Modulation Effects of a Novel Body-mind Intervention on Subjective Cognitive Decline
Phase: NA
Conditions: Cognitive Decline
Sponsor: Arizona State University

 
 
Modulation effects of a novel body-mind intervention 
on subjective cognitive decline  
Protocol Number: 06222022 
National Clinical Trial (NCT) Identified Number:  NCT05446909 
Principal Investigator: Yi-Yuan Tang, Ph.D. 
Sponsor: Arizona State University 
Grant Title: Modulation effects of a novel body-mind intervention on subjective 
cognitive decline 
Grant Number: R61AT010138-02S1 
Funded by:  National Center for Complementary and Integrative Health 
Version Number:  v.1.1 
2022-06-22 
 
Summary of Changes 
Version 
Date 
1.0 
2022-02-10 
1.1 
2022-06-22 

Based on the NIH Protocol Template for Behavioral and Social Sciences Research Involving Humans 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

Preventing Cognitive Decline 
 
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 3 
1.3 
Schedule of Activities .......................................................................................................................... 5 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Rationale .................................................................................................................................... 6 
2.2 
Background ........................................................................................................................................... 6 
2.3 
Risk/Benefit Assessment .................................................................................................................... 6 
2.3.1 
Known Potential Risks ..................................................................................................... 6 
2.3.2 
Known Potential Benefits ................................................................................................ 7 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 7 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ............................................................................................................................................. 8 
4.1 
Overall Design ...................................................................................................................................... 8 
4.2 
Scientific Rationale for Study Design ................................................................................................ 9 
4.3 
Justification for Intervention ............................................................................................................... 9 
4.4 
End-of-Study Definition ....................................................................................................................... 9 
5 
STUDY POPULATION .................................................................................................................................. 9 
5.1 
Inclusion Criteria .................................................................................................................................. 9 
5.2 
Exclusion Criteria ................................................................................................................................. 9 
5.3 
Lifestyle Considerations ...................................................................................................................... 9 
5.4 
Screen Failures .................................................................................................................................. 10 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 10 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 10 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 10 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 10 
6.1.2 
Administration and/or Dosing ....................................................................................... 11 
6.2 
Fidelity ................................................................................................................................................. 11 
6.2.1 
Interventionist Training and Tracking .......................................................................... 11 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 11 
6.4 
Study Intervention/Experimental Manipulation Adherence .......................................................... 12 
6.5 
Concomitant Therapy ........................................................................................................................ 12 
6.5.1 
Rescue Therapy ............................................................................................................. 12 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 12 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 12 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 12 
7.3 
Lost to Follow-Up ............................................................................................................................... 13 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................................................... 13 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 13 
8.2 
Safety Assessments .......................................................................................................................... 13 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 14 
8.3.1 
Definition of Adverse Events ........................................................................................ 14 
8.3.2 
Definition of Serious Adverse Events .......................................................................... 14 

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8.3.3 
Classification of an Adverse Event .............................................................................. 14 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 15 
8.3.5 
Adverse Event Reporting .............................................................................................. 15 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 16 
8.3.7 
Reporting Events to Participants ................................................................................. 16 
8.3.8 
Events of Special Interest ............................................................................................. 16 
8.3.9 
Reporting of Pregnancy ................................................................................................ 16 
8.4 
Unanticipated Problems .................................................................................................................... 16 
8.4.1 
Definition of Unanticipated Problems .......................................................................... 16 
8.4.2 
Unanticipated Problems Reporting .............................................................................. 17 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 17 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 17 
9.1 
Statistical Hypotheses ....................................................................................................................... 17 
9.2 
Sample Size Determination .............................................................................................................. 18 
9.3 
Populations for Analyses .................................................................................................................. 18 
9.4 
Statistical Analysis Plan .................................................................................................................... 18 
9.4.1 
General Approach .......................................................................................................... 18 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 18 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 19 
9.4.4 
Safety Analyses .............................................................................................................. 19 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 19 
9.4.6 
Planned Interim Analyses ............................................................................................. 20 
9.4.7 
Sub-Group Analyses ..................................................................................................... 20 
9.4.8 
Tabulation of Individual Participant Data .................................................................... 20 
9.4.9 
Exploratory Analyses ..................................................................................................... 20 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 20 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 20 
10.1.1 
Informed Consent Process ........................................................................................... 20 
10.1.2 
Study Discontinuation and Closure ............................................................................. 21 
10.1.3 
Confidentiality and Privacy ........................................................................................... 21 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 22 
10.1.5 
Key Roles and Study Governance .............................................................................. 22 
10.1.6 
Safety Oversight ............................................................................................................. 22 
10.1.7 
Clinical Monitoring .......................................................................................................... 23 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 23 
10.1.9 
Data Handling and Record Keeping ............................................................................ 24 
10.1.10 
Protocol Deviations ........................................................................................................ 24 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 25 
10.1.12 
Conflict of Interest Policy .............................................................................................. 25 
10.2 
Additional Considerations ................................................................................................................. 25 
10.3 
Abbreviations and Special Terms ................................................................................................... 25 
10.4 
Protocol Amendment History ........................................................................................................... 27 
11 
REFERENCES ............................................................................................................................................. 28 
12 
ATTACHMENT ............................................................................................................................................. 32 
 

Preventing Cognitive Decline 
 
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1 
STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB for review and approval. Approval of both the protocol and the consent 
form(s) must be obtained before any participant is consented. Any amendment to the protocol 
will require review and approval by the IRB before the changes are implemented to the study. All 
changes to the consent form(s) will be IRB approved; a determination will be made regarding 
whether a new consent needs to be obtained from participants who provided consent, using a 
previously approved consent form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
03-18-2024 
 
Name: Yi-Yuan Tang 
 
 
Title: Professor  
 
Investigator Contact Information 
Affiliation: Arizona State University 
Address: 425 N 5th St, Phoenix, AZ 85004  
Telephone: 4807903577 
Email: yiyuan@asu.edu 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
 
Title: 
Modulation effects of a novel body-mind intervention on subjective 
cognitive decline 
Grant Number: 
R61AT010138-02S1 
Study Description: 
The study aims to understand the mechanisms and training effects of 
evidence-based body-mind training on improving cognitive performance 
and preventing cognitive decline. Specifically, it aims to investigate the 
modulation effects of a novel body-mind intervention on subjective 
cognitive decline (SCD) using an evidence-based preventive 
intervention - integrative body-mind training (IBMT). 
Objectives: 
 
Primary Objective: This study aims to investigate the modulation effects 
of a novel body-mind intervention on behavioral and cognitive 
outcomes. 
Secondary Objectives: This study aims to investigate the modulation 
effects of a novel body-mind intervention on brain outcomes. 
Endpoints: 
Primary Endpoint: Behavioral and cognitive outcomes 
Secondary Endpoints: Brain outcomes 
Study Population: 
40 adults (both sexes) between the age 40-65 years old with SCD in the 
Phoenix, AZ area. 
Phase or Stage: 
N/A  
Description of 
Sites/Facilities Enrolling 
Participants: 
The participating site/facility is Arizona State University, where 
enrollment of participants happens. There is no foreign site.  
Description of Study 
Intervention/Experimental 
Manipulation: 
Experimental manipulation is evidence-based preventive intervention - 
integrative body-mind training (IBMT) and will be offered as a group 
for 10 sessions. 
Study Duration: 
12 months 
Participant Duration: 
3 months 
1.2 
SCHEMA  
 
 
 

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Figure 1. Flowchart of screening, inclusion, and assessment process 
 
Screening 
 
 
 
Visit 1 
Day 1 
 
 
 
 
 
 
 
 
 
 
 
 
Visits 2-11 
Day 3 ± 1 to  
Day 12 ± 1 
 
 
 
Visit 12 
Day 13 ± 2 
 
 
 
Visit 13 
Day 90 ± 2 
 
 
Total N: 40 
Screen potential participants by inclusion and exclusion criteria; schedule Visit 1. 
Conduct informed consent process. Perform baseline assessments. 
 
