Paired Integrative Home Exercise for Seniors With Dementia and Their Caregivers (PairedPLIE)
Paired Integrative Home Exercise for Seniors With Dementia and Their Caregivers (PairedPLIE)
Specific Aim 1: To determine feasibility of a 20-minute dyadic exercise program for
 ambulatory individuals with dementia and caregivers living at home based on recruitment,
 adherence and retention. Investigators will conduct a pilot randomized controlled trial (RCT)
 with 20 dyads (total N = 40) in groups of 5 randomized to 16-week group exercise classes and
 regular home practice or wait list in a cross-over design. Investigators will assess
 feasibility of enrollment and retention, the proportion of completed outcome measures, and
 adherence by class attendance logs, caregiver-reported home practice logs and qualitative
 interviews to assess ease of implementation in the home environment. Investigators will
 explore feasibility of weekly phone calls to (potentially overwhelmed) caregivers and Fit-bit
 accelerometers as a measure for tracking home practice.

 Specific Aim 2: To collect preliminary effect size data for sample size calculation for a
 larger trial. Investigators will assess standard outcomes (such as the Short Physical
 Performance Battery and Alzheimer's Disease Assessment Scale - cognitive subscale as primary
 outcomes for affected individuals; and Caregiver Burden Inventory for caregivers) commonly
 used in pharmacological studies of individuals with dementia at baseline, 16 and 32 weeks and
 calculate effect sizes (Cohen's d) for between-group differences in outcome changes in the 20
 dyads of the RCT described in Specific Aim 1.

 Specific Aim 3: To explore the feasibility of using non-invasive Near-Infrared Spectroscopy
 (NIRS) to assess regional cortical brain oxygenation and its sensitivity to change.
 Investigators will compare brain oxygenation variations before and after the exercise
 intervention during a memory task for the seniors with dementia.
Alzheimer's dementia (AD) is a major public health challenge for our century. Research into
 pharmaceutical therapies has been disappointing and not provided any safe medications that
 can halt the disease's trajectory of decline in the cognitive, functional, emotional and
 social capabilities of the affected individuals. For non-pharmacological approaches,
 multi-domain exercise programs that address several of these capabilities in an integrated
 way have shown strong promise for their ability to slow the decline. The team of
 investigators has systematically developed one such program-the Preventing Loss of
 Independence through Exercise (PLIÉ) program-an integrative exercise program that uses
 procedural memory (memory for movements without explicit recall), can be taught at and
 integrated into senior day care centers and has been pilot-tested by our team with
 encouraging results for functional, cognitive and social outcomes (see Table 1).

 However, (1) most people in the community do not have access to a day care center, are
 concerned about the stigma associated with day care or are unable to afford it. This was
 endorsed by semi-structured interviews conducted with caregivers and community-based
 organizations in preparation for a larger study of the PLIÉ program. There is a huge need for
 innovative programs to assist individuals with dementia and their caregivers in the
 community. Irrespective of having access to day care or not, motivated caregivers, who are
 aware of the benefits of exercises for their loved ones and spend hours alone with them at
 home, ask: "What can we do with our [e.g. mother]?" They point out a major lack of guidance
 for caregivers in the community to be able to use a regular exercise practice on a long-term
 basis at home. Caregivers and seniors with dementia living together in the community are
 dyads in need of a paired exercise program. (2) How exercise may delay cognitive and
 functional decline is unknown. One hypothetical mechanism of action is an improved brain
 oxygenation related to exercise. Near-Infrared Spectroscopy (NIRS) is a non-invasive method
 to assess regional cortical oxygenation levels, has been suggested for the early diagnosis of
 Alzheimer's dementia, but has never been applied to longitudinal studies in this population.

 Paired home exercise programs for seniors with dementia and their primary caregivers have
 rarely been studied. A pilot study that used 6 'sticky hands' movement variations based on
 Tai Chi, music and exercise incentives found improvements in 2 outcome measures considered to
 be important in fall prevention (sit-to-stand time, one-legged stance time). However,
 movements were limited to tai chi and outcomes to fall-related function, leaving out
 cognitive function for which the PLIÉ program had shown such promising results.

