Motor Imagery Intervention for Improving Gait and Cognition in the Elderly
Phase: NA
Conditions: Motor Activity
Sponsor: Albert Einstein College of Medicine

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MI-Intervention Protocol, Version 1.0
Motor Imagery: A Pilot Intervention for 
Improving Gait and Cognition in the 
Elderly
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017

MI-Intervention Protocol, Version 1.0
PROTOCOL AND MOP MODIFICATIONS/AMENDMENTS
Description of change
Date
Document 
name & Page #
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017

MI-Intervention Protocol, Version 1.0
Motor Imagery: A Pilot Intervention for Improving Gait and Cognition in the 
Elderly
Principal Investigators:
Helena M. Blumen, PhD
Joe Verghese, MBBS (mentor) 
Departments of Medicine and Neurology, Albert Einstein College of Medicine, Bronx, NY.
Supported by:
The National Institute on Aging
1 K01 AG049829-01A1
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017

MI-Intervention Protocol, Version 1.0
Version 1
January 6th, 2017
TABLE OF CONTENTS
Page
Protocol and MOP MoDIFICATIONS/amendments..................................................................i
TABLE OF CONTENTS.............................................................................................................iii
PRÉCIS..........................................................................................................................................iv
Study Title ..................................................................................................................................iv
Design and Outcomes.................................................................................................................iv
Interventions and Duration ..........................................................................................................v
Sample Size and Population ........................................................................................................v
STUDY TEAM ROSTER .............................................................................................................1
Principal Investigator:..................................................................................................................1
Mentor: ........................................................................................................................................1
Co-Mentors:.................................................................................................................................1
Statistical Consultation:...............................................................................................................2
1
Study objectives .....................................................................................................................3
1.1
Primary Objective............................................................................................................3
1.2
Secondary & Tertiary Objectives ....................................................................................3
2
BACKGROUND AND RATIONALE .................................................................................3
2.1
Background......................................................................................................................3
2.1
Study Rationale................................................................................................................3
3
STUDY DESIGN ...................................................................................................................4
4
SELECTION AND ENROLLMENT OF PARTICIPANTS.............................................5
4.1
Inclusion Criteria .............................................................................................................5
4.2
Exclusion Criteria ............................................................................................................6
4.3
Study Enrollment Procedures ..........................................................................................6
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5
STUDY INTERVENTIONS .................................................................................................6
5.1
Interventions, Administration, and Duration...................................................................6
5.2
Handling of Study Interventions......................................................................................8
5.3
Concomitant Interventions...............................................................................................8
5.3.1
Allowed Interventions .................................................................................................8
5.3.2
Required Interventions.................................................................................................8
5.3.3
Prohibited Interventions...............................................................................................8
5.4
Adherence Assessment ....................................................................................................8
6
STUDY PROCEDURES .......................................................................................................9
6.1
Schedule of Evaluations ..................................................................................................9
6.2
Description of Evaluations ............................................................................................10
6.2.1
Screening Evaluation.................................................................................................10
6.2.2
Enrollment, Baseline, and Randomization ................................................................11
6.2.3
Follow-up Visits ........................................................................................................11
6.2.4
Completion/Final Evaluation.....................................................................................11
7
SAFETY ASSESSMENTS..................................................................................................12
7.1
Specification of Safety Parameters................................................................................12
7.2
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters.....12
7.3
Adverse Events and Serious Adverse Events ................................................................13
7.4
Reporting Procedures.....................................................................................................14
7.5
Follow-up for Adverse Events.......................................................................................14
7.6
Safety Monitoring..........................................................................................................14
8
INTERVENTION DISCONTINUATION ........................................................................15
9
STATISTICAL CONSIDERATIONS...............................................................................15
9.1
General Design Issues....................................................................................................15
9.2
Sample Size and Randomization ...................................................................................17
9.2.1.
Treatment Assignment Procedures........................................................................17
9.3
Interim analyses and Stopping Rules.............................................................................18
9.4
Data Analyses ................................................................................................................18
9.4.1
Primary outcome........................................................................................................18
9.4.2. Secondary and tertiary outcomes.................................................................................18
10
DATA COLLECTION AND QUALITY ASSURANCE .................................................19
10.1
Data Collection Forms...................................................................................................19
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10.2
Data Management..........................................................................................................20
10.3
Quality Assurance..........................................................................................................20
10.3.1
Training..................................................................................................................20
10.3.2
Quality Control Committee ...................................................................................20
10.3.3
Metrics ...................................................................................................................20
10.3.4
Protocol Deviations ...............................................................................................21
10.3.5
Monitoring .............................................................................................................21
11
PARTICIPANT RIGHTS AND CONFIDENTIALITY ..................................................22
11.1
Institutional Review Board (IRB) Review ....................................................................22
11.2
Informed Consent Forms ...............................................................................................23
11.3
Participant Confidentiality.............................................................................................23
11.4
Study Discontinuation ...................................................................................................23
12
ETHICAL CONSIDERATIONS .......................................................................................23
13
COMMITTEES ...................................................................................................................23
14
PUBLICATION OF RESEARCH FINDINGS.................................................................23
15
REFERENCES ....................................................................................................................23
16
SUPPLEMENTS/APPENDICES .......................................................................................28
I. Informed Consent Form 
 
