Neurovascular Resilience and Autonomic Inertia: The Impact of Age and Sex on Intracranial Dynamics During Stress

Systemic vascular dynamics and autonomic nervous system (ANS) regulation are pivotal for maintaining cerebral homeostatic stability; however, the aging process and biological sex significantly modulate these neural feedback loops. This study investigated the neurobiological interaction between cardiac autonomic modulation and intracranial pulse waveform morphology (P2/P1 ratio) during isometric stress across distinct age and sex cohorts. We evaluated 320 individuals (184 women; 136 men), stratified into young (n = 151) and older adults (n = 169) groups. Heart rate variability (HRV) and intracranial pulse waveform morphology (P2/P1 ratio), monitored via non-invasive strain-gauge technology, were assessed at baseline, during a 1-min isometric handgrip challenge, and during a 5-min post-stress recovery, with data analyzed using a three-way ANOVA. Older adults exhibited significantly altered intracranial pulse waveform morphology (elevated P2/P1 ratio) and attenuated HRV compared to younger subjects, independent of sex. Importantly, we identified a phenomenon of "sympathovagal lag" in older adults, characterized by persistent sympathetic dominance (0V pattern) following stress cessation, contrasting with the rapid homeostatic recovery observed in younger individuals. Regarding sex, older women demonstrated the most compromised intracranial compensatory status despite maintaining higher parasympathetic tone. Aging is linked to significant autonomic inertia and diminished intracranial reserve; the prolonged post-stress sympathetic response in older age suggests a window of vulnerable cerebrovascular regulation, and our results establish the P2/P1 ratio as a reliable, non-invasive biomarker of age-associated neurophysiological dysregulation.