Association of Carotid Plaque and Flow Velocity With White Matter Integrity in a Middle-aged to Elderly Population

Abstract

Background and Objectives:It is uncertain whether there is an association of carotid plaques (CP) and flow velocities with peak-width mean diffusivity (PSMD) and white matter hyperintensities (WMH) independent of shared risk factors. We aimed to study this association controlling for biomarkers of inflammation and cardiac dysfunction as well as typical cardiovascular risk factors and spatial distribution.Methods:We included participant from the population-based Hamburg City Health Study, recruiting citizens between 45 and 74 years of age. Medical history was obtained from structured interviews and extended laboratory tests, physical examinations, MRI of the head, echocardiography, abdominal and carotid ultrasound were performed. We performed multivariable regression analysis with PSMD, periventricular, deep, and total volume of WMH (pWMH, dWMH, tWMH) as dependent variables. PSMD was calculated as the difference between the 95th and 5th percentile of MD values on the white skeleton in standard space Volumes of WMH were determined by application of a manually trained k-nearest neighbor segmentation algorithm. WMH measured within a distance of 1 cm from the surface of the lateral ventricles were defined as pWMH, and above 1 cm as dWMH.Results:2623 participants were included. Median age was 65 years and 56% were women. Their median tWMH was 946 mm3(IQR:419, 2164), PSMD 2.24 mm2 /s x 10-4 (IQR: 2.04,2.47), peak systolic velocity (PSV) of internal carotid arteries 0.70m/sec (IQR:0.60, 0.81), and 35% had CP. Adjusted for age, sex, high-sensitive CRP, NT-proBNP, and commonly measured cardiovascular risk and systemic hemodynamic factors, both CP (B=0.15;CI:0.04, 0.26;p=0.006) and low PSV (B=-0.49; CI:-0.87,-0.11;p=0.012) were significantly associated with a higher tWMH and PSMD. Low PSV(B=-0.48;CI:-0.87,-0.1;p=0.013) was associated with pWMH, and presence of CP with pWMH (B=0.15; CI:0.04,0.26; p=0.008) and dWMH (B=0.42; CI:0.11,0.74; p<0.009).Conclusion:Low PSV and CP are associated with WMH and PSMD independent of cardiovascular risk factors and biomarkers of inflammation and cardiac dysfunction. This points towards pathophysiological pathways underlying both large and small vessel disease beyond the common cardiovascular risk profile.Trial Registration Information:The trial was submitted at www.clinicaltrials.gov, under NCT03934957 on January 4 2019. The first participant was enrolled in February 2016.

A latent clinical-anatomical dimension relating metabolic syndrome to brain structure and cognition

“…MetS affects brain health in a complex manner with interacting effects on the cerebral vasculature and parenchyma as shown by histopathological and imaging studies. 24 Pathophysiological aspects of MetS comprise (1) atherosclerosis impairing parenchymal blood supply by promoting acute and chronic hypoperfusion as well as triggering inflammatory processes; [39][40][41] (2) endothelial dysfunction leading to diminished cerebral vasoreactivity rendering the vasculature less responsive to stimuli tailoring the blood flow to the brains metabolic needs; 42,43 (3) blood-brain barrier breakdown causing plasma proteins and immunoglobulins to enter neural tissue while the efflux of waste products is hindered collectively inducing an inflammatory response; 44 (4) oxidative stress impairing neuronal integrity and leading to mitochondrial dysfunction. 45 Together, these effects culminate in (5) small vessel injury causing a variety of pathologies -inter alia, white matter damage, microinfarcts and cerebral microbleeds.…”