III. Adverse Event and Serious Adverse Event Forms
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PRÉCIS
Study Title
Motor Imagery: A Pilot Intervention for Improving Gait and Cognition in the Elderly
Objectives:
Primary. Compared to a visual imagery intervention group, participants who are enrolled in the
motor imagery intervention (MI) group will demonstrate:
P1: Significant improvements in gait speed during actual Walking and Walking While Talking
Secondary. Compared to a visual imagery intervention group, participants who are enrolled in the
motor imagery intervention (MI) group will show:
P 2.1: Significant improvements in cognitive performance during Talking and Walking While
Talking
P 2.2: Change in blood-oxygen-level dependent signal during Walking and Walking While
Talking
Design and Outcomes  
The investigators propose to conduct a single-blind randomized clinical trial to test the efficacy
of a phone-based motor imagery intervention for improving gait and cognition in older adults
between 65 and 85 years old
Post-Intervention Assessments
Randomize
Motor Imagery (12 weeks)
Visual Imagery (12 weeks)
Inivite Eligible Participants for
Baseline Assessment
Identify participants 65-85 years old
Administer Telephone Screening
Figure 1. Participant Flow
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Interventions and Duration 
Participants will be randomized into either a 12-week phone-based motor imagery intervention or 
visual imagery intervention (active control condition). Both groups will complete 36 (15-minute) 
sessions (9 hours). 
Participants will receive gait, mobility, cognitive and neuroimaging assessments at baseline and 
post-intervention (14-18 weeks after intervention). Baseline and post-intervention assessments 
will last about 3 hours over 1 day.
Sample Size and Population 
We will enroll 48 cognitively-healthy older adults (24 in each group). 
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STUDY TEAM ROSTER 
Principal Investigator: 
Helena M. Blumen
Einstein College of Medicine,
1225 Morris Park Avenue, Van Etten 313 B, Bronx, NY 10461
Telephone: 718 430 3810
Fax: 718 430 3829
helena.blumen@einstein.yu.edu
Main responsibilities/Key roles: She will coordinate efforts between team members, supervise 
implementation of study measures and supervise data collection. She will develop data analysis 
plans as well as scientific presentations and manuscripts based on the research findings.
Mentor:
Joe Verghese
Albert Einstein College of Medicine,
1225 Morris Park Avenue, Van Etten 308, Bronx, NY 10461
Telephone: 718 430 3808
Fax: 718 430 3829
joe.verghese@einstein.yu.edu
Main responsibilities/Key roles: He will be responsible for the oversight of Dr. Blumen's 
responsibilities and for establishing benchmarks to ensure successful completion of this 
intervention. He will also be involved in developing data analysis plans as well as scientific 
presentations and manuscripts based on the research findings.
Co-Mentors: 
Christian Habeck,
Columbia University Medical Center
710 West 168th Street, 18th floor, New York, NY 10032
Telephone: 212 305-6939
ch629@cumc.columbia.edu
Main responsibilities/Key roles: He will help develop neuroimaging data analysis plans as well as 
scientific presentations and manuscripts based on the research findings.
Roee Holtzer
Albert Einstein College of Medicine,
1225 Morris Park Avenue, Van Etten 311, Bronx, NY 10461
Telephone: 718 430 3962
Fax: 718 430 3829
Roee.holtzer@einstein.yu.edu
Main responsibilities/Key roles: He will help develop behavioral data analysis plans as well as 
scientific presentations and manuscripts based on the research findings.
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Statistical Consultation:
Cuiling Wang
Albert Einstein College of Medicine
1300 Morris Park Avenue, Block 314, Bronx, NY 10461 
Telephone: 718 430 2006
Fax: 718 430 3829
Cuiling.wang@einstein.yu.edu
Main responsibilities/Key roles: Dr. Wang will provide statistical consultation and provide input 
regarding data management, security, and randomization processes for the clinical trial.
 