Details refer to Section 1.3, Schedule of Activities 
Follow-up assessments 
Details refer to Section 1.3, 
Schedule of Activities 
Arm 2 
N = 20  
Arm 1 
N = 20  
Administer study intervention Session 1 to Session 10 
Randomize 
Post-Intervention assessments 

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1.3 
SCHEDULE OF ACTIVITIES  
 
 
 
 
Screening 
 
 
Visit 1 
Day 1 
Visit 2 to Visit 
11 
Day 3 ±1 to Day 
12±1 
Visit 12 
 Day 13 ±2 
Visit 13 
Day 90 ±2 
Review Eligibility 
X 
 
 
 
 
Informed Consent 
 
X 
 
 
 
Demographics 
 
X 
 
 
 
Outcome Evaluation 
 
 
 
 
 
Behavioral Assessment 
(Emotion Regulation 
Questionnaire; Five Facet 
Mindfulness 
Questionnaire; Subject 
Cognitive Decline 
Questionnaire) 
 
X 
 
X 
X 
Brain Assessment (MRI 
scan) 
 
X 
 
X 
X 
Randomization 
 
X 
 
 
 
Control & Experimental Interventions  
 
X 
X 
 
 
Adverse Events Reporting 
 
X 
X 
X 
X 

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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
More than five million people in the US have Alzheimer’s Disease (AD), at a cost to society of more than 
$200 billion per year. However, available preventions and treatments have limited efficacy. It is imperative 
to develop evidence-based programs to help promote cognitive functioning in older adults. We propose 
to address this urgent and critical public health issue by examining the effectiveness of a brief evidence-
based mindfulness intervention – Integrative Body-Mind Training (IBMT) in old adults with SCD through 
randomized clinical trials (RCTs). We will examine if the intervention can improve behavioral and cognitive 
functioning, as well as brain changes in these older adults. Outcomes from this study will inform 
prevention and treatment option to promote health and well-being for individuals with SCD, MCI, and 
ADRD. 
2.2 
BACKGROUND  
Subjective cognitive decline (SCD), the self-reported perception of memory or cognitive problems, is a risk 
factor for the development of clinical cognitive decline such as MCI and ADRD. Since SCD manifests prior 
to the onset of clinical impairment, it might provide an optimal stage of time at which to intervene with 
preventive therapies for ADRD before the progressive neurological loss and irreversible cognitive 
impairment.49-52 Recently, few mind-body interventions such as Tai Chi and mindfulness suggested 
promising effects in preventing cognitive decline. However, these interventions often require longer 
training time to achieve modest benefits, making them less optimal for old adults to rapidly learn and 
achieve desirable outcomes.53-63 Thus, choosing short-term effective interventions in improving targeted 
outcomes is highly critical for this time-sensitive aging cohort. Moreover, most mindfulness studies on 
cognitive decline are cross-sectional, which are highly susceptible to confounds and noises. 73-75. Previous 
SCD studies showed brain functional and structural abnormalities are associated with clinical progression 
and annual decline on executive functioning, attention, memory, and global cognition. 66-72. Self-control 
and attention deficits can be improved through brief intervention. Our preliminary RCTs in healthy adults 
provide support for our clinical trial by showing improvement in self-control, attention, cognitive 
functioning, emotion, stress reduction, and quality of life following brief IBMT intervention, 1-45 suggesting 
its potential effectiveness in older adults with SCD. 
2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
The study includes behavioral, cognitive, and brain assessments, as well as mindfulness-based 
intervention. 
Behavioral and Cognitive Assessments 
• 
Immediate risks: Potential boredom from completing the questionnaires and interviews.  
• 
Long-term risks: Data including self-report, questionnaires and interview involve risk of breaches 
in confidentiality. 
• 
Alternative procedures: There are no other available alternative procedures to assess behavior and 
cognition, since to assess the behavior and cognition, we have to use the actual assessments. To 
minimize immediate risks, breaks in between questionnaires and interviews are offered to reduce 

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boredom. To minimize long-term risks, all information about the specific individuals will be 
maintained as confidential. Absolutely no names of subjects are used in published reports or in 
presentations in scientific meetings. All data will be kept in locked files and digital media in the PI’s 
laboratory. Reference to individual subject data will be made with a number and letter code for 
each subject. Any risks to participants are minimal and are outweighed by the benefits of 
increasing our scientific understanding of improving cognitive function in older adults. 
Brain Assessments 
• 
Immediate risks: Potential boredom from completing the MRI scan, the possibility of becoming 
uncomfortable in the enclosed space of the scanner. 
• 
Long-term risks: MRI data involves risk of breaches in confidentiality. 
• 
Alternative procedures: There are no other available alternative procedures to brain, since to 
assess the brain, we have to use the actual MRI assessments.  
 
Mindfulness-based Intervention 
• 
Immediate risks: Potential boredom from completing the intervention.  
• 
Long-term risks: No known risk based on our previous studies 1-12. 
• 
Alternative procedures: There are no other available alternative procedures, since the goal is to 
test the effects of the mindfulness-based intervention. To minimize immediate risks, breaks during 
the session are offered to reduce boredom.  
2.3.2 KNOWN POTENTIAL BENEFITS  
Immediate potential benefits 
The immediate potential benefits from participant in this study include that participants generally 
find the experimental paradigms enjoyable (i.e. meditation state) during the intervention sessions 
2, 19-21.  
Long-term potential benefits 
The long-term potential benefits include that participants have the opportunity to learn more 
about approaches and methods of improving attention, cognition, emotion and quality of life 
during the intervention and may be able to apply the learned knowledge in their everyday life.  
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
Because this is a study that examines the effects of an intervention on behavior, cognition, and behavior, 
it is inevitable to expose participants to risk of boredom during their assessments and interventions, as 
these assessments and intervention are necessary for us to evaluate the effects of the intervention.  
 
To minimize immediate risks of potential boredom from completing the behavioral and cognitive 
assessments, brain assessments, and mindfulness-based intervention, breaks during the assessments and 
interventions are offered to reduce boredom and give participants time to rest. To minimize long-term 
risks, all information about the specific individuals will be maintained as confidential. Absolutely no names 
of subjects are used in published reports or in presentations in scientific meetings. All data will be kept in 
locked files and digital media in the PI’s laboratory. Reference to individual subject data will be made with 
a number and letter code for each subject.  

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Based on the risks of boredom and breach in confidentiality, as well as our approaches to minimize these 
risks, we conclude that any risks to participants are minimal and are outweighed by the benefits of 
increasing our scientific understanding of improving cognitive function in older adults, as well as the 
benefits of potentially having the participants learning ways to improve attention, cognition, emotion and 
quality of life in their everyday life. 
3 
OBJECTIVES AND ENDPOINTS  
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
This study aims to investigate 
the modulation effects of a 
novel body-mind intervention 
on behavioral and cognitive 
outcomes. 
 
 
 
 
Baseline and post-
intervention 
assessments of 
behavioral and 
cognitive 
outcomes 
(emotion 
regulation, 
mindfulness, SCD). 
The novel body-mind 
intervention should lead to 
improvement in behavioral 
and cognitive outcomes at 
post-intervention compared to 
baseline. 
Secondary 
 
 
This study aims to investigate 
the modulation effects of a 
novel body-mind intervention 
on brain outcomes. 
Baseline and post-
intervention 
assessments of 
brain outcomes 
(white matter, 
grey matter, 
functional 
connectivity in AD 
signature regions. 
 
The novel body-mind 
intervention should lead to 
improvement in brain 
outcomes at post-intervention 
compared to baseline. 
Tertiary/Exploratory  
 
 
N/A 
N/A  
 
 
N/A   
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
The study is a randomized control trial (RCT) involving two groups – IBMT (Arm 1: experimental 
manipulation) and health education (HE) (Arm 2: control group) group. Participants in each group will 
be assessed at baseline, post-intervention, and at 3-month follow-up using behavioral, cognitive, and 
brain assessments as described in Section 1.3. Automatic randomization will be conducted by study 
staff and used to assign participants to each arm/group condition using an algorithm before the 
baseline assessment. This randomization procedure ensures balance between groups on gender while 
also balancing total treatment numbers.  

