Brain arterial dilatation modifies the association between extracranial pulsatile hemodynamics and brain perivascular spaces: the Northern Manhattan Study

Abstract

Pulsatile hemodynamics are associated with brain small perivascular spaces (SPVS). It is unknown whether the stiffness of intermediary arteries connecting the aorta and brain modifies this association. Participants from the Northern Manhattan Study were assessed for SPVS (defined as ≤3 mm T1 voids) and white matter hyperintensity volume (WMH) using MRI. Middle (MCA) and anterior cerebral arterial (ACA) diameters (measured on time-of-flight MRA) and CCA strain (assessed by ultrasound) were used as surrogates of stiffness. Brachial and aortic pulse pressure (PP) and aortic augmentation index (Aix, assessed by applanation tonometry) were used as markers of pulsatility. We tested whether stiffness in intermediary arteries modifies the association between extracranial pulsatility with SPVS and WMH. We found that among 941 participants (mean age 71 ± 9 years, 60% women, 66% Hispanic), the right MCA/ACA diameter was associated with right anterior SPVS (B = 0.177, P = 0.002). Brachial PP was associated with right anterior SPVS (B = 0.003, P = 0.02), and the effect size was bigger with right MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). The association between right CCA strain and ipsilateral SPVS was modified by MCA/ACA diameter, with the largest effect size in those with ipsilateral MCA/ACA diameter in the upper tertile (P = 0.001 for the interaction). Similar dose-effects and statistical interactions were replicated using aortic AIx or aortic PP. We found no evidence of effect modification between pulsatile measures and WMH by stiffness measures. In summary, pulsatile hemodynamics relate to brain SPVS, and the association is the strongest among individuals with dilated brain arteries.

Keywords: Brain arterial dilatation; Dolichoectasia; Perivascular spaces; Pulse pressure.; Stiffness.

Figure 1:. Correlation between dilatation of brain arteries and ipsilateral downstream perivascular spaces.

In panel A, the right anterior and middle cerebral arteries seem dilated, possibly in relationship to compensatory changes given the absence of a contralateral first segment of the anterior cerebral artery. The brain MRI shows evidence of dilated perivascular spaces in the basal ganglia, more demarcated in the right caudate and anterior putamen regions, both which are perfused through penetrating arteries arising from the ipsilateral first segments of the anterior and middle cerebral arteries. On the contralateral basal ganglia, there are dilated perivascular spaces which appear smaller and less well demarcated.