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1
STUDY OBJECTIVES
1.1
Primary Objective
Compared to a visual imagery intervention group, the participants who are enrolled in the motor 
imagery intervention group will demonstrate significant improvements in gait speed (cm/s) during 
actual Walking and Walking While Talking using an instrumented walkway (GAITRite® 
electronic walkway system). 
1.2
Secondary & Tertiary Objectives
Compared to a visual imagery intervention group, the participants who are enrolled in the motor 
imagery intervention group will show: 
•
Significant improvements in cognitive performance during Talking and Walking While 
Talking
•
Changes in blood-oxygen-level dependent signal during Walking and Walking While 
Talking
•
Improvement in executive function, and other mobility-related cognitive processes, such 
as speed of processing, memory and spatial navigation. 
•
Improved gait variability and other quantitative gait parameters during walking and 
walking while talking. 
2
BACKGROUND AND RATIONALE 
2.1 Background 
Age-related gait decline is common among the elderly; with over a third of community-residing 
elders having clinically diagnosable gait abnormalities. Gait impairment in the elderly is associated 
with an increased risk of falls, morbidity, hospitalization, mortality, cognitive decline, and 
dementia (1-5). Physical exercise programs can be used to improve gait in the elderly, but long-
term adherence to physical exercise programs is low, and particularly difficult to implement in the 
elderly (6-8). Determining the efficacy of motor imagery for improving gait and cognition may 
provide scientific support for a future large-scale randomized controlled trial to establish and 
contrast the independent and combined roles of physical and imagined exercises to prevent 
mobility disability.
2.1
Study Rationale
Motor imagery involves envisioning motor actions without actual execution, and has been 
successfully used by athletes to improve athletic performance for quite some time; for reviews see 
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(9-12). There is some evidence that motor imagery can be used to improve gait, gait-related and 
cognitive functions in Parkinson's disease (13-15) and post stroke (16-20), but the rehabilitative 
potential of motor imagery in relatively healthy elderly is currently unknown.
Recent research suggests that gait engages a distributed network of brain regions including motor, 
basal ganglia, cerebellar and supplementary motor regions. Based on recent findings by us (21) 
and others (22, 23), we hypothesize that imagined gait can be used as a rehabilitative tool for 
improving gait in the elderly because it engages and strengthens similar neural systems as actual 
gait. Age-related gait decline is particularly evident in dual-task situations that demand Executive 
Functions (EF) and engage the prefrontal cortex (24-31). We recently developed and validated an 
imagined gait protocol against an actual gait protocol that involves an ecologically-valid dual-task 
situation (walking while talking; WWT) that predicts falls, frailty, disability and mortality in the 
elderly (21, 31, 32). This imagined gait protocol involves: 1) imagined Walking (iW), imagined 
Talking (iT) and imagined Walking While Talking (iWWT), 2) is associated with actual WWT 
performance, and 3) permits us to examine the underlying neural systems of gait with functional 
magnetic resonance imaging (fMRI). We have identified a pattern of brain regions whose 
activation change as a function of imagery task difficulty (iW < iT< iWWT), and is associated 
with actual WWT performance (21). Increases were most notably observed in cerebellar, 
precuneus, supplementary motor and prefrontal cortex regions. These initial findings suggest that 
our imagined gait protocol engages similar neural systems as actual gait and EF and command the 
development of this protocol into a tool for improving gait and EF in the elderly. 
The first aim of this research is to establish the efficacy of this imagined gait protocol to improve 
gait and EF in the elderly. We propose a pilot Randomized Clinical Trial (RCT) of 48 cognitively-
healthy elderly adults who will be randomly assigned to an imagined gait intervention or an Active 
Control (AC; non-mobility related visual imagery) condition. The imagined gait (or AC) protocol 
will be administered during each study visit, and over the phone three times a week for three 
months (15 min/session, total of 36 sessions). Each participant will complete two study visits (pre 
and post). Pre-post intervention changes in gait velocity (cm/s) and cognitive performance (percent 
of correct letters provided; (correct/error x correct) x 100) during actual W, T and WWT will be 
our primary outcome measures. Age, Sex and Education will be covariates in all analyses. Other 
variables/covariates will be recorded (e.g. medical illnesses and history of falls), and carefully 
examined for potential inclusion as covariates in upcoming full-scale RCT.  
The second aim is to determine neuroplasticity changes in response to our imagined gait 
intervention. To this end, participants will complete the imagined gait protocol (iW, iT and iWWT) 
during fMRI scanning at the pre and post-intervention study visits.  We predict that our imagined 
gait protocol engages neural systems linked to actual gait and EF, while the AC condition engages 
neural systems linked to visual processing and imagery in general. We further predict that the 
neural systems engaged during our imagined gait protocol are strengthened following our 
imagined gait intervention. 
3
STUDY DESIGN
Design: We propose a single-blind study of cognitively-healthy older adults randomized to a 
phone-based motor imagery or visual imagery (active control) intervention for 12 weeks (36 
sessions)
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Outcomes: The primary outcome is post-intervention change in gait speed during actual walking 
and walking while talking.   
Secondary and tertiary outcomes include improvements in cognitive performance during Talking 
and Walking While Talking, changes in blood-oxygen-level dependent signal during Walking and 