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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
To evaluate the effects of our experimental manipulation, we need an active control group for this RCT 
study design. The HE has been used as a control condition in many previous published studies and is an 
accepted control intervention. Thus, we use it as a control condition in our study design. There are no 
known or potential problems associated with the control group. 
4.3 
JUSTIFICATION FOR INTERVENTION 
The chosen 10-sessions of experimental manipulation - IBMT has been shown to improve behavior, 
cognition, and brain in previous RCTs in healthy adults. Thus, we choose to use the same setup and design, 
and expect the same length and frequency of the intervention would be appropriate for older adults.  
4.4 
END-OF-STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed the baseline 
assessment, 10 intervention sessions, post-assessment, and 3-month follow-up assessment.  
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
1. Provision of signed and dated informed consent form 
2. Males and females; Age 40-65 years old. 
3. Able to read/understand English 
4. Normal performance using standardized cognitive tests 
5. Self-reported decline in cognitive capacity such as memory loss 
6. Eligible for non-invasive fMRI 
7. Willing to be randomized 
8. Free of any severe psychiatric diagnoses or medication that may affect participation 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
1. Medical disorders or medications that affect the central and autonomic nervous system; or a 
positive pregnancy test result (females) 
2. Unable to provide consent or understand study procedures due to mental illness or cognitive 
limitations 
3. Previous meditation experiences 
4. Evidence of illicit drug use 
5. Metal or metallic materials in the body such as pacemaker 
 
5.3 
LIFESTYLE CONSIDERATIONS 

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N/A 
 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently assigned to the study intervention or entered in the study. Individuals who do not meet the 
criteria for participation in this trial (screen failure) because of meeting one or more exclusion criteria that 
are likely to change over time may be rescreened. Examples include the successful removal of metal 
devices that previously made them ineligible for an MRI scan. Rescreened participants will be assigned 
the same participant number as for the initial screening. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
We anticipate to enroll 40 participants (males and females) ages from 40 to 65 years old across different 
race and ethnicity based on local demographic characteristics. Subjects will be recruited through print and 
media ads within local community. This will include radio and online ads and recruitment through social 
media. Flyers will be distributed throughout the local community. Based on our and other’s previous  
experiences in longitudinal studies, about 5-10% of participants will dropout over the study period  
due to illness or relocation. We plan a dropout rate of 10% for this brief intervention. We  
propose to recruit 40 older adults of which 36 (90%) will complete the study.  
Compensation and Retention. Participants will be financially compensated with $300 in total for 
completing the study protocol (approximately for 15 hours of time); participants who only partially 
complete the protocol will be compensated based on prorated hours. To maximize participant retention 
we will maintain contact with participants over time via frequent assessment intervals (e.g., requiring a 
functioning phone number and email address to contact participants by phone or email as needed, and 
obtaining the name, address, and phone number of at least 2 friends or classmates who can provide 
contact information for the participants, should we be unable to contact them during the study; emails 
and reminder phone calls prior to all study visits; offer flexible scheduling options for assessment (including 
weekends); provide fair compensation to participants; and maintain positive relations with participants. 
These procedures were used to maintain adequate participant retention in our prior NIH studies. 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
Experimental Manipulation – IBMT (Arm 1): IBMT emphasizes the cooperation 
between body and mind in facilitating and achieving a meditative state ecologically. 1-7,18-22 Each IBMT 
session is facilitated by an experienced and certified coach who has demonstrated the ability to attain the 
appropriate state of body and mind, and to lead the group to achieve a similar state. The coach creates a 
harmonious and relaxed atmosphere, observes facial and body cues to identify those who are struggling 
with the method, and gives proper feedback for effective practice. IBMT coach helps subjects attain 
desired state by first providing a brief period to induce a cognitive or emotional state that will facilitate 

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the training. Then, coach helps subjects find an appropriate and balanced body posture and follow 
instructions to achieve deeper levels of relaxed body (physiology of relaxation) and experience a restful 
feeling and mental quiet (psychology of relaxation) mindfully. 
When the mind wanders, the coach helps subjects accept and be open to experiences without judgment, 
and further guides subjects to use a favorite mental image as a tool to return to the present moment 
gently. At last, the coach facilitates a brief group discussion to ensure subjects having positive experiences 
consistent with the intent of IBMT. The method stresses no effort to control thoughts, but instead 
emphasizes a state of restful alertness that allows a high degree of awareness of the body, mind, and 
environment. 1-7,18-22 
Control Intervention – Health Education (Arm 2): For HE, each session includes pre-, post- and practice 
sessions, similar to IBMT procedure and is facilitated by a trained coach. However, HE involves teaching 
participants different health promotion skills, behavior, attitude and strategies, which are guided by the 
certified coach. Participants have an active group experience that is not mindfulness-related. Therefore, 
HE induces a comparable but different experience and could serve as an ideal active control. Moreover, 
other groups have been using HE as active control in RCTs involving mindfulness intervention as an active 
control condition. 2,7,64,65  
6.1.2 ADMINISTRATION AND/OR DOSING 
Both arms of interventions will be administered as a group by trained interventionists. Both interventions 
will have 10 consecutive group sessions, and the completion of all 10 sessions is considered to be having a 
“full-dose” intervention. Participants in the same arm/group will interact with a shared interventionist.  
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
Explicit coach selection criteria and on-going monitoring and supervision of treatment delivery and fidelity 
will ensure that the interventions are of the highest quality, follow the protocols precisely, and prevent 
coach drift and contamination. For IBMT and HE, the coach must have a minimum of a master’s degree in 
psychology, social work, or a related field and experience running group therapy. The coach will need to 
meet additional criteria: have completed the trainer course, had a daily practice of mindfulness, and 
attended a silent meditation retreat. To monitor coach’s adherence and competence, all sessions will be 
recorded and a random sample of 10% will be rated by the investigators using the modified Adherence 
Scale to ensure the interventionist has adequate competence and adherence to the protocols, and to 
prevent drift. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
To minimize potential biases, participants are randomized based on automatic covariate conducted by Co-
I using an adaptive algorithm. Participants are blinded to the intervention. Specifically, they were told that 
they will be engaged in body-mind intervention, without knowing whether or not the intervention they 
received is the experimental manipulation or control intervention. See methods of analysis in Section 9, 
Statistical Considerations for details on randomization. Additionally, research staff who assesses 
participants are also blinded of the participants’ intervention condition. Randomization code is maintained 
by different research staff. A planned breaking of randomization code and blinding would occur for any 

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participants who reported serious adverse events. The PI and Co-I will identify which group the participant 
is in, without the need for research staff to be involved in knowing the participant’s intervention group.  
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
Participants’ adherence with study procedures will be tracked by taking their attendance at intervention 
visits. Moreover, in each session, we use participant self-report and coach observation to calculate study 
intervention adherence by the participant based on their engagement and quality of practice.  
6.5 
CONCOMITANT THERAPY 
N/A 
6.5.1 RESCUE THERAPY 
N/A 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
If a clinically significant finding is identified (including, but not limited to changes from baseline) after 
enrollment, the investigator or qualified designee will determine if any change in participant management 
is needed. Any new clinically relevant finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
The reason(s) for discontinuing the participant from the intervention, and methods for 
determining the need to discontinue 
• 
If the participant is due to complete assessments within 1 weeks of being discontinued from the 
study intervention, those assessments will be administered at the time of discontinuation; if the next 
scheduled assessments are more than 1 week from the discontinuation date, the next scheduled 
assessment will not be administered. Thereafter, the participant will be not included in all future 
scheduled assessments, as they did not participate in the intervention. 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance, unless varying compliance is an aspect of the study 
objectives  
• 
Lost-to-follow up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up  
study data would not be in the best interest of the participant or might require an additional 
treatment that would confound the interpretation of the study 

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• 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
The reason for participant discontinuation or withdrawal from the study will be recorded. Subjects who 
sign the informed consent form and are randomized but do not receive the study intervention may be 
replaced. Subjects who sign the informed consent form, and are randomized and receive the study 
intervention, and subsequently withdraw, or are discontinued from the study, will not be replaced. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for 1 scheduled visit and study 
staff are unable to contact the participant after at least 3 attempts.  
 
The following actions must be taken if a participant fails to return for a required study visit: 
 
• 
The site will attempt to contact the participant, reschedule the missed visit within 1 week, counsel 
the participant on the importance of maintaining the assigned visit schedule and ascertain if the 
participant wishes to and/or should continue in the study 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods).  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
The study involves assessing participants at baseline, post-intervention, and 3-month follow-up. The 
participant will be screened for eligibility after consenting. They will fill out demographic questionnaires 
and MRI screening form to determine their eligibility. Next, they will undergo behavioral, cognitive, and 
brain assessments by trained research staff and/or MRI technician. All non-brain assessments will be 
conducted at PI’s lab for all participants to decrease variability. All brain assessments will be conducted at 
Barrow Neurological Institute for all participants to decrease variability.    
 
Below is a list and description of the assessments: 
• 
Performance-based assessments  
Cognitive assessments – N-Back working memory is a memory performance test 
• 
Administration of questionnaires, interviews 
Behavioral assessments – Emotional Regulation Questionnaire assesses emotion regulation, Five 
Facet Mindfulness Questionnaire assesses mindfulness, Subjective Cognitive Decline questionnaire 
assesses subjective report of cognitive decline  
• 
Imaging assessments  
MRI Scan – provides images of brain structure and function 
8.2 
SAFETY ASSESSMENTS 

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N/A 
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
 
This protocol uses the definition of adverse event from 21 CFR 312.32 (a): any untoward medical 
occurrence associated with the use of an intervention in humans, whether or not considered intervention-
related. 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
This protocol uses the definition of serious adverse event includes: (a) Death; (b) Hospitalization (initial or 
prolonged); (c) Life-threatening condition; (d) Disability or Permanent Damage; (e) Other Serious 
(Important Medical Events). 
 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines will 
be used to describe severity.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
All adverse events (AEs) will have their relationship to study procedures, including the intervention, 
assessed by an appropriately-trained clinician based on temporal relationship and his/her clinical 
judgment. The degree of certainty about causality will be graded using the categories below.  
 
