Linking vestibular function and sub-cortical grey matter volume changes in a longitudinal study of aging adults

Abstract

AbstractEmerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and alterations in the function and the structure of the central nervous system in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head-impulse tests to measure the horizontal semi-circular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of 1 (18.6%), 2 (49.5%) and 3 (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and inter-subject random variation in the baseline levels of and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the basal ganglia and thalamus at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (unadjusted p=0.038; 95% CI: 0.00397-0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (unadjusted p=0.046; 95% CI: 0.000727-0.0873) lower bilateral-mean volume of the thalamus for each 1-unit lower cVEMP amplitude. We also found a relationship between a lower mean VOR gain and lower left hippocampal volume (β=0.121, unadjusted p=0.018, 95% CI: 0.0212-0.222). There were no significant associations between volume and oVEMP. These findings provide insight into the specific brain structures that undergo atrophy in the context of age-related loss of peripheral vestibular function.Comprehensive SummaryHumans rely on their vestibular, or inner ear balance, system to manage everyday life. In addition to sensing head motion and head position with respect to gravity, the vestibular system helps to maintain balance and gaze stability. Furthermore, evidence is mounting that vestibular function is linked to structural changes in the central nervous system (CNS). Yet, the exact processes by which vestibular function alters brain structural integrity is unclear. One possible mechanism is that progressive vestibular deafferentation results in neurodegeneration of structures that receive vestibular input. In support of this putative mechanism, recent studies report the association of vestibular impairment with volume loss of brain areas that receive vestibular information, specifically the hippocampus and entorhinal cortex, in older adults. This present work investigates the extent over time to which age-related vestibular loss contributes to volume reduction of four brain regions that receive vestibular input: the hippocampus, entorhinal cortex, thalamus, and basal ganglia. Using data from a cohort of healthy, older adults between 2013 and 2017 from the Baltimore Longitudinal Study of Aging, we assessed regional brain volume as a function of vestibular function, while accounting for common confounds of brain volume change (e.g., age, sex, head size). We found that poor vestibular function is associated with significantly reduced volumes of the thalamus, basal ganglia, and left hippocampus. Notably, this study is one of the first to demonstrate relationships between age-related vestibular loss and gray matter loss in brain regions that receive vestibular input. Further research is needed to understand in greater detail the observed link between vestibular function and CNS structure. Which brain areas are impacted by age-related vestibular loss? How and in what sequence are they impacted? As the world’s aging population—and the prevalence of age-related vestibular impairment—increases, answering questions like these becomes increasingly important. One day, these answers will provide targets for preemptive interventions, like physical pre-habilitation, to stave off adverse changes in brain structure before they occur and progress towards clinical significance.