Walking While Talking, improvement in executive function, and other mobility-related cognitive 
processes (speed of processing, memory and spatial navigation), and improved gait variability and 
other quantitative gait parameters during walking and walking while talking (see 
Clinicaltrials.gov-NCT02762604 for a comprehensive list). 
Study population: 48 Bronx and Westchester county residents between 65 and 85 years old will be 
randomized into a phone-based motor imagery or visual imagery (control) intervention for 12 
weeks (36 sessions)
Study location: Pre and post-intervention visits will be held at the Albert Einstein College of 
Medicine.
Approximate duration of enrollment period and follow-up: Potential recruits who meet eligibility 
criteria on the telephone are invited to baseline assessment and then randomized to motor imagery 
or visual imagery intervention. Baseline study assessments are limited to 180 minutes over 1 day 
to avoid fatigue. Telephone assessments are 15 minutes. Post-intervention assessments will be 
conducted within 4 weeks of the completion of the intervention. 
We plan to enroll and randomize 48 participants over 36 months (1-2 per month). If necessary, we 
will ask for a no cost extension to allow for additional time to process and analyze the data, write 
manuscripts, and possibly apply for a follow-up grant. 
Randomization and Blinding: We will include a number of methods to reduce bias. 
•
Selection bias will be reduced by concealing treatment allocation until the participant is entered 
into trial.
•
Primary outcome is an objective endpoint (gait speed) and not subjective mobility complaints.
•
Motor imagery and visual imagery interventions will be administered individually, and at non-
overlapping times.
•
Participants and study staff will be instructed not to disclose group assignment or details of 
interventions.
•
Study staff that administers baseline and post-intervention assessments will be different from 
those that administer the phone-based motor imagery and visual imagery interventions.  
4
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1
Inclusion Criteria 
•
Adults between 65 and 85 years and older, residing in the community.
•
Able to speak English at a level sufficient to undergo study procedures.
•
Plan to be in the area for the next 3 months.
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4.2
Exclusion Criteria 
•
Presence of dementia (telephone-based memory impairment screen < 5 or AD-8 score > 
1).
•
Presence of gait disorder diagnosed by clinician (e.g. neuropathy).
•
Any medical condition or chronic medication use (e.g. neuroleptics) that will compromise 
safety or affect cognitive functioning.
•
Terminal illness with life expectancy <12 months.
•
Progressive, degenerative neurologic disease (e.g. Parkinson's disease, ALS).
•
Major psychiatric disorders such as Schizophrenia.
•
Pacemaker or any permanent metal implants like hip prosthesis (other than tooth fillings) 
and claustrophobia.
•
Participation in other intervention trial or observational studies during the intervention 
period.
4.3
Study Enrollment Procedures 
Participants will be recruited from the Bronx and Westchester areas. A letter explaining our study 
will be sent and followed by a telephone call a few days later. Those expressing interest will be 
screened with the Telephone MIS (33) (sensitivity 85%, specificity 86%) and AD-8 (34, 35) 
(sensitivity 74%, specificity 86%). 
Baseline visit: Eligible participants are invited for baseline assessments. Written consent and 
baseline assessments will occur in our research center. On arrival, potential participants will review 
study information and sign consent. Eligible subjects will be randomly assigned to an intervention 
group after completing baseline assessments.
All reasons for ineligibility and for non-participation will be documented in the database.
Following the completion of baseline assessments, participants will be randomly assigned to either 
the motor imagery or visual imagery interventions. Group assignment will be displayed to RAs 
from a generated list using sequential study numbers so that the assistant who enrolls the 
participants will be blinded to randomization assignment of the next participant until assigned.
5
STUDY INTERVENTIONS 
5.1
Interventions, Administration, and Duration 
During gait imagery training, participants will be trained to iW, imagine talking (iT: reciting 
alternate letters of the alphabet out loud) and iWWT. They will be instructed to close their eyes 
during imagery, use both visual and kinesthetic imagery, and pay equal attention to both tasks in 
the iWWT condition. Seated at a desk, they will then complete two trials of imagery training in 
16-seconds blocks for approximately 15 minutes. Imagery instructions will be presented auditorily, 
and the beginning and the end of a block will be initiated with a tone. During the first trial, 
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instructions will be detailed (i.e. “Imagine Walking: At the start of the next tone, close your eyes 
and imagine or envision yourself walking on the mat. At the start of the following tone, stop, and 
wait for further instructions”), but during the second trial they will simply prompted to begin at 
the start of the tone (e.g. “Imagine Walking”). Following each trial, participants will be asked to 
evaluate the quality of their visual and kinesthetic images on a scale from 1 (no image; no 
sensation) to 5 (image as clear as seeing; as intense as executing the action). During visual 
imagery training, participants will be trained to imagine a set of concrete objects (e.g. giraffe) 
from a standardized set of pictures (36) that have been normed for name agreement, image 
agreement and visual complexity. Again, they will be instructed to close their eyes during imagery 
and will complete two trials of imagery training in 16 second blocks for approximately 15 minutes. 
Imagery instructions will be presented auditorily and the beginning and the end of a block will be 
initiated with a tone. Following each trial participants will be asked to evaluate the quality of their 
