Association of Alzheimer’s disease biomarkers with low premorbid intellectual functioning in a multi-ethnic community-dwelling cohort: A cross-sectional study of HABS-HD

Abstract

Background: Individuals with intellectual disability (ID) may have a five-fold increased risk for developing Alzheimer's disease (AD). However, studies investigating brain aging among individuals with ID without Down syndrome (DS) are lacking. To begin addressing this gap, our study utilized word reading, a widely recognized indicator of an individual's premorbid intellectual ability (pIQ), to examine the effects of ID without DS on plasma AD biomarker outcomes. Objective: To investigate the relationship between premorbid intellectual ability (pIQ) and plasma AD biomarkers in individuals with ID without DS, while considering ethnic differences in these associations. Methods: Participants from the Health & Aging Brain Study – Health Disparities (HABS-HD) were categorized into low (z ≤ −2.00) or average (z = 0.00 ± 1.00) pIQ groups based on word reading scores. Plasma biomarkers including Aβ₄₀, Aβ₄₂, Aβ_42/40, phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), and total tau (t-tau) were assayed using Simoa technology. Results: Individuals with low pIQ exhibited significantly higher levels of p-Tau181 (p < 0.05), NfL (p < 0.05), and t-tau (p < 0.05) compared to those with average pIQ. Stratified analysis by ethnicity revealed differential associations, with Hispanic and non-Hispanic White (NHW) participants showing distinct biomarker profiles relative to non-Hispanic Black (NHB) individuals. Conclusions: The findings demonstrate that low pIQ is a reliable factor associated with plasma AD biomarker outcomes. Ethnicity appears to modulate these associations, suggesting complex interactions between factors driving AD susceptibility across diverse populations. This study highlights the importance of considering both pIQ and ethnicity in neurodegenerative processes, particularly in individuals with non-DS intellectual developmental disability.