Paired neuronal-haemodynamic neurovascular coupling measures and cognitive performance in vascular pathology: protocol for a systematic review and meta-analysis

Abstract

Neurovascular coupling (NVC) links neuronal activity to haemodynamic responses. Altered NVC may contribute to cognitive impairment in vascular pathology, but evidence is limited by inconsistent definitions and by the conflation of paired neuronal–haemodynamic NVC measures with haemodynamic-only, model-derived, or imaging-derived proxy measures. The primary aim is to evaluate the association between paired neuronal–haemodynamic NVC measures and cognitive performance in middle-aged and older adults with vascular pathology. Secondarily, we will compare paired neuronal–haemodynamic NVC measures between patients with vascular pathology and age-matched controls without vascular pathology, determine whether predefined pathology strata show distinct impairment profiles, and examine whether the NVC–cognition association varies across cognitive domains. As an exploratory objective, we will synthesise evidence on the prognostic utility of paired neuronal–haemodynamic NVC measures in predicting future cognitive decline. Collectively, these objectives address critical gaps in a fragmented literature characterised by heterogeneous methodologies, populations, and assessment techniques, as well as methodological limitations including small samples, cross-sectional designs, and inadequate confounder control. This review will systematically synthesise existing findings, identify remaining knowledge gaps, and outline priorities for future research. This protocol follows PRISMA-P guidance and is registered with PROSPERO (CRD420261351976). We searched five electronic databases from inception to 28 July 2026 for peer-reviewed English-language studies. Eligible studies include middle-aged and older adults with vascular pathology and/or participants from relevant comparator groups and report paired neuronal–haemodynamic NVC measures based on independently acquired neuronal and haemodynamic or vascular signals. The primary synthesis will evaluate associations between paired neuronal–haemodynamic NVC measures and cognitive performance, with meta-analysis conducted only for synthesis strata that meet prespecified feasibility criteria.