Effect of hearing ability on inflammation and glymphatic function affecting cognition in older adults

The mechanisms linking hearing ability, inflammation, glymphatic system function, and cognitive impairment in older adults are largely unknown. To investigate this issues, magnetic resonance imaging (MRI) was used to test for dysfunctions in the glymphatic system of older adults with hearing loss and to determine the relationship of glymphatic dysfunction, inflammation and cognitive deficits. This cross-sectional observational study included participants with ARHL and healthy controls (HCs) between January 2021 and December 2023. Participants underwent MRI scans of the glymphatic indices and clinical assessment of auditory, neuropsychological, and inflammatory measures. Multimodal MRI indices were used as proxies of glymphatic function and compared with measures of inflammation and cognition dysfunction in the older adults with hearing loss and control groups. Mann-Whitney U test, Spearman rank correlation and Mediation analysis were conducted. A total of 130 hearing loss patients (mean age years, 64.10 ± 3.43 [SD], 67 males) and 121 healthy controls (mean age years, 63.55 ± 3.49 [SD], 68 males) were included. The hearing loss group differed significantly from normal hearing control on MRI glymphatic measures of choroid plexus volume (CPV) (1.48 vs 1.37, p = 0.0004), enlarged perivascular spaces (EPVS) (1.74 vs 1.55, p < 0.0001) and diffusion tensor image analysis along the perivascular space (DTI-ALPS) (1.47 vs 1.63, p < 0.0001). Hearing loss severity was associated with higher values of CPV and EPVS and lower values of ALPS and strongly correlated with higher levels of inflammation (all FDR q < 0.05). Mediation analysis showed that ALPS and CPV mediate the relationship between hearing loss and scores on the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST), respectively. Our findings support a potential associative pathway that inflammation and glymphatic dysfunction act as plausible intermediate factors facilitating the pathological relationship linking the increase in hearing loss in older adults to decline in cognition.