Effects of structural and social determinants of health and comorbidities on ethno‐racial differences in ATN plasma biomarkers of Alzheimer’s disease: A HABS‐HD study

Abstract

AbstractBackgroundEthno‐racial differences are observed in amyloid (A), tau (T), and neurodegeneration (N) plasma biomarkers of Alzheimer’s disease (AD). In neuroimaging studies, structural and social determinant of health (SSDOH) factors and associated health outcomes may mediate observed racial differences in neurodegeneration markers. However, little is known regarding the potential effects of SSDOH and downstream comorbidities on ethno‐racial differences in AT(N) plasma biomarkers. This study A) assessed potential differences in plasma Aβ42, Aβ40, Aβ42/40, t‐tau, and NfL among Mexican Americans (MA), non‐Hispanic Blacks (NHB), and non‐Hispanic Whites (NHW); B) determined whether SSDOH and comorbidity factors mediate potential ethno‐racial differences in AD plasma biomarkers.MethodData were obtained from the diverse and well‐characterized Health and Aging Brain Study – Health Disparities (HABS‐HD) and included MAs (n = 931), NHBs (n = 258), and NHWs (n = 942). Group differences in AT(N) plasma biomarkers were assessed using analysis of covariance. Age, sex, and cognitive status (Clinical Dementia Rating Scale Sum of Boxes) were included as covariates. Two multiple mediation models were performed with SSDOH (acculturation, chronic stress, income, area deprivation index) and comorbidity factors (body mass index [BMI], blood pressure, diabetes history) as the potential mediators, respectively. Models accounted for age, sex, and cognitive status, assumed nonlinear relationships, and allowed for mediators to be considered simultaneously.ResultPlasma Aβ42 was significantly lower in MAs compared to NHWs (p<0.05). Plasma NfL was significantly higher in MAs compared to NHBs (p<0.01) and for NHWs compared to NHBs (p<0.05). No other significant differences in plasma variables were observed (p’s>0.05). Group differences in plasma Aβ42 were mediated by comorbidity factors (BMI and history of diabetes), but not SSDOH. MAs had greater BMIs and history of diabetes compared to NHWs, both of which were associated with lower plasma Aβ42 levels. SSDOH and comorbidity factors did not mediate group differences in plasma NfL.ConclusionUsing a large and diverse community‐based cohort, we demonstrate that ethno‐racial differences in AD‐specific plasma biomarkers are, in part, due to modifiable health and comorbidity factors. This work informs the conditions that give rise to ethno‐racial differences in plasma ATN biomarkers while highlighting potential ethno‐racial disparities in AD research.