Arterial stiffness is associated with prefrontal cortex integrity in ageing

Arterial stiffness, measured using pulse-wave velocity (PWV), is linked to an increased risk of cognitive decline and dementia, yet the underlying structural brain mechanisms remain unclear. This study examined whether PWV is linked to cortical thickness of the prefrontal cortex (PFC), a region essential for cognitive functioning. 124 older adults aged > 50 years with new-onset cognitive concerns without history of stroke or dementia underwent carotid-femoral PWV, magnetic resonance imaging (MRI) scans, and neuropsychological assessment. Cortical thickness of the medial, lateral and total prefrontal cortex was estimated using FastSurfer v2.4.0. Higher PWV was significantly correlated with reduced thickness of the total PFC (r = -.290, pFDR = .014), particularly of the left hemisphere (r = -.338, pFDR = .008). Significant associations were also found for the left medial PFC (r = -.238, pFDR = .014) and all lateral regions (left: r = -.338, pFDR = .002; right: r = -.287, pFDR = .009; total: r = -.394, pFDR < .001). Associations with the total, lateral, and left medial PFC remained significant after adjusting for age, sex, and traditional cardiovascular factors. Both increased PWV and decreased lateral PFC thickness were associated with poorer executive function, though no mediating role of the PFC was observed. This study is the first to demonstrate that PWV is associated with reduced cortical thickness of the PFC in older adults, independent of traditional cardiovascular risk factors. The findings highlight arterial stiffening as a potential modifiable risk factor of neurodegenerative and structural brain changes in ageing populations.