Neurovascular-metabolic coupling links hearing loss to cognitive impairment: Evidence from GABA and cerebral blood flow in presbycusis

Hearing loss is recognized as the leading modifiable risk factor for dementia. However, the neurobiological pathways bridging auditory dysfunction and cognitive decline remain poorly understood. We hypothesized that a neurovascular-metabolic cascade, involving neurotransmitter imbalances and perfusion deficits, underlies this link. We recruited 124 patients with presbycusis and 91 age-matched health controls. Auditory GABA and glutamate levels were quantified using macromolecule-suppressed MEGA-PRESS, and cerebral blood flow (CBF) was quantified using pseudo-continuous arterial spin labeling. Participants underwent comprehensive neuropsychological assessments. Spatial correlation analysis was performed to align CBF alterations with established neurotransmitter maps. Presbycusis patients exhibited bilateral reductions in auditory GABA and glutamate, alongside widespread hypoperfusion across auditory, salience, and executive control networks. Mediation analysis demonstrated that right auditory GABA concentrations and regional CBF (specifically in the right superior parietal gyrus and left thalamus) sequentially mediated the association between hearing loss and cognitive deterioration. Furthermore, CBF alterations spatially co-localized with serotonergic, dopaminergic, and GABAergic systems, with these spatial couplings significantly correlating with cognitive performance. These findings delineate a systemic neurovascular-metabolic cascade linking hearing loss to cognitive impairment. By identifying GABAergic signaling and regional perfusion as key mediators, this study provides a multimodal framework for understanding sensory-cognitive aging and highlights potential biomarkers for early intervention in dementia.