• 
Related – The AE is known to occur with the study procedures, there is a reasonable possibility 
that the study procedures caused the AE, or there is a temporal relationship between the study 

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procedures and the event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study procedures and the AE. 
• 
Not Related – There is not a reasonable possibility that the study procedures caused the event, 
there is no temporal relationship between the study procedures and event onset, or an alternate 
etiology has been established. 
 
8.3.3.3 EXPECTEDNESS  
 
A clinician with appropriate expertise in medical care will be responsible for determining whether an 
adverse event (AE) is expected or unexpected. An AE will be considered unexpected if the nature, severity, 
or frequency of the event is not consistent with the risk information previously described for the study 
procedures. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs, not otherwise precluded per the protocol, will be captured on the appropriate case report form 
(CRF). Information to be collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study procedures (assessed only by those with the training and authority to make 
a diagnosis), and time of resolution/stabilization of the event. All AEs occurring while on study will be 
documented appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
 
PI will record events with start dates occurring any time after informed consent is obtained until 7 (for 
non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  At each study visit, the 
investigator will inquire about the occurrence of AE/SAEs since the last visit.  Events will be followed for 
outcome information until resolution or stabilization. 
8.3.5 ADVERSE EVENT REPORTING  
In consultation with the PI, a trained member of the study team will be responsible for conducting an 
evaluation of an adverse event and shall report the results of such evaluation to the NIH and the reviewing 
Institutional Review Board (IRB) as soon as possible, but in no event later than 24 hours after the 
investigator first learns of the event. 

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8.3.6 SERIOUS ADVERSE EVENT REPORTING  
 
In consultation with the PI, a trained member of the study team will be responsible for conducting an 
evaluation of a serious adverse event and shall report the results of such evaluation to the NIH and the 
reviewing Institutional Review Board (IRB) as soon as possible, but in no event later than 24 hours after 
the investigator first learns of the event. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
The PI will be responsible for reporting AEs or SAEs related to the study to participants as soon as possible, 
but in no event later than 24 hours after the investigator first learns of the event. 
For incidental findings from MRI brain scan, the MRI facility will inform the PI if there is incidental finding 
and the PI will report the finding to participants as soon as possible, but in no event later than 24 hours 
after the investigator first learns of the event. 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
8.3.9 REPORTING OF PREGNANCY  
N/A  
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human Research 
Protections (OHRP).  OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 

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8.4.2  UNANTICIPATED PROBLEMS REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will include 
the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DCC/study 
sponsor/funding agency within 10 business days of the investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor/funding agency within 10 
business days of the investigator becoming aware of the problem  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 10 business days of the IRB’s receipt of the report of 
the problem from the investigator. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
The PI will be responsible for reporting UPs related to the study to participants as soon as possible, but in 
no event later than 10 working days after the investigator first learns of the UP. 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
 
• 
Primary Endpoint(s):  
We hypothesize that, compared to participants who receive a control intervention, participants who 
receive IBMT for improving behavior and cognition will have improved working memory, emotion 
regulation, and reduced subjective report of cognitive decline after completing the intervention at 
post-assessment, and will continue to show improvement 3 months after the intervention. 
Alternatively, our null hypothesis is that there will be no difference in the effects of IBMT for improving 
behavior and cognition and those of control intervention at post-assessment or after 3 months of 
intervention. 
 
• 
Secondary Endpoint(s): 

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We hypothesize that, compared to participants who receive a RT control intervention, participants 
who receive IBMT for improving brain function and structure will have improved white matter, grey 
matter, and functional connectivity in AD-signature regions after completing the intervention at post-
assessment, and will continue to show improvement 3 months after the intervention. Alternatively, 
our null hypothesis is that there will be no difference in the effects of IBMT for improving brain 
function and structure and those of RT at post-assessment or after 3 months of intervention. 
9.2 
SAMPLE SIZE DETERMINATION 
Our series of RCTs suggest that IBMT showed significant effects in relatively small sample size 1-44 . For 
example, a recent RCT in healthy older adults showed significant effects on quality of life (N=25) and in 
resting state functional connectivity and structural changes in the ACC/mPFC-Striatum networks following 
IBMT (N=13) 4; In adults, we detected significant fMRI signal changes in the ACC/mPFC (Cohen’s d= .90) 
after 10-session IBMT 9,11 . We used GPower 3.1 software to determine the smallest detectable effect for 
a treatment X time interaction term given various sample sizes and a power of 0.80, assuming varying 
correlations between repeated measures, which ranged from .30 -.60 on behavioral and .50 -.80 on fMRI 
measures in our prior studies 1-44 . Considering these factors, our target N of 40 after attrition will allow 
us to detect small-medium-sized effects on continuous outcomes. The N of 40 will provide a reasonable 
sample to determine the effect size of IBMT without utilizing an unreasonable amount of resources in this 
pilot. Specifically, 40 subjects will give us adequate statistical power (80%) to detect a medium effect size 
[f= 0.3 for ANOVA and h=0.6 for proportion difference] with alpha=0.05 for analysis proposed. This effect 
size is conservatively estimated based on our previous studies 5,8-12. The Chi-square test would be less 
statistically powerful; however, as the nature of this project is exploratory, we are interested in 
determining the potential effect size of intervention and in developing our intervention protocol in older 
adults before testing it in a larger sample size. 
Given the 1-year project with pre, post-intervention and follow-up and power considerations, the N of 40 
we choose is also in line with our intervention cycles and capacities. 
9.3 
POPULATIONS FOR ANALYSES 
The analysis population will be Modified Intention-to-Treat Analysis Population. Specifically, these 
participants are those who completed the full-dose of the intervention (10 sessions) and have 
complete and usable data for the primary endpoints.  
9.4 
STATISTICAL ANALYSIS PLAN 
9.4.1 GENERAL APPROACH 
Behavioral and brain data analysis will undergo separate analyzing streams to test intervention effects 
and underlying mechanisms at different time points. Given the scope of this 1-year pilot project, the 
logical first step at this early stage of research is to examine the potential intervention effects and 
mechanisms in small sample size, then move to the full scale RCTs for replication. To address our study 
Aims, repeated-measures ANOVA will be used. By utilizing all assessment points, this approach allows 
for well-powered tests to detect significant differences in changes across the experimental conditions, 
even when assuming smaller magnitude effect sizes. Effect size measures (from the repeated-
measures ANOVA, Cohen’s d highlighting mean differences between treatment and control groups 
across assessments) will also be calculated to describe the intervention’s effect on study outcomes. 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 

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The primary endpoints are behavioral and cognitive assessments and are all repeated measures assessed 
at baseline, post-intervention, and 3-month follow-up. For cognitive assessment of N-Back working 
memory, percentage of correct trials will be calculated for each trial for all endpoints. For behavioral 
assessment of emotion regulation, mindfulness, and SCD, these self-report questionnaires will be 
calculated based on established scoring guides by summing all items within a given questionnaire for all 
endpoints. Next, the effects of intervention (IBMT vs. HE) on each of these primary endpoints will be 
examined using repeated-measures ANOVA with time x group interaction effect. Variance and covariance 
across repeated measures will be calculated as part of the ANOVA. Age and sex will be included as 
covariates to control for potential confounding effects of age and sex on behavioral and cognitive 
assessments. Results will be presented as F values for the interaction effect, along with p values to indicate 
statistical significance. Normality and homogeneity of variance assumptions will be checked using SPSS 
built-in tools for ANOVA. Because there are 4 primary endpoints, multiple comparison corrections will be 
conducted using FDR correction. Missing data will be handled with case-wise deletion. 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
The secondary endpoints are brain assessments and are all repeated measures assessed at baseline, post-
intervention, and 3-month follow-up. For brain assessment of white matter, white matter integrity metrics 
will be calculated for all endpoints based on standardized processing pipelines of diffusion-based white 
matter data using FSL (http://www.fmrib.ox.ac.uk/fsl). For brain assessment of grey matter, cortical 
thickness and volume metrics will be calculated for all endpoints based on standardized processing 
pipelines of structural MRI data using SPM12 (http://www.fil.ion.ucl.ac.uk/spm). For brain assessment of 
functional connectivity, pair-wise correlations of fMRI timeseries will be calculated for regions of interest 
and for all endpoints based on standardized processing pipelines of fMRI data using REST software 
(www.restfmri.net). After these data preprocessing and calculation, numerical values will be generated 
for all secondary endpoints (white matter, grey matter, and functional connectivity). Next, the effects of 
intervention (IBMT vs. HE) on each of these secondary endpoints will be examined using repeated-
measures ANOVA with time x group interaction effect. Variance and covariance across repeated measures 
will be calculated as part of the ANOVA. Age and sex will be included as covariates to control for potential 
confounding effects of age and sex on brain function and structure. Results will be presented as F values 
for the interaction effect, along with p values to indicate statistical significance. Normality and 
homogeneity of variance assumptions will be checked using SPSS built-in tools for ANOVA. Because there 
are 3 secondary endpoints, multiple comparison corrections will be conducted using FDR correction. 
Missing data will be handled with case-wise deletion. 
9.4.4 SAFETY ANALYSES 
N/A 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Intervention groups will be compared on baseline characteristics including demographics, behavioral 
assessments of emotion regulation, mindfulness, and subjective cognitive decline, as well as cognitive 
assessment of N-Back working memory performance using independent samples t-tests.  

