Reliability, reproducibility and validity of dynamic cerebral autoregulation in a large cohort with transient ischaemic attack or minor stroke

Objective: Cerebral autoregulation (CA) is critical to maintenance of cerebral perfusion but its relevance to the risk of stroke and dementia has been under-studied due to small study sizes and a lack of consensus as to the optimal method of measurement. We determined the reliability and reproducibility of multiple CA indices and the effect of intensive data-processing in a large population with transient ischaemic attack or minor stroke. Approach: Consecutive, consenting patients in the population-based Oxford Vascular Study (OXVASC) Phenotyped cohort underwent up to 10-min supine continuous blood pressure monitoring (Finometer) with bilateral middle cerebral artery (MCA) transcranial ultrasound (DWL-Dopplerbox). Un-processed waveforms (Un-A) were median-filtered, systematically reviewed, artefacts corrected and their quality blindly graded (optimal (A) to worst (E)). CA metrics were derived in time-domain (autoregulatory index (ARI), Pearson's Mx, Sx, Dx) and in very-low (VLF) and low-frequency (LF) domains (WPS-SI: wavelet phase synchronisation, transfer function analysis), stratified by recording quality. Reliability and reproducibility (Cronbach's alpha) were determined comparing MCA sides and the first vs. second 5-min of monitoring. Main results: In 453 patients, following manual data-cleaning, there was good reliability of indices when comparing MCA sides (Mx: 0.77; WPS-SI-VLF: 0.85; WPS-SI-LF 0.84), or repeated five minute epochs (Mx: 0.57; WPS-SI-VLF: 0.69; WPS-SI-LF 0.90), with persistently good reliability between sides even in lower quality Groups (Group D: Mx: 0.79; WPS-SI-VLF: 0.92; WPS-SI-LF: 0.91). Reliability was greatest for Pearson's Mx and wavelet synchronisation index, with reasonable reliability of transfer function analyses, but ARI was prone to occasional, potentially defective, extreme estimates (left vs right MCA: 0.68). Significance: Resting-state measures of CA were valid, reproducible and robust to moderate noise, but require careful data-processing. Mx and wavelet synchronisation index were the most reliable indices for determining the prognostic value of CA in large epidemiological cohorts and its potential as a treatment target.