Cerebral Vasoreactivity Changes Over Time in Patients With Different Clinical Manifestations of Cerebral Small Vessel Disease

Objectives: Endothelial dysfunction (ED) has been linked to the pathogenesis of cerebral small vessel disease (SVD). We aimed to assess ED and cerebrovascular reactivity (CVR) in the patients with a diverse manifestation of SVD, with similar and extensive white matter lesions (WMLs, modified Fazekas scale grade ≥2), compared with a control group (CG) without the MRI markers of SVD, matched for age, gender, hypertension, diabetes, and to evaluate the change of CVR following 24 months. Methods: We repeatedly measured the vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery (MCA) by the transcranial Doppler ultrasound (TCD) techniques in 60 subjects above 60 years with a history of lacunar stroke (LS), vascular dementia (VaD), or parkinsonism (VaP) (20 in each group), and in 20 individuals from a CG. Results: The mean age, frequency of the main vascular risk factors, and sex distribution were similar in the patients with the SVD groups and a CG. The VMRr and the BHI were more severely impaired at baseline (respectively, 56.7 ± 18% and 0.82 ± 0.39) and at follow-up (respectively, 52.3 ± 16.7% and 0.71 ± 0.38) in the patients with SVD regardless of the clinical manifestations (ANOVA, p > 0.1) than in the CG (respectively, baseline VMRr 77.2 ± 15.6%, BHI 1.15 ± 0.47, p < 0.001; follow-up VMRr 74.3 ± 17.6%, BHI 1.11 ± 0.4, p < 0.001). All the assessed CVR measures (VMRr and BHI) significantly decreased over time in the subjects with SVD (Wilcoxon's signed-rank test p = 0.01), but this was not observed in the CG (p > 0.1) and the decrease of CVR measures was not related to the SVD radiological progression (p > 0.1). Conclusions: This study provided evidence that the change in CVR measures is detectable over a 24-month period in patients with different clinical manifestations of SVD. Compared with the patients in CG with similar atherothrombotic risk factors, all the CVR measures (BMRr and BHI) significantly declined over time in the subjects with SVD. The reduction in CVR was not related to the SVD radiological progression.