ABSTRACT NUMBER: ESOC2026A1484 POTENTIAL ROLE OF IMPAIRED CEREBRAL AUTOREGULATION AS A MARKER OF PHYSIOLOGICAL DYSFUNCTION IN CEREBRAL SMALL VESSEL DISEASE: AN OXHARP TRIAL ANALYSIS

Abstract Background and aims Cerebral small vessel disease (cSVD) is associated with cerebral endothelial and haemodynamic dysfunction but the role of impaired cerebral autoregulation (CA) is unknown. Methods OxHARP is a randomised, double-blind, crossover trial, comparing the cerebrovascular haemodynamic effects of sildenafil versus placebo in mild-moderate cSVD. During at-least 5 minutes of bilateral TCD and BP monitoring, we derived autoregulatory indices in the frequency domain (Transfer-function gain, phase and coherence at <0.05Hz(VLF),0.05-0.15Hz(LF),0.15-0.4Hz(HF)) and time domain (Autoregulatory Index-ARI and Mx). Standardised linear regression adjusting for age, sex and cerebral blood flow velocity examined associations between CA, WMH burden (as volume on MRI or ordinal severity on any imaging) and age. Results Among 60/75 participants (mean 68 years, 58% male), ARI reduced with increasing WMH-severity (Figure-1), comparing mild versus moderate or severe disease, whilst Mx reduced with increasing WMH-volume. Unadjusted frequency domain indices were non-significantly reduced. Associations between WMH volume and ARI or Mx were no longer significant when adjusting for age, despite similar magnitudes, and only reduced VLF gain remained independently associated with WMH (β=-0.40/SD, 95%CI 0.78 to -0.02, p = 0.040). Conclusions Cerebral autoregulation was impaired with increasing white matter hyperintensities in time-domain analyses, suggesting potential mechanistic links between CA and cSVD. However, it was unclear if this relationship was independent of age and further research will be required to discriminate the potential of autoregulation as a marker of endothelial dysfunction. Conflict of interest Kevin Wong. nothing to disclose. Figure 1 - belongs to Results