visual and kinesthetic images on a validated scale from 1 to 5 (37, 38). 
During the imagined gait protocol (in MRI), imagery prompts (e.g. imagine walking) will be 
presented auditorily and volume will be adjusted to ensure instructions can be heard clearly in the 
presence of scanning noise. Imagery will occur in 16-second blocks (eyes closed). A tone will 
indicate the beginning and the end of a block, and each block will be repeated six times. Following 
the imagery task, participants will again be asked to evaluate the overall quality of their visual and 
kinesthetic images on a 1-5 scale. During the visual imagery protocol (in MRI), imagery prompts 
(e.g. imagine a giraffe) will be presented auditorily and volume adjusted to ensure instructions 
could be heard clearly in the presence of scanning noise. Again, imagery will occur in 16-second 
blocks (eyes closed). A tone will indicate the beginning and the end of a block, and each block 
will be repeated six times. 
During the imagined gait intervention, participants will be called by the experimenter three times 
a week and be asked to iW, iT and iWWT following the same protocol as during their study visit. 
They will also be asked to rate their visual and kinesthetic qualities of their images on a 1-5 scale 
(37, 38) following each trial. During the active control intervention, participants will be called 
three times a week by the experimenter and be asked to imagine concrete objects following the 
same protocol as during their study visit. Participants will be contacted over the phone on Monday, 
Wednesday and Friday mornings (before 12 noon), unless other times or days are preferred. Calls 
will be made to a landline (unless cellphone is the only option for a particular participant), and 
participants will be instructed to sit down comfortably, and turn down any distracting noise (e.g. 
music or TV). If a participant is unavailable at the scheduled time, we will try to reach them later 
in the day, but if we are still unsuccessful, we will skip that particular session and wait until the 
next scheduled session. Any unexpected distractions or missed sessions will be carefully recorded, 
and examined to inform the development of full-scale RCT.      
Performance monitoring and dose: The imagined gait and active control interventions will be 
administered by a designated RA in our research center under controlled conditions to protect 
internal validity of the study and to ensure compliance with protocol.  Participants will also be 
instructed to take a seat and turn down any distracting noise (such as the radio or TV) before 
beginning each session. Following each 15-minute session, the visual and kinesthetic qualities of 
the images will be tracked to ensure that participants are fully engaged during each session. 
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Tracking imagery performance in this manner will also be informative to assess dose response 
effects, which will help in the design of future studies.
Frequency and duration: We propose a 36 session phone-based motor imagery or active control 
intervention over 12 weeks. Our intervention is of longer duration and greater intensity than most 
prior studies.  Each training session takes 15 minutes to complete. Total training time over 12 
weeks is 540 minutes. We can track performance to assess dose response effects, which will help 
in the design of future studies.
5.2
Handling of Study Interventions 
Both interventions will be administered in doses of approximately 45 minutes (three 15-minute 
sessions) per week for 12 weeks without crossover at our facilities. Each intervention session will 
be supervised by Drs. Blumen and/or Dr. Verghese.  
5.3
Concomitant Interventions
5.3.1
Allowed Interventions
N/A
5.3.2
Required Interventions 
N/A
5.3.3
 Prohibited Interventions
Participants will not be allowed to participate in any other intervention or observational 
studies while enrolled in the intervention phase of this trial
5.4
Adherence Assessment 
Sustaining adherence represents a major challenge in any RCT involving older adults. The phone-
based delivery of the RCT improves likelihood of adherence. We have also incorporated multiple 
methods to promote adherence and reduce possibility of missing data. 
•
A permanent staff contact will be provided for each participant in the motor imagery and visual 
imagery intervention groups. 
•
Transportation and snacks will be provided on pre and post intervention assessment days.  
•
All participants will be compensated for attending in-house or telephone sessions ($50 for the 
baseline visit, $25 for the phone-based intervention, and $50 for the post-intervention visit, for 
a total of $125 for the study).
We propose to over-enroll by 20% to account for any attrition. Methods to account for non-
compliance and missing data:
•
Protocol violations. Subjects who miss 6 sessions due to any reason will be excluded from 
main analyses. We will explore dose response by adjusting number of sessions attended as a 
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covariate.
•
We will identify 2 contact persons who do not live with the participant for when participant 
cannot be reached.
•
Flexible scheduling with makeup sessions on alternate days. 
•
For each in-house study visit, we will allow a four-week window for completion.
•
If the participant is acutely ill, is in the hospital, or has a temporary condition that interferes 
with walking (e.g. ankle sprain), we will attempt to complete the assessment at another time. 
•
Outcome adjudication. The research team will adjudicate events such as mobility disability in 
subjects who drop out based on medical interviews, contact interviews, and home assessments 
as required.
6
STUDY PROCEDURES
6.1
Schedule of Evaluations
Pre-Intervention
During 
Intervention
Post-
Intervention
Measures 
Test/Type
Visit
Baseline week 0
weeks 1-12
Post week 12-16
Verbal consent
Consent
Phone    
Demographic/Health Screen
Screen
Phone    
Memory Impairment Screen
Screen
Phone    
AD-8 Dementia Screening Interview
Screen
Phone    
Handedness
Screen
Phone    
MRI safety (verbal)
Screen
Phone    
Informed Consent
Consent
Study Visit