 The group of investigators is an established collaboration between the Osher Center for
 Integrative Medicine and the Department of Psychiatry at UCSF and has recently pioneered a
 novel, 45-minute, multi-domain program called Preventing Loss of Independence through
 Exercise (PLIÉ) that integrates physical activity (training of procedural memory for basic
 daily activities such as sitting and standing), cognitive stimulation (mindful body
 awareness), social engagement (group movement and sharing of in-the-moment experiences), and
 caregiver education (monthly home-visit). The investigators pilot-tested PLIÉ in 11
 individuals with mild to moderate dementia who were attending an adult day program at the
 Institute of Aging in San Francisco, CA (ClinicalTrials.gov registered NCT01371214), and
 found (Table 1) preliminary evidence of medium to large, clinically meaningful effect sizes
 com-pared to usual care (UC; 45 minutes of usual chair-based exercises at the day care
 center) across a wide range of out-comes including measures of quality of life (0.83),
 cognitive function (0.76), physical performance (0.34) and caregiver burden (0.49).7,11 That
 study methodologically mimicked a drug study by including measures that are commonly used in
 dementia medication trials, which enabled comparison of the magnitude of our results to
 currently available dementia medications.. The investigators are now completing data
 collection for a second implementation of the PLIÉ program at an adult day program in San
 Rafael, CA (Senior Access). The intervention of the current proposal will be similar to PLIÉ
 in using the same principles6 and taught by instructors trained in the PLIÉ program. However,
 it will differ in its format: instead of a day-care center-based group program taught by
 professional exercise instructors, it uses a dyadic approach, introduced through caregiver
 support groups to pairs of individuals with dementia and their caregivers, initially using a
 group class format, but taught to enable caregivers to practice independently at home. To
 allow for wide-spread long-term routine application, it will be brief (20 minutes), use
 personalized music associated with positive affect memories, and be supported by video
 instructions.

 2 papers have been published about the study.

 Therefore, the investigators propose studying a paired integrative exercise intervention that
 can be practiced in dyads of caregivers and affected individuals at home or in a
 community-based support group environment, does not require additional equipment, can be
 easily learned by caregivers, and may ameliorate the impact of dementia for older persons and
 caregivers. The investigators suggest a multimodal program that is based on implicit
 procedural learning and the integrative principles of the PLIÉ program: it includes physical
 (through touch) and social interaction with a trusted family member, focuses on physical
 function such as balance, includes personalized music choices and singing, supports positive
 affect, and uses language to cognitively enhance the experience of mind-body integration. It
 promotes a playful, non-judgmental supportive attitude to foster a sense of embodied
 personhood in individuals with dementia through joyful social interaction with an empowered
 caregiver.

 1. Recruitment. Study participants will be recruited from local caregiver support groups of
 Kaiser Permanente in Oakland. Exercise instructors and the PI have already been invited
 to give presentations at their regular meetings. Contacts have been established with 3
 caregiver support groups meeting at Kaiser Permanente in Oakland, totaling about 100
 caregivers, who meet once a month and confirmed strong interest to participate. Thus, it
 is highly likely that we will twice be able to recruit 10 dyads of eligible
 participants. In addition, investigators will give study flyers to caregiver support
 managers at Kaiser Permanente, the local Alzheimer's Association groups, and the
 Alzheimer's Services of the East Bay (ASEB). In addition, we will recruit at ASEB.

 Caregivers will be informed about the study by brief presentations by the PI and an
 exercise instructor during regular support group meetings. A flyer will be handed to
 interested potential participants describing the study and providing an opportunity to
 learn more by returning a form or calling the research study staff. Those caregivers who
 express interest will be contacted by research staff by phone to further assess
 interest/eligibility and to schedule a consent visit.

 2. Informed consent. Verbal consent to be screened will be obtained over the telephone
 prior to collecting information on demographics and medical and psychiatric history.
 Written consent will be obtained with the affected individuals and caregivers together,
 as described in more detail below. The consent forms will be reviewed and capacity to
 consent will be assessed in primary participants based on responses to questions to
 determine level of understanding of study procedures, risks, benefits and rights.
 Participants who do not demonstrate capacity to consent will be asked to assent to study
 procedures and caregivers will be asked to consent on their behalf. A separate consent
 form will request permission to participate in video recording of exercise classes for
 quality control purposes. After the consent process has been completed, the Modified
 Mini-Mental State Exam (3MS) will be administered to affected individuals to assess
 level of cognitive impairment. Consent procedures will take place at the Kaiser group
 room unless otherwise requested by caregivers.

 If the caregiver is not the Legally Authorized Representative (LAR) or the legal
 guardian of the affected individual, the screening interview will be stopped.
 Investigators will then mail a letter to the LAR or legal guardian and invite her/him to
 contact us by mail or phone to discuss the study and the consent process. The screening
 and eligibility questions for the affected individual will then be completed with the
 LAR or legal guardian. If investigators do not get a response within 2 weeks they will
 call the LAR or legal guardian by phone assuming that she/he has received our letter.
 Only if this person permits the affected individual's study participation investigators
 will contact the caregiver and the affected individual again.

 How will investigators assess the potential participant's capacity to consent? Capacity
 to consent will be assessed by research assistants (RA) who will be extensively trained
 by the PI and co-investigators using a standardized procedure. Investigators first
 provide the consent form to the patient and caregiver together and allow them to review
 it. RAs then describe the key points of the form, pointing to the areas on the form
 where the information is described in more detail. They then ask a series of yes/no
 questions to assess understanding of the information in the form. If the participant
 cannot answer the questions, RAs review the material again and point to the section on
 the form. Investigators then repeat the questions. If participants are unable to answer
 all of the questions on their own after review, RAs consider them to lack capacity to
 consent. RAs then ask them if they would like to participate in the study to obtain
 their assent. RAs say that they are going to ask the caregiver to sign the form on the
 participant's behalf to obtain written consent. Most of the team's research assistants
 have been and are psychology graduate students who are highly sensitive to working with
 vulnerable patients. Investigators train new research staff by having them role play the
 consent process until senior personnel determine that they are adequately prepared. They
 then observe senior personnel performing the consent process on at least one study
 participant. Subsequently they are observed performing the consent process until senior
 personnel determine that they are competent. Investigators/RAs also have weekly team
 meetings to discuss any difficulties that arise during consent or any other study
 procedure.

