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.

The utility of recruitment incentives in early Alzheimer's disease trials.

Introduction: Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development.

Methods: We performed a conjoint experiment to compare preferences among 26 patients with mild cognitive impairment for four trial features including designs incorporating active aducanumab-control (vs. placebo), returning tau positron emission tomography (PET) results (vs.

Reasons for undergoing amyloid imaging among diverse enrollees in the A4 study.

Introduction: Understanding attitudes toward participation among diverse preclinical Alzheimer's disease (AD) trial participants could yield insights to instruct future recruitment.

Methods: Using data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) Study, we examined differences among mutually exclusive racial and ethnic groups in views and perceptions of amyloid imaging (VPAI), a measure of motivations to undergo amyloid biomarker testing in the setting of preclinical AD. We used linear regression to quantify differences at baseline.

Effect of gamification with a support partner to increase physical activity in older adults at risk for Alzheimer's disease: The STEP 4Life randomized clinical trial.

Introduction: Physical activity is associated with reduced risk of cognitive and functional decline but scalable, sustainable interventions for populations at risk for Alzheimer's disease (AD) and AD and related dementias (ADRD) are lacking.

Methods: A 12-week randomized-controlled trial was conducted with a 3-week follow-up using a national AD prevention registry (GeneMatch). The control group (n = 50) set step goals and received daily feedback.

Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial.

Introduction: In trials of amyloid-lowering drugs for Alzheimer's disease (AD), differential eligibility may contribute to under-inclusion of racial and ethnic underrepresented groups. We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659).

Methods: Univariate logistic regression models were used to examine group differences in plasma and PET amyloid screening eligibility.

Immediate Reactions to Alzheimer Biomarker Disclosure in Cognitively Unimpaired Individuals in a Global Truncated Randomized Trial.

Background And Objectives: Preclinical Alzheimer disease (AD) trials simultaneously test candidate treatments and the implications of disclosing biomarker information to cognitively unimpaired individuals.

Methods: The EARLY trial was a randomized, double-blind, placebo-controlled, phase 2b/3 study conducted in 143 centers across 14 countries from November 2015 to December 2018 after being stopped prematurely because of treatment-related hepatotoxicity. Participants age 60-85 years deemed cognitively unimpaired were disclosed an elevated or not elevated brain amyloid result by a certified clinician.

Study Partner Type and Adverse Event Reporting in Mild-to-Moderate Alzheimer's Disease Clinical Trials.

Background: In randomized clinical trials (RCTs), monitoring adverse events (AEs) and serious AEs (SAEs) is critical. All Alzheimer's disease (AD) RCTs require participants to enroll with a study partner.

Objective: We examined AE reporting rates in mild-to-moderate AD trials and their associations with study partner type.

Vietnamese American Perspectives on Engagement in an Aging-Focused Research Registry.

Introduction: We elicited Vietnamese Americans' perspectives on culturally appropriate recruitment into a new research registry: Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs) Research and Education (CARE).

Methods: Three focus groups were conducted with 21 Vietnamese Americans. Topics included knowledge about and experiences with research, outreach and recruitment methods for research participation and registry enrollment, and views about research incentives.

Post-disclosure distress among racial and ethnic groups in a preclinical AD trial.

Introduction: Trialists need a thorough understanding of whether reactions to Alzheimer's disease (AD) biomarker information differ among racial and ethnic groups in preclinical AD trials.

Methods: We used data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease Study to analyze cognitively unimpaired participants' responses on the Impact of Event Scale (IES) 24 to 72 hours after amyloid disclosure. We fit a linear regression model to test whether mean IES scores differed among participants from specific racial and ethnic groups.

Apolipoprotein E Genetic Testing in a New Age of Alzheimer Disease Clinical Practice.

The recent FDA approval of amyloid-lowering drugs is changing the landscape of Alzheimer disease (AD) clinical practice. Previously, genetic testing was not recommended in the care of people with AD because of limited clinical utility. With the advent of amyloid-lowering drugs, genotype will play an important role in guiding treatment recommendations.

Effects of informant replacement in Alzheimer's disease clinical trials.

Introduction: Alzheimer's disease (AD) trials require enrollment with an informant.

Methods: We assessed relationships between informant replacement and Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores across four AD trials. Using generalized estimating equations, we examined associations between replacement and change in ADCS-ADL between successive visits.

Retention of American Indian and Alaska Native participants in the National Alzheimer's Coordinating Center Uniform Data Set.

Introduction: The number of American Indian and Alaska Native (AI/AN) elders is expected to double by 2060. Thus it is imperative to retain AI/AN participants in longitudinal research studies to identify novel risk factors and potential targets for intervention for Alzheimer's disease and related dementias in these communities.

Methods: The National Alzheimer's Coordinating Center houses uniformly collected longitudinal data from the network of National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADRCs).

Estimating attrition in mild-to-moderate Alzheimer's disease and mild cognitive impairment clinical trials.

Background: Participant retention is a key factor that affects clinical trial integrity. Trial protocols estimate attrition as a function of sample size calculations. Alzheimer's disease (AD) is an area of active treatment development.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

Background: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression.

Methods: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated.

Biomarker disclosure protocols in prodromal Alzheimer's disease clinical trials.

Introduction: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker "screening" criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown.

Methods: We reviewed the literature to identify prodromal AD trials published in the past 10 years.

Research Attitude and Interest among Cancer Survivors with or without Cognitive Impairment.

Background: We examined the research attitudes and willingness to participate in clinical research among cancer survivors with varying degrees of cognitive function.

Methods: This is a secondary analysis of data collected through the University of California Irvine Consent-to-Contact registry. Cancer survivors completed the Cognitive Function Instrument (CFI), the Research Attitudes Questionnaire (RAQ), and willingness to participate (WTP) in certain research procedures.

Examining Utilization of Formal Supports and Related Impacts on Overall Well-Being Among East Asian American Family Caregivers of Persons With Dementia: A Mixed-Methods Study.

Background And Objectives: Although East Asian American family caregivers are known to underutilize formal support services, there is a lack of evidence regarding the associations of formal service utilization with caregivers' well-being. This study examined the prevalence of different types of home-and community-based formal service utilization among Korean and Chinese American family caregivers of persons with dementia and how utilization of such services was associated with their well-being. We also explored their overall experience in accessing and utilizing formal dementia support services and programs.

Frameworks for estimating causal effects in observational settings: comparing confounder adjustment and instrumental variables.

To estimate causal effects, analysts performing observational studies in health settings utilize several strategies to mitigate bias due to confounding by indication. There are two broad classes of approaches for these purposes: use of confounders and instrumental variables (IVs). Because such approaches are largely characterized by untestable assumptions, analysts must operate under an indefinite paradigm that these methods will work imperfectly.