MRI safety (paper)
Screen
Study Visit


Baseline Medical history
Survey
Study Visit

Sensory Screen 
Physical
Study Visit

Medications
Survey
Study Visit

Height/Weight/BMI
Physical
Study Visit


Blood Pressure
Physical
Study Visit


SPPB
Physical/Gait
Study Visit


Maze
Cognitive/Gait
Study Visit


Berg Balance Scale
Physical/Gait
Study Visit


Unipedal Stance
Physical/Gait
Study Visit


Stair climbing 
Physical/Gait
Study Visit


Grip Strength
Physical/Gait
Study Visit


WRAT & WTAR
Cognitive
Study Visit


RBANS figure copy & delay
Cognitive
Study Visit


Free Cued Serial Recall Test
Cognitive
Study Visit


Falls Questions
Survey
Study Visit/Phone



Falls Efficacy Scale
Survey
Study Visit


Duke Activity Status Index
Survey
Study Visit


Trails A & B
Cognitive
Study Visit


Control Oral Word Association Test
Cognitive
Study Visit


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Semantic Fluency
Cognitive
Study Visit


General Mobility Questionnaire
Survey
Study Visit


Geriatric Depression Scale (GDS-30)
Survey
Study Visit


Instrumental ADL Questionnaire
Survey
Study Visit


Flanker Interference 
Cognitive
Study Visit


WAIS Digit Symbol Substitution Test
Cognitive
Study Visit


Stroop Interference
Cognitive
Study Visit


Activity Balance Confidence Scale
Survey
Study Visit


SF-12
Survey
Study Visit


CHAMPS 
Survey
Study Visit/Phone

 

