Plasma A42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA-FAIM cohort

Introduction: It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (A beta)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults.Methods: Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma A beta 42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma A beta 42/40.Results: IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma A beta 42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low A beta 42/40 was associated with faster cognitive declines over time.Discussion: Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.