Cerebrovascular reactivity is related to enlarged perivascular spaces in the basal ganglia among cognitively normal older adults

Abstract Background Cerebral small vessel disease (cSVD) is characterized by several in‐vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are fluid‐filled spaces that play a role in the glymphatic system’s removal of brain waste. Arterial pulsatility drives waste removal through the PVS. Thus, arterial stiffness, a common feature of brain aging, may lead to waste accumulation and perivascular space enlargement. Method We explored the relationship between arterial stiffness and ePVS counts in 80 cognitively normal older adults ranging in age from 60‐85. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. Arterial stiffness was assessed using cerebrovascular reactivity (CVR), a measure of the ability of cerebrovasculature to dilate in response to hypoxia. Blood‐oxygen‐level‐dependent contrast imaging (BOLD) functional magnetic resonance imaging (fMRI) was used in conjunction with blocked administration of hypercapnic gas. CVR was computed in specific regions by dividing change in BOLD signal by change in end‐tidal CO 2 . All ePVS counts were performed on T1 MPRAGE and T2 FLAIR images while blinded to participant demographics and under the direction of a neuroradiologist. ePVS were defined as regions of hypointensity less than 3mm in diameter on T1 imaging and were distinguished from mimics by absence of T2 FLAIR hyperintensity. ePVS were individually and manually counted in a single, representative slice in the axial plane of the basal ganglia (BGePVS), centrum semiovale, hippocampus, and midbrain. Result Regression analyses controlling for age, sex, intracranial volume, and education demonstrated a significant, negative relationship between cross‐sectional whole brain CVR and BGePVS (β =‐0.338, P = 0.003). Moreover, CVR in the left basal ganglia was negatively related to BGePVS in the left basal ganglia (β = ‐0.401, P < 0.001), and CVR in the right basal ganglia was negatively related to BGePVS in the right basal ganglia (β = ‐0.444, P < 0.001). Conclusion Our findings indicate a regional relationship between lower CVR and BGePVS burden, suggesting BGePVS are related to arterial stiffness. Longitudinal studies are required to address causality. Future work should compare other potential mechanisms of perivascular space enlargement to strengthen the hypothesis that arterial stiffness leads to ePVS.