Prognostic Value of Plasma Glial Fibrillary Acidic Protein in Cognitively Unimpaired Older Adults: Results from the A4 Study.

Introduction: Plasma glial fibrillary acidic protein (GFAP), a marker of astrocytic activation, has been linked to Alzheimer's disease; however, its prognostic value in cognitively unimpaired (CU) individuals remains unclear.

Methods: We included 949 CU older adults from the A4 preclinical AD trial, and its companion LEARN cohort. Baseline plasma GFAP was measured, and longitudinal associations with cognitive decline, clinical dementia rating (CDR) progression, and imaging biomarkers were assessed over 240 weeks.

Late-life emergence of neuropsychiatric symptoms and risk of cognitive impairment in cognitively unimpaired individuals.

Introduction: Neuropsychiatric symptoms (NPS) often precede cognitive impairment. We investigated the longitudinal relationship between emergent, significant NPS and cognitive decline in cognitively unimpaired older adults. We also assessed the combined effect of NPS and Alzheimer's disease (AD) biomarkers on subsequent cognitive impairment.

Racial and ethnic differences in plasma p-tau217 ratio biomarker eligibility rates in a preclinical AD trial with lecanemab.

Introduction: Consistent predictive performance across racial and ethnic groups is essential to the use of plasma biomarkers as screening tools in preclinical Alzheimer's disease trials.

Methods: Logistic regression examined racial and ethnic group differences in plasma eligibility using an algorithm that included Phosphorylated tau217 to non-phosphorylated tau217 ratio, amyloid beta 42/40, age, and apolipoprotein E to predict > 18 Centiloids on amyloid imaging in cognitively unimpaired individuals.

Results: Among 6437 participants screened, with non-Hispanic (NH) White as the reference group, odds ratios of plasma ineligibility were 2.

Alzheimer's Disease Research Center Down Syndrome Cores: Experience from two sites.

Down syndrome (DS) is the most common genetic cause of Alzheimer's disease (AD). As individuals with DS live longer, the prevalence of AD-related dementia increases, underscoring a growing public health concern. Historically, research efforts have largely overlooked the early manifestations and neuropathological trajectory of AD in DS, limiting our understanding of how closely it mirrors or diverges from sporadic AD in the general population.

Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia-specific perspectives.

The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease-modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment-induced changes in disease biology. These frameworks enable opportunities for personalized interventions-encompassing pharmacological and non-pharmacological strategies-and for enhanced clinical trial design.

Effectiveness of a local recruitment registry in older adults in Southern California.

Background: Despite their potential as tools for improving the efficiency of accrual in clinical research, few analyses have assessed the effectiveness of recruitment registries. We investigated referrals to clinical research studies from the University of California, Irvine Consent-to-Contact registry, a local online recruitment registry in Orange County, CA. Our analyses sought to quantify the total number of referrals and the proportion of referrals leading to subsequent enrollment in a clinical research study.

Five years of the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD).

Background: First held in 2020, the Institute on Methods and Protocols for Advancement of Clinical Trials in ADRD (IMPACT-AD) is a program to train the next generation of Alzheimer's disease (AD) and related dementias (AD/ADRD) clinical trialists.

Methods: IMPACT-AD includes didactic, workshop, and small group components.

Results: IMPACT-AD has trained 18 alumni-scholars (accepted from 424 applicants), of whom 67% were female.

It is time to share Alzheimer biomarker results in dementia with Lewy bodies.

Unlabelled: There are increasing calls for sharing individual biomarker results with participants in dementia research. No studies investigate returning Alzheimer's disease (AD) biomarker results to individuals with syndromic dementia with Lewy bodies (DLB) even though most of these individuals have both pathologies. This perspective argues that AD biomarkers are valid, interpretable, and actionable, particularly relating to expected prognosis and treatment effects, in people with DLB.

Understanding participants' attitudes toward research in the CARE registry.

Introduction: Elucidating barriers and facilitators to research participation is especially important in Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations, who are significantly underrepresented in Alzheimer's disease and related dementias (ADRD) research.

Methods: We analyzed multilingual data from the 7-item Research Attitude Questionnaire (RAQ) among diverse AANHPI participants across a broad age range in the Collaborative Approach for AANHPI Research and Education (CARE) registry.

Results: Upon enrollment, 10,063 CARE participants were invited to complete the RAQ; 72.

