The problem of multiple adjustments in the assessment of minimal clinically important differences.

Introduction: Anthropometric, demographic, genetic, and clinical features may affect cognitive, behavioral, and functional decline, while clinical trials seldom consider minimal clinically important differences (MCIDs) in their analyses.

Methods: MCIDs were reviewed taking into account features that may affect cognitive, behavioral, or functional decline in clinical trials of new disease-modifying therapies.

Results: The higher the number of comparisons of different confounders in statistical analyses, the lower values will be significant.

Cost-effectiveness of a multicomponent intervention against cognitive decline.

Introduction: The societal costs of dementia and cognitive decline are substantial and likely to increase during the next decades due to the increasing number of people in older age groups. The aim of this multicenter cluster-randomized controlled trial was to assess the cost-effectiveness of a multi-domain intervention to prevent cognitive decline in older people who are at risk for dementia.

Methods: We used data from a multi-centric, two-armed, cluster-randomized controlled trial ( trial, ID: DRKS00013555).

Association of corneal endothelial cell morphology with neurodegeneration in mild cognitive impairment and dementia.

Introduction: Corneal confocal microscopy (CCM) detects neurodegeneration in mild cognitive impairment (MCI) and dementia and identifies subjects with MCI who develop dementia. This study assessed whether abnormalities in corneal endothelial cell (CEC) morphology are related to corneal nerve morphology, brain volumetry, cerebral ischemia, and cognitive impairment in MCI and dementia.

Methods: Participants with no cognitive impairment (NCI), MCI, and dementia underwent CCM to quantify corneal endothelial cell density (CECD) and area (CECA), corneal nerve fiber morphology, magnetic resonance imaging (MRI) brain volumetry, and severity of brain ischemia.

Adhesion properties of polyimide coated stacks: An in-depth analysis of the cross-sectional nanoindentation method.

Adhesion at the interface between dissimilar materials in the semiconductor industry is an important topic, but reliable quantitative methods for strongly adhesive or highly plastic layers are hardly available. This study aims to investigate the suitability of the cross-sectional nanoindentation (CSN) method for determination of the critical energy release rate of thin film stacks in the presence of a polyimide layer as a representative structure for such a case. For this purpose, the adhesion of a deliberately weakened Si/SiO interface in a Si/SiO/Al/SiN/polyimide stack is examined by systematic variation of the experimental parameters.

Correlating disordered activation domain ensembles with gene expression levels.

Transcription factor proteins bind to specific DNA promoter sequences and initiate gene transcription. These proteins often contain intrinsically disordered activation domains (ADs) that regulate their transcriptional activity. Like other disordered protein regions, ADs do not have a fixed three-dimensional structure and instead exist in an ensemble of conformations.

Audio-visual concert performances synchronize audience's heart rates.

People enjoy engaging with music. Live music concerts provide an excellent option to investigate real-world music experiences, and at the same time, use neurophysiological synchrony to assess dynamic engagement. In the current study, we assessed engagement in a live concert setting using synchrony of cardiorespiratory measures, comparing inter-subject, stimulus-response, correlation, and phase coherence.

Site-level factors affecting nursing home implementation of a personalized music intervention: Qualitative analyses from Music & Memory: A Pragmatic Trial for Nursing Home Residents with Alzheimer's Disease (METRIcAL).

Background: Non-pharmacological interventions (NPIs) are preferred alternatives to using antipsychotic medications to manage disruptive behaviors in nursing home (NH) residents living with dementia. However, the implementation of these interventions is often complex in the NH environment. In this qualitative analysis of data from an embedded pragmatic clinical trial (ePCT) of a personalized music intervention, we describe NH-level implementation barriers and facilitators.

The association of dementia risk symptoms and functional activity in adults with Down syndrome.

Introduction: Adults with Down syndrome (DS) have an increased risk of Alzheimer's disease (AD) dementia, often showing neuropathological indicators by age 40. Physical function and activities of daily living (ADLs) are understudied areas of function that may inform dementia risk. We investigated associations among age, physical function (gait/balance, grip strength, and lower extremity strength), ADLs, and dementia risk symptoms in adults with DS.

Impacts of informant replacement in two industry-sponsored Alzheimer's disease clinical trials.

Introduction: In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who completes validated study instruments. We hypothesized that mid-trial informant replacement impacts study data in industry-sponsored trials.

Methods: We conducted a retrospective analysis of two industry-sponsored AD clinical trials testing semagacestat in mild-to-moderate AD dementia.

Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer's disease.

Introduction: The aggregation and spread of hyperphosphorylated, pathological tau in the human brain is hypothesized to play a key role in Alzheimer's disease (AD) as well as other neurogenerative tauopathies. O-GlcNAcylation, an important post-translational modification of tau and many other proteins, is significantly decreased in brain tissue of AD patients relative to healthy controls. Increased tau O-GlcNAcylation has been shown to reduce tau pathology in mouse in vivo tauopathy models.

A new measure of professional caregiver coping in long-term care: The LTC COPE.

Introduction: The professional caregiver workforce (nursing assistants and personal care aides) is critical to quality of care and quality of life in nursing home (NH) and assisted living (AL) settings. The work is highly stressful, so improving responses to stress in this workforce could contribute to satisfaction and retention. This research developed a coping measure appropriate for the diverse professional caregiver workforce.

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 .