BLOOD PRESSURE AND BLOOD GLUCOSE ARE ASSOCIATED WITH MYELIN VULNERABILITY IN AN ETHNICALLY DIVERSE SAMPLE OF OLDER ADULTS

Abstract

Hypertension and Type 2 diabetes are cardiovascular disease risk factors (CVD-RFs) associated with pathological aging, including Alzheimer's disease (AD) and vascular dementia. Mid-life hypertension and diabetes predict late-life white matter alterations including white matter hyperintensities (WMH) associated with dementia. Further, evidence suggests that these CVD-RFs may exert their impact as early as the third or fourth decade of life in affected individuals. Hypertension and diabetes are two of the most prevalent CVD-RFs in minority populations, and rates of treatment-related control in these populations lag behind those of non-Hispanic Whites. Work is needed to detect white matter vulnerability associated with CVD-RFs before overt damage occurs. Given that myelin degradation is thought to contribute to white matter damage, we focused this study on multicomponent driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) as it relates to CVD-RFs in an ethnically diverse sample of older adults. Forty-six non-demented/non-depressed participants (mean age=66.4 years; 56% female; equal % Black/Hispanic/non-Hispanic White) underwent 3T MRI. mcDESPOT quantified ‘restricted’ water trapped within the lipid bilayers of myelin sheath, providing a measure of myelin water fraction (MWF). Regardless of medication status, systolic blood pressure (SBP) was determined via two readings separated by 5-minute intervals; blood glucose was measured by fasting levels of hemoglobin A1c. Separate age-adjusted linear regressions investigated the associations between SBP and A1c on whole-brain MWF. Analyses were fully corrected for multiple comparisons and utilized threshold-free cluster enhancement. Higher SBP was associated with lower MWF within deep white matter and parietal regions (p<.05), whereas greater A1c was associated with lower MWF in deep white matter and more temporal regions (p<.05; see Figure 1a). Similar associations were noted in a subset of fifteen Hispanics at increased risk for uncontrolled CVD-RFs (see Figure 1b). Higher levels of SBP and A1c are associated with decreased myelin integrity in a sample of older, ethnically diverse adults. These results suggest that mcDESPOT may be a useful tool to detect the adverse effects of CVD-RFs on white matter integrity in and around areas of WMH in older non-demented/non-depressed adults. Age-adjusted associates of myelin water fraction with systolic blood pressure (red) and fasting blood glucose (blue) fully corrected for multiple comparisons: Threshold-Free Cluster Enhancement p<.05 in 46 adults (a) and 15 Hispanics (b).