Clinical trial of vestibular therapy to reduce falls in patients with Alzheimer's disease

Project summary
Patients with Alzheimer’s disease (AD) are known to have greater balance and gait impairment and double
the rate of falls relative to healthy older adults (60-70% vs ~30%). Currently, few effective interventions
exist to manage and mitigate falls in AD, and unfortunately, falls continue to be one of the primary drivers of
morbidity, institutionalization, and mortality among AD patients. Recent studies have shown that AD patients
have a two-fold higher prevalence of vestibular impairment (~50%) relative to age-matched controls (~25%
prevalence). Additionally, in pilot data from an ongoing observational study, we have shown that vestibular
loss is associated with an increased rate of falls in AD patients. Vestibular therapy (VT) is a well-established
treatment for vestibular loss, and consists of physical therapy-based exercises designed to foster
compensation for reduced vestibular function. VT is effective in improving balance and reducing fall risk in
cognitively-intact patients with vestibular impairment. However, whether VT could be effective in improving
balance and reducing falls in AD patients with vestibular loss has never been explored. In this study, we
propose a randomized controlled trial of VT in 100 patients with mild-moderate AD who have vestibular
impairment. We will randomize patients 1:1 to a standard course of VT (1 session per week for 8 weeks) or
to an active control matched for effort and duration. We will compare the efficacy of VT vs. active control
primarily on 1-year incident fall rate. We will also investigate potential intermediate outcomes between VT
and falls – specifically balance outcomes (a predicted target of VT) and spatial cognitive outcomes (a novel
target of VT) – to understand potential mechanisms by which VT may influence fall rates. We hypothesize
that VT will have preliminary efficacy in reducing 1-year incident fall rates relative to an active control
intervention in a convenience sample of 100 patients with mild-moderate AD. We will also explore whether
VT has preliminary efficacy in improving balance and cognition relative to the active control intervention.
To accomplish the proposed study, we will recruit 100 patients from the Memory and Alzheimer’s
Treatment Center, a well-established AD clinical research resource at Johns Hopkins. Falls are a
disastrous outcome in patients with AD. If this pilot trial followed by a Phase III multi-center trial provide
strong evidence for the benefit of VT in reducing falls, this low-risk intervention could be widely
disseminated and implemented by an existing workforce and infrastructure, and produce substantial,
sustained change in AD clinical practice.

Grant Number: 5R01AG065259-05
NIH Institute/Center: NIH
Principal Investigator: Yuri Agrawal