Public Health.

Background: In the United States, Latino communities are disproportionately impacted by Alzheimer's disease and related dementias (ADRDs) with 11.1% and 5.3% living with mild cognitive impairment and mild dementia due to ADRDs, respectively.

Public Health.

Background: Scalable, efficient methods are needed to enroll diverse populations of older adults into AD observational studies and clinical trials. We evaluated preliminary feasibility of a novel, digital, culturally informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4).

Methods: Digital advertising tailored towards Black/African American and Latinx older adults residing near six clinical ADNI sites directed potential participants to a recruitment website (Figure 1).

The ADNI4 Digital Study: A novel approach to recruitment, screening, and assessment of participants for AD clinical research.

Introduction: We evaluated preliminary feasibility of a digital, culturally-informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4).

Methods: Participants were recruited using digital advertising and completed digital surveys (e.g.

The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB).

The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond.

Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4.

Introduction: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022.

Increasing the Cognitive Screening Efficiency of Global Phase III Trials in Early Alzheimer Disease: The Cognitive Task Force.

Purpose: A Cognitive Task Force (CTF) was established for the MissionAD program with the aim of reducing the screen failure (SF) rate to ∼30% and thereby reduce unnecessary subject burden, site burden, and excess trial costs.

Methods/subjects: The MissionAD program consisted of 2 global phase 3 studies evaluating the BACE inhibitor elenbecestat in subjects with early Alzheimer disease. The CTF monitored and engaged with MissionAD clinical sites to provide support through collegial discussions to maximize the efficiency of the preconsent recruitment phase.

Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination.

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign.

Pilot Evaluation of the Unsupervised, At-Home Cogstate Brief Battery in ADNI-2.

Background: There is a need for feasible, scalable assessments to detect cognitive impairment and decline. The Cogstate Brief Battery (CBB) is validated for Alzheimer's disease (AD) and in unsupervised and bring your own device contexts. The CBB has shown usability for self-completion in the home but has not been employed in this way in a multisite clinical trial in AD.

The β-Secretase BACE1 in Alzheimer's Disease.

BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) was initially cloned and characterized in 1999. It is required for the generation of all monomeric forms of amyloid-β (Aβ), including Aβ, which aggregates into bioactive conformational species and likely initiates toxicity in Alzheimer's disease (AD). BACE1 concentrations and rates of activity are increased in AD brains and body fluids, thereby supporting the hypothesis that BACE1 plays a critical role in AD pathophysiology.

Recommended cognitive outcomes in preclinical Alzheimer's disease: Consensus statement from the European Prevention of Alzheimer's Dementia project.

The Horizon 2020/IMI European Prevention of Alzheimer's Dementia (EPAD) project will undertake large-scale proof-of-concept trials in predementia Alzheimer's disease (AD). Within EPAD, the monitoring of cognitive trajectories in the preclinical period will constitute a central outcome measure; however, there are currently no clear guidelines as to how this should be achieved as most measures have been developed for the period around dementia diagnosis. The EPAD Scientific Advisory Group for Clinical and Cognitive Outcomes identified appropriate cognitive measures based on a literature search covering both cognitive correlates of preclinical brain changes from imaging studies and cognitive changes observed over time in nondementia population cohorts developing incident dementia.

Detecting cognitive changes in preclinical Alzheimer's disease: A review of its feasibility.

Significant progress has been made in characterizing the biological changes occurring in preclinical Alzheimer's disease (AD). Cognitive dysfunction has been viewed, however, as a late-stage phenomenon, despite increasing evidence that changes may be detected in the decades preceding dementia. In the absence of comprehensive evidence-based guidelines for preclinical cognitive assessment, longitudinal cohort and neuroimaging studies have been reviewed to determine the temporal order and brain biomarker correlates of specific cognitive functions.

Prolonged pharmacodynamic effects of S-0139, an intravenously administered endothelin A (ET) antagonist, in the human forearm blood flow model.

Aims: To estimate the pharmacologically active dose range of a new investigational compound S-0139, a selective endothelin A (ET(A)) receptor antagonist, in man, and to examine the duration of its pharmacodynamic effect.

Methods: Venous occlusion plethysmography was performed to assess changes in forearm blood flow following intra-brachial administration of endothelin-1 (ET-1). ET(A) antagonists have been shown to block ET-1-induced vasoconstriction in this model.

Synergistic effect of an endothelin type A receptor antagonist, S-0139, with rtPA on the neuroprotection after embolic stroke.

Background And Purpose: Using a model of embolic stroke, the present study tested the hypothesis that blockage of endothelin-1 with S-0139, a specific endothelin type A receptor (ET(A)) antagonist, enhances the neuroprotective effect of recombinant tissue plasminogen activator (rtPA) by suppressing molecules that mediate thrombosis and blood brain barrier (BBB) disruption induced by ischemia and rtPA.

Methods: Rats (n=104) subjected to embolic middle cerebral artery (MCA) occlusion were randomly divided into 1 of 4 infusion groups with 26 rats per group: (1) the control group in which rats were administered saline, (2) the monotherapy rtPA group in which rtPA was intravenously administered at a dose of 10 mg/kg 4 hours after MCA occlusion, (3) the monotherapy S-0139 group in which S-0139 was intravenously given 2 hours after MCA occlusion, and (4) the combination of rtPA +S-0139 group in which S-0139 and rtPA were given 2 and 4 hours after MCA occlusion, respectively. Measurements of infarct volume and parenchymal hemorrhage, behavioral outcome, and immunostaining were performed on rats euthanized 1 and 7 days after stroke.