Posted December 27, 2022

Linda Chao, Ph.D., Northern California Institute for Research and Education

There is a desperate need for alternative, non-pharmacological therapies that improve overall health, cognition, and quality of life for individuals with cognitive decline, mild cognitive impairment (MCI), Alzheimer's disease (AD)/AD-related dementia (ADRD), and their caregivers. This is especially true for our military Service Members and Veterans, as risk factors such as traumatic brain injury (TBI), vascular disease, and alterations in lifestyle and cognition occur in military personnel at higher rates and greater severity than the general public.^1-2 Even so, individuals whose voices are most important, such as those affected by cognitive decline and their caregivers, are often left out of the discussion across the research to clinical care pipeline. Dr. Linda Chao and her team are addressing these important issues with funding from the Peer Reviewed Alzheimer's Research Program (PRARP) within the Congressionally Directed Medical Research Programs (CDMRP). Dr. Chao recently received a Fiscal Year 2020 (FY20) PRARP Leveraging Approaches for Innovation in Care and Support Award (Award # W81XWH-21-1-0147) to establish the Moving Online Together Investigation Of Neurocognition (MOTION) study for older adults with MCI and their caregivers.

Preventing Loss of Independence through Exercise (PLI�): a Mind-Body Intervention to Fight Against Cognitive Decline

The MOTION study builds on two previous studies using the innovative Preventing Loss of Independence through Exercise (PLI�) intervention, in which participants are guided in a group exercise program that uses key principles for procedural learning, functional movement, goal orientation, mindfulness, breathing, positive emotions, and social interaction. The first was a small, non-Department of Defense pilot study that used the original iteration of PLI� (n=12), in which clinically meaningful improvements in physical performance, cognitive function, and quality of life for both participants with AD/ADRD and their caregivers were observed compared to individuals receiving standard care.³ The second was a larger study of PLI� implemented by Dr. Chao and her team, with an FY16 PRARP Quality of Life Research Award (Award # W81XWH-17-1-0490). This study also took advantage of a Department of Veterans Affairs-funded randomized controlled trial of PLI� for individuals with AD/ADRD, incorporating and analyzing neuroimaging measures from these participants. Interestingly, individuals with MCI that participated in PLI� showed improvements in functional connectivity in the default mode network, cognition, interoceptive self-regulation, well-being, and reduced feelings of social isolation.⁴

The current MOTION study includes telehealth delivery of a randomized clinical trial that directly compares the effects of PLI� to other mind-body interventions (Tai Chi Chih [TCC]) or a health and wellness educational program (HEW) in older adults with MCI. Additionally, the MOTION study will investigate the neural mechanisms underlying the effects of mind-body interventions in people with MCI through in-person follow-up assessments. Older adults with an MCI diagnosis will be recruited to the clinical trial and randomized into one of three treatment groups: (1) telehealth-delivered PLI�, a group movement program that trains procedural memory for basic functional movements (e.g., sit-to-stand), increases mindful-body awareness, and facilitates social connection; (2) telehealth-delivered TCC that includes exercise and mediation; and (3) a telehealth-delivered HEW control in which participants watch videos about topics related to health and wellness. After 12 weeks of participation in the intervention, all participants will undergo behavioral and neuroimaging assessments, and they will also undergo additional behavioral assessments after 36 weeks of participation. The neuroimaging measures include examining functional connectivity between limbic brain regions important for cognition and memory, cortical thickness, metabolism, pathology, and white matter imaging.

MOTION Study: Leveraging Community Partners for Better Research Outcomes and Engagement

One of the most important aspects of Dr. Chao's MOTION study is the use of community-based participatory research approaches that engage the affected community. Dr. Chao has emphasized this, noting that �our collaboration with our community partner, Together Senior Health (TSH) has been invaluable. TSH is offering �Moving Together,� a unique program that is designed specifically for our study population of older adults living in the community with mild cognitive impairment.� TSH is a community-based information technology company that delivers livestreaming mind-body group programs to people living with memory loss/ADRD (previously supported by a National Institutes of Health Small Business Innovative Research grant).⁵ TSH will be integral for recruitment, will deliver all three interventions, and will livestream the tele-PLI� and tele-TCC classes for the MOTION study (refer to Figure 1). In addition to targeted outreach through assisted-living facilities, retirement homes, and clinics, the study will also lean heavily on the Los Angeles County Department of Mental Health Services for older adults, an outreach program, which should help the study recruit minority participants.

Figure 1: TSH Telehealth platform for intervention delivery with video streams and chat functionality. (Figure Provided)

The telehealth nature of the MOTION study and accessibility of the livestreaming platform to older adults with cognitive decline is a key feature that will increase scalability and accessibility of these non-pharmacological interventions, which is especially important given the ongoing global health crisis of the COVID-19 pandemic. Together, these approaches also support the overall goal and new mandate of the PRARP at CDMRP, in which all new clinical applications FY22 and beyond must include at least one person with lived AD/ADRD experience into the research team as a project advisor throughout the planning, implementation, and dissemination of the research project. PRARP is leveraging this requirement in future years to center collaborative research approaches such as community-based participatory research. This approach will give an important seat at the table to the affected community and, most importantly, gives those with TBI, AD/ADRD, MCI, and dementia and their caregivers access to active researchers and clinicians, spurring new possibilities in guiding research programs and improving patient advocacy.

References:

¹Gardner RC and Yaffe K. 2015. Epidemiology of mild traumatic brain injury and neurodegenerative disease. Mol Cell Neurosci 66(Pt B):75-80. doi: 10.1016/j.mcn.2015.03.001. Epub 2015 Mar 5. PMID: 25748121; PMCID: PMC4461453.

²Zhu CW and Sano M. 2021. Demographic, health, and exposure risks associated with cognitive loss, Alzheimer's disease and other dementias in US military veterans. Front Psychiatry 12:610334. doi: 10.3389/fpsyt.2021.610334. PMID: 33716816; PMCID: PMC7947283.

³Barnes DE, Mehling W, Wu E, et al. 2015. Preventing loss of independence through exercise (PLI�): a pilot clinical trial in older adults with dementia. PLoS One 10(2):e0113367. doi: 10.1371/journal.pone.0113367. PMID: 25671576; PMCID: PMC4324943

⁴Chao LL, Lee JA, Martinez S, et al. 2021. Preventing loss of independence through exercise (PLI�): A pilot trial in older adults with subjective memory decline and mild cognitive impairment. J Alzheimers Dis 82(4):1543-1557. doi: 10.3233/JAD-210159. PMID: 34180414; PMCID: PMC8461710.

⁵News article about the NIH SBIR supporting TSH PLIE platform and recruitment information

Links:

Public and Technical Abstracts: MOTION: Moving Online Together Investigation of Neurocognition

Public and Technical Abstracts: Using Multimodal Imaging to Examine the Neural Mechanisms of an Integrative Exercise Program for Individuals with Dementia

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