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9.4.6 PLANNED INTERIM ANALYSES  
 N/A 
 
9.4.7 SUB-GROUP ANALYSES 
Sub-group analyses will not be conducted for primary and secondary outcomes for this pilot study, as the 
sample size of sub-groups (N<10) based on age, sex, race/ethnicity or other demographic characteristic(s) 
will not be sufficient to conduct meaningful group analyses. 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be tabulated as the goal of the study is to examine group effects. 
 
9.4.9 EXPLORATORY ANALYSES 
N/A 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and risks will be given to the 
participant and written documentation of informed consent will be completed prior to starting the study 
intervention.  The following consent materials are submitted with this protocol: Consent Form, see Section 
12 Attachment. 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent will be administered by a member of the study team to the participant. The team 
member will give the participant a brief overview of the consent form and summarize relevant information 
from each section of the consent form. Participants will then be given time to read the consent form on 
their own. The study population involves English speaking cognitively normal adults, so no special 
procedures are needed to obtaining the consent. Participants will be asked if they understand and 
comprehend the consent form and if they have any questions. These procedures serve as means for 
determining competency and assessing comprehension/understanding of the participants. Any questions 

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the participants may have will be answered by the team member. Finally, participants are asked to 
indicate if they would like to enroll in the study or not by signing or not signing the consent form. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, funding agency, and regulatory authorities. 
If the study is prematurely terminated or suspended, the Principal Investigator (PI) will promptly inform 
study participants, the Institutional Review Board (IRB), and sponsor/funding agency and will provide the 
reason(s) for the termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance of study staff to the protocol (ie, significant protocol violations) 
• 
Pandemic, such as COVID-19 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the funding agency, sponsor, IRB, Food and Drug Administration (FDA), or other relevant 
regulatory or oversight bodies (OHRP, DSMB). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, 
the safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is 
extended to the data being collected as part of this study. Data that could be used to identify a specific 
study participant will be held in strict confidence within the research team. No personally-identifiable 
information from the study will be released to any unauthorized third party without prior written approval 
of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, representatives of 
the Institutional Review Board (IRB), regulatory agencies, may inspect all documents and records required 
to be maintained by the investigator. The study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at the study site for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure location for as long a 
period as dictated by the reviewing IRB, Institutional policies, or sponsor/funding agency requirements. 
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made available 
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share data will include proper plans and safeguards for the protection of privacy, confidentiality, and 
security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be 
traceable to a specific study participant). Plans for archiving and long-term preservation of the data will 
be implemented, as appropriate.  
 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has 
issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical 
or other human subjects research funded wholly or in part by the federal government.  Recipients of NIH 
funding for human subjects research are required to protect identifiable research information from forced 
disclosure per the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth 
in 45 CFR Part 75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered 
by this Policy are required to establish and maintain effective internal controls (e.g., policies and 
procedures) that provide reasonable assurance that the award is managed in compliance with Federal 
statutes, regulations, and the terms and conditions of award. It is the NIH policy that investigators and 
others who have access to research records will not disclose identifying information except when the 
participant consents or in certain instances when federal, state, or local law or regulation requires 
disclosure. NIH expects investigators to inform research participants of the protections and the limits to 
protections provided by a Certificate issued by this Policy. 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Data collected for this study will be analyzed and stored at the study site. After the study is completed, 
the de-identified, archived data will be transmitted to and stored at the study site’s secured data storage 
space. The use of the de-identified data by other researchers including those outside of the study will be 
granted per reasonable requests.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 
Independent Data Safety 
Monitor 
Yi-Yuan Tang, Ph.D., Professor 
Elliot Stein, Ph.D., Investigator 
Arizona State University  
National Institute on Drug Abuse 
425 N 5th St, Phoenix, AZ 85004 
251 Bayview Boulevard Suite 
200, Baltimore, MD 21224 
4807903577 
4437402650 
yiyuan@asu.edu 
stein@mail.nih.gov 
 
10.1.6 SAFETY OVERSIGHT 
 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) composed of 
individuals with the appropriate expertise, including clinical trials and intervention. Members of the DSMB 
will be independent from the study conduct and free of conflict of interest. The DSMB will meet at least 
semiannually to assess safety and efficacy data from each arm of the study. The DSMB will operate under 

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the rules of an approved charter that will be written and reviewed at the organizational meeting of the 
DSMB. At this time, each data element that the DSMB needs to assess will be clearly defined. The DSMB 
will provide its input to NCCIH via annual report. 
 
10.1.7 CLINICAL MONITORING 
Clinical site monitoring will be conducted to ensure that the rights and well-being of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), with International 
Council on Harmonisation Good Clinical Practice (ICH GCP), and with applicable regulatory 
requirement(s). Monitoring activities will be conducted by the study site itself, so please see Section 
10.1.8, Quality Assurance and Quality Control. 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
The study site will perform internal quality management of study conduct, data collection, documentation 
and completion. Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- Study staff will review both the documentation of the consenting process as well as 
a percentage of the completed consent documents.  This review will evaluate compliance with GCP, 
accuracy, and completeness.  Feedback will be provided to the study team to ensure proper consenting 
procedures are followed.  
 
Source documents and the electronic data --- Data will be initially captured on source documents (see 
Section 10.1.9, Data Handling and Record Keeping) and will ultimately be entered into the study 
database.  To ensure accuracy site staff will compare a representative sample of source data against the 
database, targeting key data points in that review. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will 
implement corrective actions when the quantity or nature of deviations are deemed to be at a level of 
concern. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/funding agency, and inspection by local and regulatory authorities. 
 

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10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Data collection will be the responsibility of study team at the site under the supervision of the site 
investigator. The investigator will be responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 
All source documents will be completed in a neat, legible manner to ensure accurate interpretation of 
data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant consented/enrolled in the study.  Data recorded in the electronic case 
report form (eCRF) derived from source documents will be consistent with the data recorded on the 
source documents.  
 
Clinical data (including adverse events (AEs) and SAEs will be entered into RedCap provided by the study 
site. The data system includes password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be entered 
directly from the source documents. 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 2 years after the study completion date. These 
documents should be retained for a longer period, however, if required by local regulations. No records 
will be destroyed without the written consent of the sponsor/funding agency, if applicable. It is the 
responsibility of the sponsor/funding agency to inform the investigator when these documents no longer 
need to be retained. 
 
10.1.10 
PROTOCOL DEVIATIONS   
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol, 
International Council on Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) 
requirements. The noncompliance may be either on the part of the participant, the investigator, or the 
study site staff. As a result of deviations, corrective actions will be developed by the site and implemented 
promptly.  
 
These practices are consistent with ICH GCP:  
• 
Section 4.5 Compliance with Protocol, subsections 4.5.1, 4.5.2, and 4.5.3  
• 
Section 5.1 Quality Assurance and Quality Control, subsection 5.1.1  
• 
Section 5.20 Noncompliance, subsections 5.20.1, and 5.20.2.  

