Preventing Loss of Independence Through Exercise (PLIÉ) in Persons With Mild Cognitive Impairment (MCI)

Study Overview
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Brief Summary
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Nearly 1 in 10 older Americans have dementia, which is a devastating condition that leads to a progressive loss of independence and functional status. Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. The investigators have developed a novel, integrative exercise program called Preventing Loss of Independence through Exercise (PLIE) that incorporates elements from Eastern and Western exercise modalities and is designed to build and maintain the capacity to perform basic functional movements while increasing mindful body awareness and enhancing social connection. Pilot study results suggest that PLIE is associated with meaningful improvements in physical function, cognitive function and quality of life in individuals with dementia, as well as reduced caregiver burden. The goal of the current study is to perform a randomized, controlled trial to test the efficacy of PLIE in older adults who have MCI but who do not yet have dementia. The investigators will also investigate the neural mechanisms underlying PLIE by acquiring brain imaging measures.

Detailed Description
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The goal of the proposed study is to perform a randomized, controlled trial (RCT) to test the efficacy of a novel integrative exercise program called Preventing Loss of Independence through Exercise (PLIE) on function and quality of life in older adults living in the community with Mild cognitive impairment (MCI), which is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. Because current dementia medications have minimal impact on function and quality of life and do not stop or slow the disease course, it would be desirable if there were an intervention that could prevent or delay the onset of full-blown dementia. Moreover, there is growing evidence that behavioral interventions such as exercise have a variety of beneficial effects in individuals with dementia and MCI. PLIE was developed based on recent discoveries in neuroscience and experimental psychology that have found that, although explicit memory (the ability to consciously recall new information) is impaired in individuals with dementia, implicit memory (unconscious learning that typically occurs through repeated exposure) is relatively preserved. Therefore, PLIE focuses on training procedural memory (unconscious learning of procedures) to build the strength and capacity to perform the movements that are most needed for daily function (e.g., transitioning safely from sitting to standing). In addition, to maximize the benefits of the training, PLIE integrates elements of Eastern and Western exercise modalities to develop mindful body awareness and enhance social connection. The investigators have completed a pilot study of the PLIE program at an adult day center in San Francisco, CA. Results suggest that PLIE was associated with clinically meaningful improvements in cognitive function, physical performance and quality of life as well as reduced caregiver burden when compared with usual care at the facility. The current study will enable the investigators to build on this pilot study results by performing a RCT of PLIE for individuals who have MCI but who do not yet have dementia. Study participants will be randomly assigned to receive the PLIE intervention program (1 hour, 2 days/week, 4 months) or Usual Care (UC) control (standard senior center activities, 1 hour, 2 days/week, 4 months) (N=40, 20/group) using a wait-list design. The co-primary outcomes are 4-month change in physical function (Short Physical Performance Battery, SPPB), cognitive function (Alzheimer's Disease Assessment Scale - cognitive subscale, ADAS-cog) and quality of life (Quality of Life in Alzheimer's Disease, QOL-AD). The investigators will also look at the 4-month change in the following neuroimaging measures: brain volume with structural magnetic resonance imaging (MRI), functional connectivity with resting-state functional MRI, cerebral perfusion with arterial-spin labeled MRI. To account for the wait-list design, all outcomes will be assessed at baseline, 4 months and 8 months. The proposed project will address a critically important health problem related to optimizing functional status and quality of life in older individuals with MCI. The current study will utilize rigorous research methods to test the efficacy of an innovative and promising new program for older adults with MCI. If the program is successful, the investigators will work with VA and community-based organizations to implement PLIE more broadly.

Official Title
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Preventing Loss of Independence Through Exercise (PLIÉ) in Persons With Mild Cognitive Impairment (MCI)

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Behavioral: Preventing Loss of Independence through Exercise (PLIE)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of Mild Cognitive Impairment (MCI) by primary care physician and/or neurologist English language fluency willing to attend PLIÉ classes 2 days/week ambulatory and able to take 2 steps without cane or walker; living in the community in a private home or apartment Exclusion Criteria: Behavioral or physical issues that would be disruptive or dangerous to themselves or others (e.g., active psychosis, drug abuse, severe behavioral issues) Unable to attend 2 PLIÉ classes/week during the study period Physical or mental health condition that would make participation difficult (e.g., active psychosis, limited life expectancy) Contraindications to magnetic resonance imaging (MRI), including claustrophobia severe enough to prevent MRI examination, and presence of ferrometallic objects in the body that would interfere with MRI examination and/or cause a safety risk (e.g., pace makers, implanted stimulators, pumps). Started dementia medication (cholinesterase inhibitor or memantine) in past 3 months Planning to start/change any psychotropic medication during the study period Current participation in another research study

