Vascular and metabolic profiles related to white matter hyperintensities in a multiethnic cohort from the HABS-HD study




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Purpose: There are more than 6 million people living with Alzheimer’s disease (AD) in the United States. Mexican-Americans (MA) and African-Americans (AA) are disproportionally affected by AD and related dementias, and it is expected that these disparities will increase in the coming years. AD commonly presents with vascular dementia and research has shown the relationship between the two to be complex, with many individuals presenting with mixed dementia. Vascular dementia is commonly related to small vessel disease. Small vessel disease occurs when endothelial damage in cerebrovascular circulation causes ischemia, leading to microinfarcts. The microinfarcts show up as white matter hyperintensities (WMH) in MRI. Most research using WMH to study dementia has been completed with non-Hispanic whites (NHW), though studies have shown a higher incidence of metabolic factors related to AD in MA. It is our goal to use WMH to find further differences in vascular and metabolic factors related to AD among a cohort of NHW, MA, and AA. Method: A cross-sectional analysis of 2363 subjects from the HABS-HD cohort was conducted (967 NHW, 410 AA, and 986 MA). Participants underwent a clinical evaluation and a 3T brain MRI (Siemens Skyra). WMH volume was measured from FLAIR using the Statistical Parametric Mapping (SPM) Lesion Segmentation Tool. WMH were Log transform to achieve normality, and were adjusted for intracranial volume derived from Free3Surfer V6.0 analysis of T1MPRAGE. Fasting blood samples were collected, and clinical measures were conducted using standard procedures. Clinical, vascular, and metabolic risk factors (table 1) were used in linear regression models as predictors of WMH volume adjusted by intracranial volume (ICV). Age, sex, and education were entered as covariates. Results: The total sample was 62.3 percent female with a mean age of 65.4 years and 13.07 years of education. NHW were older, had more years of education, had lower BMI, lower systolic and diastolic blood pressure, and levels of triglycerides, HA1c, and EGFR when compared to AA and MA (p ≤0.005). In NHW, age, sex, education, SBP, DBP, and hypertension significantly predicted WMH volumes (p ≤ 0.005). Age, years of education and BMI were the only significant predictors of WMH volume in AA (p ≤ 0.005), while age, total cholesterol and T4 levels were significant predictors of WMH volume in MA (p ≤ 0.005). Having a diagnosis of diabetes or dyslipidemia, also predicted WMH volume in MA. Conclusion: Results showed that different factors contribute to WMH volume among different ethnicities. Results suggest that in NHW, a vascular profile is most relevant, while in MA and AA, a metabolic profile seems to be driven the association with WMH. Prospective studies are needed to further understand the how the different profiles among different ethnicities affect the presentation of WMH and pathology of SVD.