Neurovascular decoupling: An early indicator of cognitive decline

Abstract

Background Cognitive decline in Alzheimer's disease (AD) is increasingly linked to cerebrovascular dysfunction, including small vessel disease (SVD). Conventional SVD MRI markers primarily detect late-stage structural damage. Neurovascular coupling (NVC) has emerged as an early indicator of cerebrovascular function and is cross-sectionally associated with cognition, but its association with longitudinal decline remains unclear. Objective To investigate whether baseline NVC is associated with cognitive decline over 3.5 years in individuals ranging from no cognitive complaints to memory clinic patients with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI). Methods Seventy-five participants underwent cognitive assessment and MRI, including BOLD fMRI during visual stimulation to assess NVC. Cognitive decline was analyzed as dichotomous outcome (stable versus decline; n = 75) using logistic regression and as continuous outcome for domain-specific change (z-score change; n = 69) using linear regression. Results Lower baseline NVC was associated with global cognitive decline, both dichotomously (OR = 42.29, p = 0.017) and continuously (B = 0.45, p = 0.012). Baseline NVC was also associated with a decline in executive function (B = 0.47, p = 0.043), but not with other domain-specific decline. Among conventional SVD MRI markers, only lacunar infarcts were associated with decline (OR = 4.12, p = 0.037). Conclusions Baseline NVC appears to be a predictor of global cognitive decline, outperforming most conventional SVD MRI markers. These findings support the potential utility of NVC as a prognostic marker of cognitive decline in early-stage AD, highlighting its promise for early intervention strategies targeting cerebrovascular dysfunction.