Letter Number Sequencing
Cognitive
Study Visit


Social Network Index
Survey
Study Visit


Beck Anxiety Inventory
Survey
Study Visit


MOS Social Support Survey
Survey
Study Visit


Gait Rite 
Physical/Gait
Study Visit


Imagery Protocol
Study Visit


6.2
Description of Evaluations 
6.2.1
Screening Evaluation
Consenting Procedure
A letter explaining our study will be sent and followed by a telephone call a few days 
later. Those expressing interest will be screened using a structured telephone interview 
to obtain verbal consent. Potential recruits will then be screened over the phone, and 
those who meet eligibility criteria will be scheduled for their first study visit. They will 
also be told that they will receive a phone call reminder the evening before their 
appointment. Written consent will occur in our research center and conducted by 
trained RAs. On arrival, potential participants will review study information and sign 
consent. Consenting will take place prior to any assessments. 
All consent forms will be stored in a locked file with other study documents and 
records. See approved Consent form in Appendix I.
Screening  
Potential recruits who meet eligibility criteria on the telephone are invited to schedule 
their first study session, and are told that they will receive a phone call reminder the 
evening before the appointment. 
Telephone screening: A letter explaining our study will be sent, followed by a 
telephone call a few days later. Those expressing interest will be screened over the 
phone prior to enrollment.   Telephone screening responses will also be reviewed and/or 
repeated (e.g. MRI safety) during the first study session to ensure eligibility prior to 
other study procedures. Inclusion criteria are: 1) age 65-85 years old 2) able to speak 
English at a level sufficient to undergo study procedures, and 3) plan to be in the area 
for the next 3 months. Exclusion criteria are: 1) Presence of dementia (telephone-based 
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memory impairment screen MIS < 5 or AD-8 score >, 2) Presence of gait disorder (e.g. 
neuropathy), progressive neurodegenerative disease (e.g. Parkinson’s disease) or major 
psychiatric disorder (e.g. Schizophrenia), 3) MRI contraindication (e.g. pacemaker), 4) 
participation in other interventional or observational study during the study period, and 
5) any medical condition or chronic medication use (e.g. neuroleptics) that will 
compromise safety or affect cognitive functioning.
6.2.2
Enrollment, Baseline, and Randomization
Enrollment
The enrollment date is defined as the date that the participants are randomized into 
either the motor imagery or visual imagery intervention, after they have met all 
screening criteria and agreed to participate. 
Baseline Assessments
For participants who have successfully been screened for eligibility, baseline 
assessments are performed during their first study session. 
Randomization
Randomization will be determined after completion of the baseline assessments. 
Initiation of the study intervention will take place in the week following the baseline 
assessment visit.   
6.2.3
Follow-up Visits 
Post intervention follow-up assessments will occur within 4 weeks of the completion 
of the intervention. In addition adverse events will be evaluated over the phone 
throughout the intervention and at the post-intervention visits. A 4-week window will 
be allowed for each of the post-intervention assessments.  
6.2.4
Completion/Final Evaluation
Assessments to be completed at the final visit (12 months post-intervention) are listed in 
Table 5.1.
Losses to follow-up can be classified into non-informative (missing at random (MAR)) 
and informative censoring (drop out depends on the unobserved outcomes). No 
adjustment is necessary for non-informative censoring. However, for informative 
censoring, parameter estimates and resulting tests on hypotheses will be biased without 
further adjustment. The best way to handle missing data is to avoid it. However, we 
recognize that despite all our efforts there will be missing data. 
Dropouts: We will follow-up with participants who dropped out of the study to determine 
both their mobility status and reasons for withdrawal. The research team will adjudicate 
events such as mobility disability in subjects who drop out based on medical interviews, 
contact interviews, and home assessments as required. Utilization of the telephone based 
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questionnaire to account for possible non-random drop-out will be administered. If the 
participant is acutely ill, is in the hospital, or has a temporary condition that interferes 
with walking (e.g. ankle sprain), we will attempt to complete the assessment at another 
time. 
