The Relationship between Vascular Risk Factors and White Matter Structural and Vascular Imaging Metrics

Abstract

AbstractBackgroundVascular risk factors are associated with cerebral small vessel disease and dementia pathology and reduced WM integrity is correlated with the severity of cognitive impairment in dementia. We have investigated if vascular risk factors are related to white matter structural and vascular imaging metrics. Imaging metrics include intracellular volume fraction (ICVF), white matter hyperintensities (WMH), and cerebrovascular measures such as cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and arterial transit time (ATT).MethodSixty‐four subjects (Table 1) enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort underwent MRI, including T2 FLAIR, neurite orientation dispersion and density imaging (NODDI), pseudo‐continuous ASL (PCASL). CVR was measured as a percent of increased CBF during a hypercapnic respiratory paradigm. ATT and resting CBF were obtained from a multi‐TI PCASL sequence. ICVF was obtained from NODDI. Head size adjusted WM total lesion volume (TLV) was calculated using SPM12‐LST2 toolbox with T2‐FLAIR image. Linear regression models were performed to examine if CBF, CVR, ATT, ICVF, or TLV are related to the risk factors or cognitive status adjusted covariates: age, sex, and years of education. A covariates adjusted logistic regression estimated weighting factors for each interrelated vascular imaging parameter to create novel cerebrovascular functional composites for each vascular risk group and mild cognitive impairment (MCI) group. The factor score p‐values were also calculated from two‐sample t‐tests with the cerebrovascular composite. The entire analyses were performed within the whole brain WM.ResultIn the whole brain WM, hypertension subjects (p=0.031) showed higher CVR (Figure 1). T2DM subjects (p=0.007) showed higher WM TLV (Figure 2). T2DM and MCI subjects showed lower ICVF than normal subjects did (Figure 3). Based on the weights of each cerebrovascular parameter in the composite (Table 2), the effects of CBF and CVR are stronger in hypertension group while all three cerebrovascular measures had substantial contribution to cognition status.ConclusionEach risk factor and cognitive status differently affected WM structural and vascular dynamic imaging parameters. The findings warrant further investigations of contributions of vascular risk factors to the structural and vascular abnormalities in dementia.