Impact of vestibular loss on central vestibular pathways in aging adults

Emerging research is providing compelling evidence that the vestibular system contributes not only to basic
reflexes (e.g. vestibulo-ocular, postural) but also to complex cognitive processes including spatial memory
and navigation; self-motion perception and motor planning; and executive function. Vestibular function
declines with healthy aging, and studies from our group and others have shown that vestibular loss in aging
adults is associated with known age-related reductions in cognitive skills including spatial memory and
navigation ability, and self-motion perception and motor planning. In a pilot study supported by the NIDCD,
we found that older adults with vestibular loss had reduced hippocampal volumes, as well as atrophy of
subfields of the thalamus and the basal ganglia. During this pilot study, our group built a pipeline for analysis
of neuroimaging data from the Baltimore Longitudinal Study of Aging (BLSA) at the Center for Imaging
Science (CIS) in the Johns Hopkins Department of Biomedical Engineering. We established the
computational infrastructure for both volumetric analysis and shape analysis. In this proposal, we seek to
leverage this infrastructure to more comprehensively investigate the impact of aging on three core central
vestibular pathways, and examine the link between structural changes in these pathways and functional
changes in clinical skills mediated by these pathways. Specifically, we aim to: Aim 1 Investigate the
relationship between peripheral vestibular sensory loss associated with aging and the structure of central
vestibular pathways, specifically considering 3 primary central vestibular pathways: 1) spatial cognitive; 2)
sensorimotor; 3) prefrontal cortex (executive function). Aim 2 Examine the longitudinal relationships
between peripheral vestibular loss and structural changes in central vestibular pathways using longitudinal
models and also the novel change-point model in aging adults. Aim 3 Explore the association between
structural changes in central vestibular pathways and clinical functional changes cross-sectionally and
longitudinally. This proposal represents a unique opportunity to leverage strengths in vestibular physiology
and computational neuroimaging to increase our fundamental understanding of the impact of healthy aging
on central vestibular networks, and associated clinical consequences. Findings from this study will be used
to drive further critical research questions, including 1) Does vestibular loss contribute to the accelerated
decline in cognitive ability and brain structure that occurs in individuals with cognitive impairment and
Alzheimer’s disease; and 2) Can vestibular interventions for vestibular loss prevent/mitigate changes in
central vestibular pathways?

Grant Number: 5R01AG073115-06
NIH Institute/Center: NIH
Principal Investigator: Yuri Agrawal