Cerebrovascular reactivity in obstructive sleep apnea: A systematic review using BOLD MRI.

BACKGROUND

Obstructive sleep apnea (OSA) is a major risk factor for stroke and cognitive decline, although its effects on cerebrovascular reactivity (CVR) remain unclear. However, it remains unknown whether blood-oxygen-level-dependent (BOLD) MRI captures consistent CVR impairment or compensatory changes in OSA.

AIM: Here, we systematically synthesize BOLD MRI studies of CVR in adults with OSA to resolve these discrepancies.

METHODS

We searched five databases through October 2025 for human studies reporting hypercapnia- or breath-hold-evoked BOLD CVR in polysomnography-confirmed OSA, with duplicate screening, JBI risk-of-bias assessment, and random-effects pooling of PETCO2-referenced %BOLD·mmHg-1 where possible.

RESULTS

Six studies met criteria; four case-control comparisons (n = 84 OSA; n = 55 controls) and two CPAP trials. Contrary to the prevailing view that OSA uniformly blunts CVR, pooled PETCO2-referenced data revealed higher global CVR in OSA than controls (mean difference +0.05 %BOLD·mmHg-1, 95 % CI 0.03-0.06; P < 0.001), with similarly increased grey and white matter reactivity. Studies using alternative CVR metrics uncovered regionally reduced vasodilatory volume or perfusion-based flow reactivity in OSA, aligning previously unresolved dissociations between BOLD and perfusion-derived CVR. Within OSA, one therapeutic CPAP trial demonstrated regional increases in CVR, whereas short-term CPAP withdrawal did not alter BOLD CVR.

CONCLUSIONS

These findings reveal that BOLD CVR in OSA is heterogeneous rather than uniformly reduced and establish PETCO2-referenced BOLD MRI as a marker of cerebrovascular dysregulation, providing a new framework for CVR standardisation and opening the door to biomarker-based cerebrovascular risk stratification and CPAP response monitoring.