White matter hyperintensity burden mediates impact of vascular risk factors on cognitive impairment in SOL-INCA

Abstract

Introduction: HCHS/SOL is a representative study of Hispanic/Latinos living in the US. SOL-INCA examines cognition amongst those of HCHS/SOL over age 50 and SOL-INCA-MRI obtains quantitative MRI measures on a subgroup of these individuals. Prior research in SOL-INCA found that vascular risk factors summarized by the Framingham Cardiovascular Risk Score (Fram CVD) is associated with Mild Cognitive Impairment (MCI)1. We hypothesize that the extent of white matter hyperintensities (WMH) will partially mediate this impact of Fram CVD on MCI prevalence in this cohort. Methods: SOL-INCA-MRI consists of 2366 individuals of Hispanic/Latino Heritage from 4 centers across the US. Demographics of the cohort are summarized in the Table. High resolution MRI were acquired and WMH burden measured by previously reported methods2. WMH volumes were natural log transformed and corrected for scanner type using NeuroCombat. General linear models were used to test the associated between diagnosis (normal, questionable impairment and MCI) and Fram CVD and WMH adjusting for age, gender, education, heritage, and center. Casual mediation analysis was also performed to assess the extent to which WMH mediated the association between Fram CVD and diagnosis. Results: Subjects were 64.6 + 6.8 years of age at MRI, 68.5% were female, 16% had questionable impairment and 13% had MCI. Mean Fram CVD risk was 11.4 + 0.9%. Mean log WMH was -0.13 +1.55. Diagnosis was significantly associated with Fram CVD (beta= 780, p <0.0001) and WMH (beta =34, p <0.0001). Fram CVD was also strongly associated with WMH (beta = 2.6, p <0.0001). Causal mediation analysis found that WMH significantly mediated the association of Fram CVD to Diagnosis (p < 0.0001) by a proportion of 10%. Discussion: These results indicate that at least part of the impact of Fram CVD of MCI prevalence is mediated by the impact of Fram CVD on white matter injury suggesting that microvascular disease is a strong predictor of cognitive impairment amongst Hispanic/Latinos in the US.