Estimating the optimal cutoff for the IGT-AD Distress subscale adapted for amyloid PET results disclosure.

Introduction: Research on diagnostic and biomarker disclosure has significantly increased, particularly in the field of Alzheimer's disease (AD). The psychological impact of learning amyloid positron emission tomography (PET) results has been frequently assessed using the Impact of Genetic Testing for Alzheimer's Disease (IGT-AD) instrument. Establishing an optimal cutoff score for this screening tool is essential for efficiently identifying individuals who may require psychological support after amyloid PET disclosure.

Association of Alzheimer's disease concerns with amyloid burden and lifestyle behaviors in cognitively unimpaired older adults.

Introduction: The extent to which Alzheimer's disease (AD) concerns relate to pathological changes in cognitively unimpaired populations is unclear.

Methods: We analyzed screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study to determine if AD concerns are associated with amyloid burden in cognitively unimpaired older adults, and how they relate to lifestyle. AD concerns were measured using the six-item Concerns about Alzheimer's Disease Questionnaire.

Virtual Data Collection Strategies in Research on Alzheimer's Disease and Related Dementias (ADRD).

Background And Objectives: Remote data collection emerged as a valuable method for engaging vulnerable populations, such as individuals participating in Alzheimer's disease and related dementias (ADRD) research. Despite challenges like technology readiness and privacy concerns, remote methods have the potential to enhance participation among diverse groups by offering flexibility while addressing accessibility barriers such as geographic distance. This study shares experiences with virtual data collection and the strategies employed to enhance ADRD research involving individuals with and at risk of cognitive impairment.

Increasing representation of Asian American, Native Hawaiian, and Pacific Islander communities in aging, dementia, and caregiving research: An update from the CARE registry.

Introduction: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) communities are among the fastest growing segments of older adults in the United States yet remain underrepresented in aging, dementia, and caregiving research.

Methods: The Collaborative Approach for AANHPI Research & Education (CARE), a recruitment registry, aims to improve the representation of AANHPI older adults in research. We describe activity to date, as well as planned expansions in cultural groups, language capacity, and data collection in the registry.

Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer's disease.

Background: Nicotinamide, a form of B3 vitamin, is an NAD precursor that reduces pTau levels via histone deacetylase inhibition in murine models of Alzheimer's disease (AD). A recent phase 2a randomized placebo-controlled trial tested high-dose oral nicotinamide for the treatment of early AD. While nicotinamide demonstrated good safety and tolerability, it did not significantly lower CSF pTau, the primary biomarker endpoint of the study.

Impact of study partner replacement in a mild cognitive impairment clinical trial.

Background: In Alzheimer's disease (AD) clinical trials, including trials enrolling patients with mild cognitive impairment (MCI), participants must enroll with a study partner (SP). SPs ensure compliance and are a source of study data, including assessments of the participant's cognition and function. Consistency in SP reporting is essential to trial data integrity.

Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer's disease: the need for rigor.

We consider the recent publication by Ornish and colleagues and the rigor expected for interventional clinical trials. We contend that lifestyle intervention trials should strive for the same rigor as drug trials and highlight opportunities to improve rigor in this example, particularly in design, data analysis, and publication of results for this and other lifestyle intervention studies.

Research Attitudes Questionnaire scores and retention in a recruitment registry.

Background: Recruitment registries are maximally effective when registrants are retained to the point of referral. The Research Attitudes Questionnaire (RAQ) has previously been shown to predict research participation behaviors, including Alzheimer's disease clinical trial completion.

Objective: To test the hypothesis that RAQ score is associated with retention behaviors in a local recruitment registry.

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.

Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.

Background And Objectives: Nicotinamide is a coenzyme involved in cellular oxidation-reduction reactions that can inhibit Class III histone deacetylases (HDACs) or sirtuins. HDAC inhibition can affect numerous therapeutic pathways, including tau phosphorylation. We tested the hypothesis that nicotinamide treatment could reduce tau phosphorylation in early Alzheimer disease (AD).

Alzheimer's disease biomarkers and the tyranny of treatment.

Advances in treatment are changing not only the therapeutic options for patients with Alzheimer's disease; they're also changing their diagnostic options. Technologies to detect amyloid such as PET imaging and blood or CSF testing now have a central role in Alzheimer's disease care. Notably, this role has been made possible by regulatory approval and coverage by payers of therapies.