethnic minoritized individuals. Despite their critical role in dementia care, CNAs face significant inequities in terms of salary, treatment, and working conditions. To enhance equity and improve working conditions, valid and reliable measures are essential for nursing homes to assess their current environment, track progress, and refine strategies.

Designing and implementing the IDEAL Study: A randomized clinical trial of genotype disclosure for late-onset Alzheimer's disease in an urban Latino population.

Introduction: The (IDEAL) Study is a randomized clinical trial investigating the psychosocial, behavioral, and cognitive impacts of apolipoprotein E () genotype disclosure for late-onset Alzheimer's disease (AD) among Latinos.

Methods: We used address-based sampling to recruit English- and Spanish-speaking Latinos aged 40-64 living in northern Manhattan for a community-based Baseline Survey about their knowledge and opinions about AD. Participants eligible for the clinical trial were invited to complete an Introductory Session, including AD and genetics education and informed consent, before undergoing genotyping for .

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Geometric series exists in nature: Evidence from sorted area sequences of floral parts and leaves.

The concept of a geometric series (GS) plays an important role in mathematics. However, it has been neglected in describing biological size series. Herein, we show that a GS describes the nonreproductive (perianth) parts of the flowers of four Magnoliaceae species and two Rosaceae species and the leaves of 60 Alangium chinense and 60 Shibataea chinensis shoots.

Retinal Müller Cell-Released Exosomal MiR-92a-3p Delivers Interleukin-17A Signal by Targeting Notch-1 to Promote Diabetic Retinopathy.

Purpose: Inflammatory processes have been involved in diabetic retinopathy (DR). Interleukin (IL)-17A, a pro-inflammatory cytokine, is associated with DR occurrence and development. However, mechanisms underlying the IL-17A impact on DR need further investigations.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

INSIHGT: an accessible multi-scale, multi-modal 3D spatial biology platform.

Biological systems are complex, encompassing intertwined spatial, molecular and functional features. However, methodological constraints limit the completeness of information that can be extracted. Here, we report the development of INSIHGT, a non-destructive, accessible three-dimensional (3D) spatial biology method utilizing superchaotropes and host-guest chemistry to achieve homogeneous, deep penetration of macromolecular probes up to centimeter scales, providing reliable semi-quantitative signals throughout the tissue volume.

In vivo imaging of glycogen in human muscle.

Probing regional glycogen metabolism in humans non-invasively has been challenging due to a lack of sensitive approaches. Here we studied human muscle glycogen dynamics post-exercise with a spatial resolution of millimeters and temporal resolution of minutes, using relayed nuclear Overhauser effect (glycoNOE) MRI. Data at 5T showed a homogeneous distribution of glycogen in resting muscle, with an average concentration of 99 ± 13 mM.

Improved Adherence to Lipid Screening in the Pediatric Cardiology Clinic: A Quality Improvement Project.

Introduction: Lipid screening identifies at-risk patients to facilitate cardiovascular risk reduction. National pediatric guidelines recommend universal lipid screening between 9-11 and 17-21 years of age. We aimed to improve adherence to lipid screening for all age-appropriate outpatient pediatric cardiology visits from a baseline of 35% to 90% between November 2021 and July 2023.

Increasing Premedication for Neonatal Intubation: A Quality Improvement Initiative.

Introduction: Endotracheal intubation is frequent in the neonatal intensive care unit (NICU) but may result in neonatal distress and instability. Premedication reduces adverse effects, such as hypoxia, bradycardia, and pain. The Specific, Measurable, Achievable, Relevant and Time-Bound aim for this project was to increase premedication use for nonemergent neonatal intubation in a specific NICU from 22% to 80% from March 2021 to May 2023.

The rhythm of horse gaits.

What makes animal gaits so audibly rhythmic? To answer this question, we recorded the footfall sound of 19 horses and quantified the rhythmic differences in the temporal structure of three natural gaits: walk, trot, and canter. Our analyses show that each gait displays a strikingly specific rhythmic pattern and that all gaits are organized according to small-integer ratios, those found when adjacent temporal intervals are related by a mathematically simple relationship of integer numbers. Walk and trot exhibit an isochronous structure (1:1)-similar to a ticking clock-while canter is characterized by three small-integer ratios (1:1, 1:2, 2:1).

Macular patterns of neuronal and visual field loss in recovered optic neuritis identified by machine learning.

We used machine learning to investigate the residual visual field (VF) deficits and macula retinal ganglion cell (RGC) thickness loss patterns in recovered optic neuritis (ON). We applied archetypal analysis (AA) to 377 same-day pairings of 10-2 VF and optical coherence tomography (OCT) macula images from 93 ON eyes and 70 normal fellow eyes ≥ 90 days after acute ON. We correlated archetype (AT) weights (total weight = 100%) of VFs and total retinal thickness (TRT), inner retinal thickness (IRT), and macular ganglion cell-inner plexiform layer (GCIPL) thickness.