Synergistic effects of cerebrovascular reactivity and gray matter volume on executive function in aging

Background Age-related impairments in cerebrovascular reactivity (CVR) and gray matter volume (GMV) both contribute to cognitive decline, yet their regional interplay and joint impact on cognition remain unclear. Objective To investigate how CVR and GMV are coupled and interact regionally to influence cognition in normal aging. Methods We examined 181 healthy younger adults (18–34 years) and 120 older adults (60–89 years). CVR and GMV (% intracranial volume) in major brain lobes were quantified using resting-state multi-echo functional MRI and structural MRI, respectively. Age-related alterations were defined by standardizing older adults’ values relative to the younger group. Spearman correlations, linear regression models, and interaction analyses were performed. Results CVR and GMV were not significantly correlated across frontal, temporal, parietal, or occipital lobes (ρ: −0.15 to −0.06; all p > 0.05). However, significant CVR × GMV interaction effects on executive function were found in parietal and occipital lobes ( p -interaction=0.015 and 0.026). In the occipital lobe, compared with the “low CVR decline + low GMV loss” group, “high CVR decline + low GMV loss” (β=−0.47, p = 0.004) and “high CVR decline + high GMV loss” (β=−0.60, p < 0.001), but not “low CVR decline + high GMV loss” (β=−0.23, p = 0.127), were significantly associated with poorer executive function. Conclusions CVR and GMV interacted to support executive function in parietal and occipital lobes. Occipital CVR decline linked to poorer executive performance irrespective of GMV status. These findings highlight the importance of multi-modal, cross-scale assessments and suggest CVR as a sensitive marker of executive decline beyond structural measures alone.