Biomarker Evaluation in Young Onset Dementia from Diverse Populations (BEYONDD)

ABSTRACT / PROJECT SUMMARY Early onset dementia (EOD) is devastating because it affects individuals at a time of life when they have peak personal and professional responsibilities and are actively contributing to society. Previous work has identified Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) as the most common causes of EOD.

Despite this, most studies of EOD primarily have recruited non-Latinx Whites (NLW). Black and Latinx adults bear a disparate and disproportionate burden of biological and sociocultural vulnerabilities that confer increased ADRD risk in older persons, but the etiologies of dementia in younger members of these Diverse Populations

(DPs) are not well understood. Dedicated and well-resourced efforts specifically tailored to study EOD in DPs, including identification of unique risk and resilience factors, are urgently needed. Plasma biomarkers of amyloid, tau and neurodegeneration and remotely collected automated clinical and cognitive assessments could greatly

reduce barriers to characterization of EOD in DPs, but most studies evaluating these technologies have been conducted in older NLW. The Biomarker Evaluation in Young Onset Dementia from Diverse Populations (BEYONDD) longitudinal study will address these gaps in knowledge. This five-year longitudinal study will

implement a scalable, intensive, and culturally-informed community-engaged research approach to remotely enroll 2,000 adults (<65yrs with 70% DPs and 30% NLW; n=1,700 with cognitive or behavioral impairments [CBI] & n=300 healthy controls) who will complete baseline automated cognitive, clinical, and sociocultural assessments, and blood draws for plasma biomarkers (Aβ42/40, P-tau217 and NfL) in the community, followed by either in-person (n=1,000 with CBI & n=300 healthy controls) or remote (n = 700) longitudinal evaluations. The annual in-person evaluations include “gold standard” clinical evaluations for etiologic diagnosis performed by expert clinicians including neuroimaging evaluations (MRI and amyloid PET). The annual remote evaluations will rely on automated tools. The study aims to: (1) Compare the etiology, severity, and cognitive and biomarker (plasma biomarkers and amyloid PET) profiles of EOD across ethnocultural groups (Black, Latinx and NLW); (2) Examine the effects of biological, psychological and sociocultural factors on EOD and resilience (resistance to EOD despite biological risk) outcomes across ethnocultural strata; (3) Validate plasma biomarkers and cognitive markers collected in the community by comparing the diagnostic accuracy of plasma Aβ42/40, P-tau217, and NfL versus “gold standard” clinical diagnosis and neuro-imaging biomarkers across ethnocultural groups, and evaluating the added value of remote cognitive assessments and clinical metabolic tests to plasma biomarkers’ diagnostic accuracy. Eligible participants will be co-enrolled in ongoing longitudinal ADRD studies focused on EOD while the rest will return for longitudinal assessments through BEYONDD. This project brings together a diverse team of leading scientists in EOD and brain health disparities, private and public stakeholders, and diverse community-based partner organizations, to create new resources to promote inclusive research in EOD.