 Randomization: Following the baseline assessments, assessing staff will open an opaque,
 sealed envelop for each dyad (affected individual and caregiver). Envelops will be
 numbered and will contain the group assignment. A statistician not involved in the study
 will prepare these envelops and create a random sequence of numbers using a computer
 program. There will be 2 piles of envelops, one for men and one for women to recruit a
 similar proportions of male and female participants in both groups.

 3. 1st Pilot-test Phase. Affected individual/caregiver dyads who consented will be invited
 to participate in the first pilot phase of 10 dyads. These subjects will participate in
 either Group 1 (initial intervention), which will participate first, or Group 2 (wait
 list control group). Group 1 will participate in the Paired PLIÉ program 2 times/week
 for 45 minutes for 4 weeks and then once/month for additional 3 months while Group 2
 will be wait-listed. After Group 1 has completed their training, Group 2 will
 participate in the PLIÉ program 2 times/week for 45 minutes for 4 weeks and then
 once/month for additional 3 months. Group assignment will be random. Investigators will
 strive to have an equal distribution of men/women in the two groups.

 Intervention: the exercise protocol is based on the PLIÉ protocol, which the
 investigators have developed in consultation with experts worldwide who have experience
 performing different types of exercises in individuals with mild-to-moderate dementia,
 including traditional strength-building exercises, yoga, Tai Chi and Feldenkrais.
 Specifically, investigators have identified exercises from each of these traditions that
 engage the muscles most needed to maintain independence--including lower body strength
 (to help with getting out of bed/chair), balance (to minimize risk of falls), upper body
 strength (to help with lifting), fine motor exercises (to help with activities such as
 eating and brushing teeth), and pelvic floor exercises (to help with continence)--and
 have combined them into a unique integrative exercise program. These exercises are
 designed to be purposeful (i.e., to achieve a goal) and to build procedural ('muscle')
 memory. In addition, breathing and guided meditation exercises are included to promote
 relaxation and well-being.

 While the PLIÉ program has been tested in a senior day care setting, investigators are
 combining these exercises in a new way, that they can be practiced at home in dyads of
 affected individuals and caregivers.

 4. 2nd Pilot-test Phase. In a second phase investigators will repeat the identical protocol
 and intervention with 10 more dyads of affected individuals and caregivers.

 5. Pre- and post-intervention assessment. Investigators will perform a variety of standard
 measures in all participants and caregivers. The following assessments will occur at
 baseline and after the 3 follow-up months. They will primarily be utilized to assess
 feasibility and logistics of data collection procedures. Separate appointments will be
 made for affected individuals and caregivers to maximize the validity of data collected
 (e.g., to ensure that caregivers do not 'help' affected individuals with answers to
 questions and feel comfortable providing information about issues such as difficult
 behaviors or levels of stress). Affected individuals assessments will take place at the
 group room. The initial caregiver assessment will take place at the caregiver's home or
 the group room. The first line of communication for follow-up appointments will be via
 telephone or in person to minimize the risk of loss of privacy. At the caregiver
 participant's request, further communication may be conducted via mail, email, fax or
 text. Caregivers will be informed that these modes of communication may increase their
 risk of loss of privacy. Mail, email, fax and text communications will include a
 confidentiality statement. The minimum amount of identifying information will be
 included in all communications. Study forms will include unique study ID numbers only.
Inclusion Criteria:

 -  Affected individuals: dementia diagnosis (any type, mild to moderate severity [defined
 as independent in at least 1 basic ADL])

 -  Ambulatory and able to take 2 steps without cane or walker

 -  Living in the community in a private home or apartment

 -  English language fluency.

 -  Caregiver/care partner: lives with affected individual

 -  Motivated to practice regularly (4-5 times per week) at home

 -  Able to answer study questions related to the affected individual's functional status,
 mood, behaviors, quality of life and their own feelings regarding caregiving

 -  English language fluency.

 Exclusion Criteria:

 -  Affected Individuals: behavioral or physical issues that would be disruptive or
 dangerous to themselves or others (e.g., active psychosis, drug abuse, severe
 behavioral issues)

 -  Planning to move to a facility before the end of the study period

 -  Terminal illness (life expectancy < 1 year)

 -  Non-stable dementia medication dose

 -  Current participation in another research study.

 -  Caregiver/care partner: planning to place affected individual in an institutional
 setting during the study period

 -  Terminal illness (life expectancy < 1 year)

 -  Behavioral or physical issues that are disruptive or dangerous.