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Study participants will be randomly assigned to receive the PLIE intervention program (1 hour, 2 days/week, 4 months) or Usual Care (UC) control (standard senior center activities, 1 hour, 2 days/week, 4 months) (N=40, 20/group) using a wait-list design. After 4 months, the groups will cross-over. The UC group will receive the PLIE intervention while the first PLIE group will participate in standard senior center activities for 4 months.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLIE<br>PLIE is an integrative exercise program that focuses on training procedural memory for the ability to perform the movements that are most needed for daily function (e.g., transitioning safely from sitting to standing) while increasing mindful body awareness and encouraging social connection. It combines elements from a wide range of Eastern and Western exercise modalities, including occupational therapy, physical therapy, yoga, tai chi, Feldenkrais, Rosen Method, dance movement therapy and mindfulness meditation. | Behavioral: Behavioral: Preventing Loss of Independence through Exercise (PLIE)<br>* PLIE is an integrative exercise program that focuses on training procedural memory for the ability to perform the movements that are most needed for daily function (e.g., transitioning safely from sitting to standing) while increasing mindful body awareness and encouraging social connection. It combines elements from a wide range of Eastern and Western exercise modalities, including occupational therapy, physical therapy, yoga, tai chi, Feldenkrais, Rosen Method, dance movement therapy and mindfulness meditation.<br>|
| No Intervention: Usua Care<br>Study participants who are randomized to the Usual Care (UC) control group will continue to participate in usual activities at the senior center, which include a combination of daily physical, mental and social activities. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Physical Performance Battery (SPPB) | The SPPB was developed by the National Institute on Aging to provide an objective tool for measuring physical performance in older adults. Lower body strength is assessed based on time to complete 5 chair stands without using arms. Balance is assessed based on the ability to hold different stands for 10 seconds, including the side-by-side, semi-tandem and full tandem stands. Mobility is assessed based on usual walking speed over a 3-meter walking course. The total SPPB score is the sum of the 3 component scores and may range from 0 to 12. Prior studies have found that the SPPB is valid and reliable and associated with important outcomes including disability and mortality. A recent systematic review concluded that the SPPB was one of the best tools available to measure physical performance in older adults based on reliability, validity and responsiveness. | baseline to 4 months | 
| Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) | The Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog) is one of the most commonly used outcome measures in dementia drug treatment trials and is one of the measures considered by the Food and Drug Administration for approval of dementia medications. It includes direct assessment of learning (10-word list), naming (objects), following commands, constructional praxis (figure copying), ideational praxis (mailing a letter), orientation (person, time, place), recognition memory and remembering test instructions and is scored on an 80-point scale with higher scores reflecting worse cognitive function. Prior studies have found the ADAS-cog to be valid and reliable with Cronbach's alpha greater than 0.8 and test-retest reliability above 0.9 | baseline to 4 months | 
| Change in Default Mode Network (DMN) functional connectivity, as measured by resting state functional Magnetic Resonance Imaging (rs-fMRI) as quantified by 3 Tesla MR imaging. | The DMN is a network of interacting brain regions known to have activity highly correlated with each other and distinct from other networks in the brain. Evidence has pointed to disruptions in the DMN with people with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). | baseline to 4 months | 
| Change in cerebral perfusion, as measured by arterial spin labeled (ASL) perfusion MRI as quantified by 3 Tesla MR imaging. | Cerebral perfusion pressure measures blood flow to the brain | baseline to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Scale in Alzheimer's Disease (QOL-AD) | The Quality of Life Scale in Alzheimer's Disease (QOL-AD) is a standard quality of life measure that asks parallel questions of affected individuals and caregivers. Current quality of life is rated as poor (1 point), fair (2 points), good (3 points) or excellent (4 points) in 13 areas: physical health, energy, mood, living situation, memory, family, marriage, friends, self as a whole, ability to do chores around the house, ability to do things for fun, money, and life as a whole. Scores may range from 13 to 52 with higher scores reflecting better quality of life. Prior studies have found that the QOL-AD is a valid and reliable measure, with Cronbach's alpha of 0.84 for patient reports and 0.86 for caregiver reports and interrater reliability based on Cohen's kappa values >0.70. | baseline to 4 months | 
| Change in hippocampal subfield volumes as quantified by 3 Tesla MR imaging | Change in the volume of various subfields of the hippocampus, a brain structure critical for learning and memory that is compromised in patients with MCI and AD. | baseline to 4 months |