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It will be the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10 working days of 
the scheduled protocol-required activity. All deviations will be addressed in study source documents, 
reported to NCCIH Program Official and NCCIH. Protocol deviations will be sent to the reviewing 
Institutional Review Board (IRB) per their policies. The site investigator will be responsible for knowing 
and adhering to the reviewing IRB requirements. 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed 
journals.  Data from this study may be requested from other researchers 10 years after the completion of 
the primary endpoint by contacting PI Yi-Yuan Tang.  Considerations for ensuring confidentiality of these 
shared data are described in Section 10.1.3. 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the design and conduct of this trial. The study leadership in 
conjunction with the NCCIH has established policies and procedures for all study group members to 
disclose all conflicts of interest and will establish a mechanism for the management of all reported 
dualities of interest. 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 

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AE 
Adverse Event 
ANOVA 
Analysis of Variance 
CFR 
Code of Federal Regulations 
COC 
Certificate of Confidentiality 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
fMRI 
Functional Magnetic Resonance Imaging 
HE 
Health Education 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
HIPAA 
Health Insurance Portability and Accountability Act  
IBMT 
Integrative Body Mind Training 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
ITT 
Intention-To-Treat 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Activities 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
1.0 
02/10/2022 
Initial protocol 
Initial protocol 
1.1 
06/22/2022 
Added RAs to the study team, COVID 
screening 
Modification 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
1) Tang, Y. Y., Ma, Y., Wang, J., Fan, Y., Feng, S., Lu, Q., Yu, Q., Sui, D., Rothbart, M. K., Fan, M., & 
Posner, M. I. (2007). Short-term meditation training improves attention and self-regulation. 
Proceedings of the National Academy of Sciences, 104(43), 17152-17156. 
2) Tang, Y. Y. (2017). The Neuroscience of Mindfulness Meditation: How the Body and Mind 
Work Together to Change Our Behavior? Springer Nature 
3) Tang, Y. Y., Posner, M. I., & Rothbart, M. K. (2014). Meditation improves self‐regulation 
over the life span. Annals of the New York Academy of Sciences, 1307(1), 104-111. 
4) Tang, Y. Y., Fan Y, Lu Q, Tan LH, Tang R, Kaplan R, Pinho, M.C., Thomas, B.P., Che K, Friston KJ, 
Reiman EM. (2020). Comparison of long-term physical exercise and meditation practice in an 
aging population. Frontiers in Psychology, in press 
5) Tang, Y. Y., Ma, Y., Fan, Y., Feng, H., Wang, J., Feng, S., Lu, Q., Hu, B., Lin, Y., Li, J., Zhang, Y., 
Wang, Y., Zhou, L., & Fan, M. (2009). Central and autonomic nervous system interaction is 
altered by short-term meditation. Proceedings of the National Academy of Sciences, 106(22), 
8865-8870. 
6) Tang, Y. Y., Tang R, Gross JJ. (2019). Promoting emotional well-being through an evidence-
based mindfulness training program. Frontiers in Human Neuroscience. 13:237 
7) Tang, Y. Y., Holzel, B.K., Posner, M.I. (2015). The neuroscience of mindfulness meditation. 
Nature Reviews Neuroscience, 16(4), 213-225  
8) Tang, Y. Y., Lu, Q., Geng, X., Stein, E. A., Yang, Y., & Posner, M. I. (2010). Short-term 
meditation induces white matter changes in the anterior cingulate. Proceedings of the National 
Academy of Sciences, 107(35), 15649-15652. 
9) Tang, Y. Y., Lu, Q., Fan, M., Yang, Y., & Posner, M. I. (2012). Mechanisms of white matter 
changes induced by meditation. Proceedings of the National Academy of Sciences, 109(26), 
10570-10574. 
10) Tang, Y. Y., Tang Y, Tang R, Lewis-Peacock J. (2017). Brief mental training reorganizes large-
scale networks. Frontiers in Systems Neuroscience, 11:6 
11) Tang, Y. Y., Tang, R., & Posner, M. I. (2013). Brief meditation training induces smoking 
reduction. Proceedings of the National Academy of Sciences, 110(34), 13971-13975. 
12) Tang, Y. Y., Lu Q, Feng H, Tang R, Posner MI. (2015). Short-term meditation increases blood 
flow in anterior cingulate cortex and insula. Frontiers in Psychology, 6:212. 
13) Tang, Y. Y., Yang, L., Leve, L. D., & Harold, G. T. (2012). Improving executive function and its 
neurobiological mechanisms through a mindfulness‐based intervention: Advances within the 
field of developmental neuroscience. Child development perspectives, 6(4), 361-366. 
14) Tang, Y. Y., Holzel BK, Posner MI. (2016). Traits and states in mindfulness meditation. 
Nature Reviews Neuroscience, 17(1):59 
15) Wei GX, Si GY, Tang, Y. Y. (2017). Brain-mind-body Practice and Health. Frontiers in 
Psychology, 8:1886 
16) Tang, Y. Y., Jiang C, Tang R. (2017). How mind-body practice works - integration or 
separation? Frontiers in Psychology, 8:6 
17) Tang, Y. Y., Bruya B. (2017). Mechanisms of mind-body interaction and optimal 
performance. Frontiers in Psychology, 8:1 

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18) Tang, Y. Y. (2011). Mechanism of integrative body-mind training. Neuroscience Bulletin, 
27(6), 383-388. 
19) Tang, Y. Y. (2009). Exploring the brain, optimizing the life. Beijing: Science Press. 
20) Tang, Y. Y. (2017). Brain-Based Learning and Education: Principle and Practice. Academic 
Press, Elsevier 
21) Tang, Y. Y., Tang R. (2020). The Neuroscience of Meditation: Understanding Individual 
Differences. Academic Press, Elsevier 
22) Tang, Y. Y., & Posner, M. I. (2009). Attention training and attention state training. Trends in 
cognitive sciences, 13(5), 222-227. 
23) Fan, Y., Tang, Y. Y., Tang, R., Posner, M.I. (2014). Short term integrative meditation improves 
resting alpha activity and Stroop performance. Applied Psychophysiology and Biofeedback, 
39(3-4), 213-7. 
24) Fan, Y., Tang, Y. Y., Tang, R., Posner, M.I. (2015). Time course of conflict processing 
modulated by brief meditation training. Frontiers in Psychology, 6: 911 
25) Ding, X., Tang, Y. Y., Cao, C., Deng, Y., Wang, Y., Xin, X., Posner, M.I. (2015). Short-term 
meditation modulates brain activity of insight evoked with solution cue. Social Cognitive and 
Affective Neuroscience, 10(1), 43-9. 
26) Ding, X., Tang, Y. Y., Tang, R., Posner, M.I. (2014). Improving creativity performance by 
short-term meditation. Behavioral and Brain Functions, 10:9 
27) Ding, X., Tang, Y. Y., Deng, Y., Tang, R., Posner, M.I. (2015). Mood and personality predict 
improvement in creativity due to meditation training. Learning and Individual Differences, 37, 
217-221 
28) Xin X, Deng Y, Ding X, Tang, Y. Y. (2014). Short-term meditation improves working memory 
performance through changing frontal-parietal network efficiency. Psychophysiology, 51 (S1), 
152 
29) Tang, Y. Y., Tang R, Jiang C, Posner MI. (2014). Short-term meditation intervention improves 
self-regulation and academic performance. J Child Adolesc Behav. 2:4  
30) Fan, Y., Tang, Y. Y., & Posner, M. I. (2014). Cortisol level modulated by integrative 
meditation in a dose‐dependent fashion. Stress and Health, 30(1), 65-70. 
31) Fan, Y., Tang, Y. Y., Ma, Y., Posner, M.I. (2010). Mucosal immunity modulated by integrative 
meditation in a dose dependent fashion. J Altern Complement Med. 16(2):151-5 
32) Tang, Y. Y., Posner, M. I., Rothbart, M. K., & Volkow, N. D. (2015). Circuitry of self-control 
and its role in reducing addiction. Trends in cognitive sciences, 19(8), 439-444.  
33) Xue S, Tang, Y. Y., Tang R, Posner MI. (2014). Short-term meditation induces changes in 
brain resting EEG theta networks. Brain and Cognition, 87, 1-6.  
34) Xue S, Deng Y, Tang, Y. Y. (2012). Coherent spontaneous resting EEG of frontal regions in 
human brain. BMC Neuroscience, 13(S1): 25 
35) Xue S, Tang, Y. Y., Posner MI. (2011). Short-term meditation increases network efficiency of 
the anterior cingulate cortex. NeuroReport, 22(12): 570-4 
36) Tang, Y. Y., Rothbart, M. K., & Posner, M. I. (2012). Neural correlates of establishing, 
maintaining, and switching brain states. Trends in cognitive sciences, 16(6), 330-337. 
37) Tang, Y. Y., Posner MI. (2014). Training brain networks and states. Trends in Cognitive 
Sciences, 18(7):345-50  

