Midlife and Late-Life Vascular Risk Factors and White Matter Microstructural Integrity: The Atherosclerosis Risk in Communities Neurocognitive Study

Abstract

Background: Diffusion tensor imaging measures of white matter (WM) microstructural integrity appear to provide earlier indication of WM injury than WM hyperintensities; however, risk factors for poor WM microstructural integrity have not been established. Our study quantifies the association between vascular risk factors in midlife and late life with measures of late-life WM microstructural integrity.

Methods and results: We used data from 1851 participants in ARIC (Atherosclerosis Risk in Communities Study) who completed 3-T magnetic resonance imaging, including diffusion tensor imaging, as part of the ARIC Neurocognitive Study (ARIC-NCS). We quantified the association among lipids, glucose, and blood pressure from the baseline ARIC visit (1987-1989, ages 44-65, midlife) and visit 5 of ARIC (2011-2013, ages 67-90, late life, concurrent with ARIC-NCS) with regional and overall WM mean diffusivity and fractional anisotropy obtained at ARIC visit 5 for ARIC participants. We also considered whether these associations were independent of or modified by WM hyperintensity volumes. We found that elevated blood pressure in midlife and late life and elevated glucose in midlife, but not late life, were associated with worse late-life WM microstructural integrity. These associations were independent of the degree of WM hyperintensity, and the association between glucose and WM microstructural integrity appeared stronger for those with the least WM hyperintensity. There was little support for an adverse association between lipids and WM microstructural integrity.

Conclusions: Hypertension in both midlife and late life and elevated glucose in midlife are related to worse WM microstructural integrity in late life.

Keywords: blood pressure; epidemiology; leukoencephalopathy; risk factor; type 2 diabetes mellitus.

Figure 1

Comparison of primary and WMH‐adjusted analyses of the association of mid‐ or late‐life cardiovascular risk factors with overall WM FA. CI indicates confidence interval; DBP, diastolic blood pressure; FA, fractional anisotropy; HDL‐c, high‐density lipoprotein cholesterol; LDL‐c, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; WM, white matter; WMH, white matter hyperintensity.

Figure 2

Comparison of primary and WMH‐adjusted analyses of the association of mid‐ or late‐life cardiovascular risk factors with overall WM MD. CI indicates confidence interval; DBP, diastolic blood pressure; HDL‐c, high‐density lipoprotein cholesterol; LDL‐c, low‐density lipoprotein cholesterol; MD, mean diffusivity; SBP, systolic blood pressure; WM, white matter; WMH, white matter hyperintensity.

Figure 3

The adjusted association between cardiovascular risk factors at visit 1 or 5 and measures of overall white matter fractional anisotropy by decile of intracranial‐volume standardized WMH volumes. CI indicates confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure; WMH, white matter hyperintensity.

Figure 4

The adjusted association between cardiovascular risk factors at visit 1 or 5 and measures of overall white matter mean diffusivity by decile of intracranial‐volume standardized WMH volumes. CI indicates confidence interval; DBP, diastolic blood pressure; SBP, systolic blood pressure; WMH, white matter hyperintensity.