The burden of Alzheimer’s disease (AD) and AD-related dementias (AD/ADRD) is enormous for affected individuals (an estimated 46.8 million people worldwide in 2015), caregivers, and healthcare costs (estimated to be $159-$215 billion in 2010, with a projected increase to $379-$511 billion in 2040 in the US). Across the Veterans Integrated Service Network (VISN), the estimated prevalence of AD/ADRD ranges from 5.8% to 9.4%. The incidence of dementia is expected to almost double worldwide every 20 years, to 74.7 million in 2030 and 131.5 million in 2050. Because currently available dementia medications have considerable side effects while offering only limited benefits, non-pharmacological interventions for dementia are highly desirable. Preventing Loss of Independence through Exercise (PLIÉ) is a non-pharmacological, multi-domain, integrative group exercise program developed by researchers at the University of California, San Francisco (UCSF) and the San Francisco Veterans Affairs Medical Center (SF VAMC) for individuals AD/ADRD. The development of PLIÉ was informed by basic neuroscience findings that individuals with AD/ADRD have a preserved ability to learn perceptual and motor skills through repeated exposure despite having an impaired ability to consciously recall new information. Thus, PLIÉ focuses on training perceptual and motor skills that build strength and enhance the capacity to perform the movements that are most needed for daily function (e.g., transitioning safely from sitting to standing) and help individuals with AD/ADRD maintain functional independence. Additionally, PLIÉ incorporates the “best elements” from different Eastern and Western exercise modalities, particularly greater in-the-moment body awareness and social connection.

We have pilot tested the PLIÉ intervention at an adult day program in San Francisco. Six seniors with mild to moderate AD/ADRD were randomly assigned to participate in the PLIÉ program for 18 weeks, 2 to 3 days/week (depending on their daily attendance at the adult day program) while five seniors with mild to moderate AD/ADRD were randomly assigned to engage in the standard chair-based exercises at the adult day program (i.e., Usual Care). Compared to seniors in the Usual Care group, seniors who took part in PLIÉ showed improved cognitive function (as assessed by the cognitive subscale of the Alzheimer’s Disease Assessment Scale), improved physical performance (as assessed by the Short Physical Performance Battery), and improved quality of life (as assessed by the Quality of Life in Alzheimer’s Disease questionnaire) at the end of 18 weeks. Importantly, PLIÉ also had a beneficial effect on the caregivers, who reported reduced caregiver burden and distress related to their loved one’s AD/ADRD behaviors.

Based on the strength of this promising pilot data, the Department of Veterans Affairs’ (VA’s) Office of Rehabilitation Research and Development awarded study co-investigator Dr. Deborah Barnes funding to conduct a randomized clinical trial of PLIÉ. However, the budget of the VA grant did not allow for a neuroimaging component to investigate PLIÉ’s underlying neural mechanisms. Therefore, the proposed study will take advantage of this time-limited opportunity to obtain neuroimaging data from participants enrolled in the VA-funded trial to examine PLIÉ’s effect on brain structure and brain function in individuals with AD/ADRD. We will accomplish this by acquiring neuroimaging data from PLIÉ trial participants who are eligible for magnetic resonance imaging (MRI) before and after they undergo 16 weeks of PLIÉ (for 1 hour, 2 days/week) or 16 weeks of Usual Care.

The proposed study is innovative because it leverages the randomize-controlled design and infrastructure of a funded clinical trial to elucidate the neural mechanisms of a novel, non-pharmacological intervention that, in pilot testing, improved cognitive and physical function and quality of life in individuals with AD/ADRD and reduced caregiver burden. Furthermore, the proposed study adds a neuroimaging arm to a funded clinical trial that will not only complement, but may allow for better understanding of the trial’s results (i.e., the proposed study could explain why PLIÉ improves cognition, physical function, and quality of life). We hypothesize that PLIÉ benefits cognitive function by slowing brain atrophy and enhancing brain blood flow and functional connectivity, which in turn, leads to improvements in physical function and quality of life. Not only is PLIÉ a non-invasive and non-pharmacological intervention, but it can be implemented widely in community and home settings at relatively low cost. Thus, it has the potential to address an enormous public health need. The proposed study’s design to explicitly understand the neural mechanisms underlying PLIÉ’s effects will provide valuable information that could be used to enhance the effectiveness and acceptance of this novel dementia treatment that, in pilot testing, improved quality of life in individuals with AD/ADRD and reduced caregiver burden.