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38) Tang, Y. Y., Tang, R., & Posner, M. I. (2016). Mindfulness meditation improves emotion 
regulation and reduces drug abuse. Drug and alcohol dependence, 163, S13-S18. 
39) Tang, Y. Y., Leve LD. (2016). A translational neuroscience perspective on mindfulness 
meditation as a prevention strategy. Translational Behavioral Medicine, 6(1):63-72 
40) Tang, Y. Y., Tang R. (2015). Rethinking the future directions of mindfulness field. 
Psychological Inquiry, 26(4): 368-372 
41) Tang, Y. Y., & Posner, M. I. (2012). Tools of the trade: theory and method in mindfulness 
neuroscience. Social cognitive and affective neuroscience, 8(1), 118-120. 
42) Posner MI, Rothbart MK, Tang, Y. Y. (2015). Enhancing attention through training. Current 
Opinion in Behavioral Sciences, 4:1-5 
43) Posner MI, Tang, Y. Y., (2014). Lynch G. Mechanisms of white matter change induced by 
meditation training. Frontiers in Psychology, 5:1220 
44) Tang, Y. Y., Tang R, Rothbart MK, Posner MI. (2019). Frontal theta activity and white matter 
plasticity following mindfulness meditation. Current Opinions in Psychology, 28, 294-297 
45) Brewer JA, Worhunsky PD, Gray JR, Tang, Y. Y., Weber J, Kober H. (2011). Meditation 
experience is associated with differences in default mode network activity and connectivity. 
Proceedings of the National Academy of Sciences, USA, 108(50): 20254-9. 
46) Jessen F, et al. (2014). A conceptual framework for research on subjective cognitive decline 
in preclinical Alzheimer’s disease. Alzheimers Dement 10, 844–52. 
47) Jessen F, et al. (2020). The characterisation of subjective cognitive decline. Lancet Neurol 
19(3), 271-278. 
48) Mitchell A, Beaumont H, Ferguson D, Yadegarfar M, Stubbs B. (2014). Risk of dementia and 
mild cognitive impairment in older people with subjective memory complaints: meta-analysis. 
Acta Psychiatr Scand 130: 439–51. 
49) Slot, RER, et al. (2019). Subjective cognitive decline and rates of incident Alzheimer’s 
disease and non-Alzheimer’s disease dementia. Alzheimers Dement 15: 456–76. 
50) Bhome R, Berry AJ, Huntley JD, Howard RJ. (2018). Interventions for subjective cognitive 
decline: systematic review and meta-analysis. BMJ Open 8:e021610. 
51) Larouche, E., Hudon, C., Goulet, S. (2015). Potential benefits of mindfulness-based 
interventions in mild cognitive impairment and Alzheimer’s disease: An interdisciplinary 
perspective. Behavioural Brain Research, 276, 199-212. 
52) Tao J, Liu J, Egorova N, Chen X, Sun S, Xue X, Huang J, Zheng G, Wang Q, Chen L, Kong J. 
(2016). Increased hippocampus-medial prefrontal cortex resting-state functional connectivity 
and memory function after Tai Chi Chuan practice in elder adults. Front Aging Neurosci. 8:25.  
53) Smart CM, Segalowitz SJ, Mulligan BP, Koudys J, Gawryluk JR. (2016). Mindfulness training 
for older adults with subjective cognitive decline: results from a pilot randomized controlled 
trial. J Alzheimers Dis. 52(2), 757-74.  
54) Smart CM, et al. (2017). Non-Pharmacologic interventions for older adults with subjective 
cognitive decline: systematic review, meta-analysis, and preliminary recommendations. 
Neuropsychol Rev. 27(3):245-257. 
55) Tao J, et al. (2017) Tai Chi Chuan and Baduanjin increase grey matter volume in older adults: 
a brain imaging study. J Alzheimers Dis. 60(2), 389-400. 

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56) Lim KH, Pysklywec A, Plante M, Demers L. (2019). The effectiveness of Tai Chi for short-term 
cognitive function improvement in the early stages of dementia in the elderly: a systematic 
literature review. Clin Interv Aging. 14, 827-839.  
57) Berk L, van Boxtel M, van Os J. (2017). Can mindfulness-based interventions influence 
cognitive functioning in older adults? A review and considerations for future research. Aging 
Ment Health. 21(11), 1113-1120. 
58) Gard T, Hölzel BK, Lazar SW. (2014). The potential effects of meditation on age-related 
cognitive decline: a systematic review. Ann N Y Acad Sci. 1307, 89-103. 
59) Chiesa, A., et al. (2011). Does mindfulness training improve cognitive abilities? a systematic 
review of neuropsychological findings. Clin Psychol Rev 31 (3), 449-64. 
60) Marchant NL, et al. (2018). The SCD-Well randomized controlled trial: Effects of a 
mindfulness-based intervention versus health education on mental health in patients with 
subjective cognitive decline (SCD). Alzheimers Dement (N Y). 4, 737–745. 
61) Gard T, Hölzel BK, Lazar SW. (2014). The potential effects of meditation on age-related 
cognitive decline: a systematic review. Ann N Y Acad Sci. 1307, 89-103. 
62) Chiesa, A., et al. (2011). Does mindfulness training improve cognitive abilities? a systematic 
review of neuropsychological findings. Clin Psychol Rev 31 (3), 449-64. 
63) Marchant NL, et al. (2018). The SCD-Well randomized controlled trial: Effects of a 
mindfulness-based intervention versus health education on mental health in patients with 
subjective cognitive decline (SCD). Alzheimers Dement (N Y). 4, 737–745. 
64) Rosenkranz MA, Davidson RJ, Maccoon DG, Sheridan JF, Kalin NH, Lutz A. (2013). A 
comparison of mindfulness-based stress reduction and an active control in modulation of 
neurogenic inflammation. Brain Behav Immun. 27, 174-84. 
65) MacCoon DG, MacLean KA, Davidson RJ, Saron CD, Lutz A. (2014). No sustained attention 
differences in a longitudinal randomized trial comparing mindfulness based stress reduction 
versus active control. PLoS One. 9, e97551. 
66) Benedictus MR, et al. (2015). White matter hyperintensities relate to clinical progression in 
subjective cognitive decline. Stroke. 46, 2661-4.  
67) van Rooden S, et al. (2018). Subjective cognitive decline is associated with greater white 
matter hyperintensity volume. J Alzheimers Dis. 66, 1283-1294. 
68) Pegueroles J et al & Alzheimer's Disease Neuroimaging Initiative. (2017). Longitudinal brain 
structural changes in preclinical Alzheimer's disease. Alzheimer's & Dementia, 13(5), 499-509.   
69) Veitch DP, et al. Alzheimer's Disease Neuroimaging Initiative. (2019). Understanding disease 
progression and improving Alzheimer's disease clinical trials: Recent highlights from the 
Alzheimer's Disease Neuroimaging Initiative. Alzheimer's & Dementia, 15, 106-152. 
70) Farokhian F, et al. (2017). Age-related gray and white matter changes in normal adult 
brains. Aging Dis. 8, 899–909.  
71) Fjell AM, et al. (2006). Selective increase of cortical thickness in high-performing elderly--
structural indices of optimal cognitive aging. Neuroimage. 29(3), 984-94. 
72) Reiman EM, et al. (2001). Declining brain activity in cognitively normal apolipoprotein E 
epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently 
test treatments to prevent Alzheimer's disease. Proc Natl Acad Sci U S A. 98(6), 3334-9. 

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73) Uschner, D., Schindler, D., Hilgers, R. D., & Heussen, N. (2016). randomizeR: an R package 
for the assessment and implementation of randomization in clinical trials. Journal of Statistical 
Software.  
74) Khoury, B., Lecomte, T., Fortin, G., Masse, M., Therien, P., Bouchard, V., Chapleau, M., 
Paquin, K. & Hofmann, S. G. (2013). Mindfulness-based therapy: a comprehensive meta-
analysis. Clinical psychology review, 33(6), 763-771.  
75) Van Dam N.T., et al (2018). Mind the hype: A critical evaluation and prescriptive agenda for 
research on mindfulness and meditation, Perspectives on Psychological Science. 13 (1), 2018, 
36-61. 
12 ATTACHMENT 
 

Consent Form: Bioscience 
 
 
 
 
 
 
 
 
Title of research study (clinical trial): Modulation effects of a novel body-mind intervention on subjective 
cognitive decline 
Investigator: Dr. Yi-Yuan Tang, College of Health Solutions 
Why am I being invited to take part in a clinical trial? 
We invite you to participate because you are healthy (free of any severe neurological and psychiatric diagnoses, having a 
self-reported cognitive decline) between 40 - 65 years old. Meanwhile, you are able to read/understand English and 
eligible for non-invasive fMRI, have normal or corrected-to-normal vision, weigh at least 110 lbs, and are willing to be 
randomized. 
Why is this clinical trial being done? 
Cognitive decline may involve deficits in self-control networks and integrative body-mind training (IBMT) could improve  
self-control, which may help reduce cognitive decline. The purpose of this study is to investigate brain and body  
mechanisms and the effects of reducing cognitive decline following IBMT. This work will improve our understanding of  
how training may affect brain, performance and behavior, and we are hopeful that it will have an eventual impact of  
preventing and reducing cognitive decline in this group. 
How long will the clinical trial last? 
We invite you to complete 5 onsite visits (each approximately 1 hour long). Visits will be scheduled roughly 1-6 months apart. 
The study is anticipated to spread across 12 months total (including 10 remote visits). 
How many people will be studied? 
We expect about 120 people. 
What happens if I say yes, I want to be in this clinical trial? 
It is up to you to decide whether or not to participate. Consenting to participate in this study will take place remotely 
over Zoom or by phone, prior to engaging in research activities.  
Eligibility Screen: you will be screened 5-10 min to make sure to meet the study eligibility criteria through Qualtrics or 
Redcap. If you meet criteria, you will be marked as “conditionally eligible” for study and move forward with the consent 
process on zoom. If not, participation in this clinical trial will stop at this time. 
Consenting: You will meet with the research staff on zoom to review the study consent form.  
There are 3 parts of this clinical trial:  
Part 1. Survey and tasks: You will complete questionnaires and tasks related to cognition, emotion and health through 
Qualtrics or Redcap (about 60 min). If you have technical issues with Qualtrics or Redcap, we will guide you either via 
Zoom or in person.  
Part 2. Five Brain MRI scans will occur at Barrow Neurological Institute (BNI) and consist of 5 visits about 1-6 months apart. 
For each of these visits, you will receive an MRI lasting no more than 60 minutes. During the MRI, you will be asked to watch 
a screen and complete some cognitive tasks or just close your eyes. You will interact with neuroimaging staff and Dr. Tang’s 
study staff. This study does not aim to provide diagnosis, if MRI shows an abnormality, MRI technologist may suggest you see 
a doctor. 
Part 3. Interventions: You will be randomly assigned to complete one intervention condition of this study (10 sessions with 
about 60 min/session). Interventions will be guided on zoom.  
We will ask for your permission to contact you for future studies; however, this is not necessary to participate in the 
current project. 
What happens if I say yes, but I change my mind later? 
You can leave at any time it will not be held against you. If you decide to leave, contact the investigator so that the 
investigator can terminate your participation. Already collected data may not be removed from the database.  

 
 
Is there any way being in this clinical trial could be bad for me? 
There is very little risk to you for participation in this study including questionnaires, MRI and interventions. As part of the 
fMRI scan, you will be continuously monitored throughout the scan. If you have claustrophobia or a pacemaker or some 
metal objects in your body, you will not be allowed to be in this study because of the strong magnetic fields in the MRI 
scanner. Another risk is the possibility of metal objects being pulled into the magnet and potentially hitting you. To 
eliminate this risk, you will need to remove anything metal from your clothes, any metal piercings, and anything metal from 
your pockets. You will also walk through a metal detector (like airport scanners) when you come into the magnet chamber. 
It is important to know that no metal can be brought into the magnet room at any time. Once you are in the scanner, the 
door to the room will be closed so that no metal from outside accidentally goes near the magnet.  If you are pregnant, you 
should delay your participation in this clinical trial. 
Will being in this study help me anyway? 
We cannot promise any benefits to you or others from your taking part in this clinical trial, and do not anticipate any direct 
benefits to you. However, the overall goal of this clinical trial is to improve our understanding of how training may affect brain, 
performance and behavior. Thus, there is a potential benefit to improve brain function and change behavior such as reducing 
cognitive decline through information gained in this project.  
What happens to the information collected for the clinical trial? 
Efforts will be made to limit the use and disclosure of your personal information to people who need to review this 
information. We cannot promise complete secrecy. Organizations that may inspect and copy your information include the 
Institutional Review Board and other representatives of this organization. The results may be used in reports, 
presentations, and publications but will not be reported back to you. If the results of the trial are published, your identity will 
remain confidential. For confidentiality purposes, your identity will be linked to a code number. A master list will be kept to 
link your name and the unique code number given to you. The master list, which contains your identity will be stored in 
secured computers and will be retained indefinitely. De-identified data collected as a part of the current clinical trial will not 
be shared with other investigators/industry sponsors for future research purposes. 
 
What else do I need to know? 
ASU Lab COVID-19 Procedures: 
• 
We are required to do symptom checks 24-48 hours prior to your appointment and will also perform another 
symptom check and temperature check using a touchless thermometer upon arrival at the lab 
• 
Lab disinfections are performed at the beginning and end of the lab work day by the research team and 
additional disinfections will be completed between your visits 
• 
Both research team and you are required to wear masks when inside ASU building and within ASU 
community spaces, if you forget to bring one to your appointment, we can provide a disposable mask 
• 
Only you will be permitted to enter the building. If needed, you may have one person accompany them to their 
appointments and will be subject to the same safety protocols. 
• 
We will minimize the number of people in the lab at a given time. We plan to have two researchers in the  lab 
with you – you face 1 researcher and 1 equipment faces 1 researcher 
• 
You will be asked to wash your hands and/or use hand sanitizer throughout the appointment. A hand sanitizing 
station is available in the lab 
 
ASU/BNI/Banner COVID-19 Procedures 
When conducting research visits at the Barrow Neurological Institute/Banner Health, all participants and research staff 
will be subject to/defer to the COVID procedures of the BNI Facilities, including, but not limited to temperature checks, 
COVID-19 health screening questionnaires, vaccination (when did you take vaccination and how many shots), etc. prior 
to entering the facility. Due to the nature of the assessments, the research team may need to be within 6 feet of the 
participant, for a period of time, for spotting purposes and/or to administer tests. To protect both the participant and 
research team, the following COVID procedures will be followed: 
• 
Both research team and you are required to wear masks during the assessments. 
• 
The research team plans to have no more than 3 research members present per visit, due to the different 
research specialty areas of the team, there may be two participant-facing researchers and one equipment- facing 
researcher. 
• 
You will be asked to wash your hands and/or use hand sanitizer throughout the appointment. 
• 
Equipment will be sanitized before and after use of each visit 
 
This research is being funded by the College of Health Solutions at ASU. If you agree to take part in this research study, 
after completion, we will pay you $300 for your time and effort. If you are getting more than $ 600 in 

 
 
a calendar year through your participation in research studies at ASU, we will reach out to you for additional information. If 
you do not complete the study, the payment will be prorated based on the time of task completed. If you are not eligible for 
the study, you will not receive payment. If you agree to participate, then consent does not waive any of your legal rights. 
However, no funds have been set aside to compensate you in the event of injury. In the event of an injury or illness during 
any clinical evaluation, experimental session, or training session, 911 will be called and/or you will be directed to a nearby 
medical emergency facility. You will be responsible for the costs for any emergency services that are offered. If you think you 
have suffered a research-related injury, you should promptly notify the Principal Investigator listed in the Contact Information 
below. Any adverse event will be reported by the project PI to ASU IRB within 24 hours. A description of this clinical trial will 
be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can 
identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. 
Who can I talk to? 
If you have questions, concerns, or complaints, or think the research has hurt you, talk to the principal investigator 
480-790-3577 (Yi-Yuan Tang), or yiyuan@asu.edu (Yi-Yuan Tang) 
This clinical trial has been reviewed and approved by the Bioscience IRB (“IRB”). You may talk to them at (480) 965-6788 or 
research.integrity@asu.edu if: 
· 
Your questions, concerns, or complaints are not being answered by the research team 
· 
You cannot reach the research team. 
· 
You want to talk to someone besides the research team. 
· 
You have questions about your rights as a research participant. 
· 
You want to get information or provide input about this clinical trial. 
 
Signature Block for Capable Adult 
Your signature documents your permission to take part in this clinical trial. 
 
 
 
Signature of participant 
 
Date 
 
 
Printed name of participant 
 
 
 
Signature of person obtaining consent 
 
 
 
Date 
                   Printed name of person obtaining consent