We also propose intention to treat (ITT) analysis, which includes all randomized 
participants in the groups assigned, regardless of their adherence with the entry criteria, 
whether motor imagery was received, and subsequent withdrawal or deviation from the 
protocol. ITT analysis is pragmatic because it admits noncompliance and protocol 
deviations, and gives an unbiased estimate of the intervention effect. Handling missing 
data is a major issue in ITT, and is dealt with by imputation or sensitivity analysis. Our 
statistician, Dr. Wang, is very experienced in these methods. 
A rich set of telephone-based information will be collected even for those subjects who 
may drop out. We will utilize this auxiliary information to assess the MAR assumption 
and combine it into the main model through joint modeling and multiple imputation 
approaches.  Dr. Wang has applied these approaches to eliminate or reduce bias in 
presence of informative censoring in our other aging studies.
7
SAFETY ASSESSMENTS 
7.1
Specification of Safety Parameters
The research staff and investigators will be present during all testing. All questionnaire 
completion will be done at a slow enough pace so as not to tire individuals. If subjects 
express physical or mental tiredness or discomfort during any of the assessments or training 
procedures, the procedure will be terminated immediately. Drs. Blumen and Verghese will 
be available onsite or cell at all times to address any safety concerns or clinical issues 
during the interventions.
All abnormal findings from the clinical, mobility, neuroimaging, and neuropsychological 
assessments done on baseline, screening visits, and post-intervention visits will be 
documented and reviewed by the DSMB chair. Periodic audits from the Albert Einstein 
College of Medicine IRB ensure compliance with confidentiality guidelines and adverse 
events monitoring.
7.2
Methods and Timing for Assessing, Recording, and Analyzing Safety Parameters
Answering health questionnaires and mental state examinations involve minimal 
psychological, social, or other risks. We do not expect any serious adverse events during 
these non-invasive tests and training programs of attention and executive function. The 
motor imagery and visual imagery interventions involve mental but no physical effort by 
the participants. Some people are bothered by feelings of confinement (claustrophobia), 
and by the noise made during MRI. Participants will be asked to wear earplugs or earphones 
while in the MRI machine. They may not participate in this study if they have a pacemaker, 
an implanted defibrillator or certain other implanted electronic or metallic devices.
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7.3
Adverse Events and Serious Adverse Events 
An adverse event (AE) is defined as any untoward or unfavorable medical occurrence in 
a human subject, including any abnormal sign (for example, abnormal physical exam), 
symptom, or disease, temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research. Adverse 
Events encompass both physical and/or psychological harms. AEs will be documented on 
forms (See Appendix II).
A serious adverse event (SAE) is defined as any untoward medical occurrence that results 
in death, is life threatening, requires inpatient hospitalization or prolongation of existing 
hospitalization, results in persistent or significant disability/incapacity, or is a congenital 
anomaly. SAEs will be documented on SAE forms (Appendix II).
Unanticipated Problem (UP): Any event, deviation, or problem, that is unexpected; AND 
possibly, probably or definitely related to study participation; AND serious.
a. Unexpected: An event can be categorized as unexpected if it occurs in one or more 
subjects participating in a research protocol; and the nature, severity, or frequency of 
which is not consistent with either:
i. The known or foreseeable risk of adverse events associated with the 
procedures involved in the research that are described in protocol-related 
documents such as: the IRB-approved research protocol; any applicable 
investigator brochure: the current IRB-approved informed consent document; or 
other relevant sources of information, such as product labeling and package 
inserts; or
ii. The expected natural progression of any underlying disease, disorder, or 
condition of the subject(s) experiencing the adverse event and the subject’s 
predisposing risk factor profile for the adverse event.
b. Serious: An adverse event or suspected adverse reaction is considered "serious" if, 
in the view of either the investigator or sponsor, it results in any of the following 
outcomes:
i. death,
ii. a life-threatening adverse reaction,
i. inpatient hospitalization or prolongation of existing hospitalization,
ii. persistent or significant disability/incapacity,
iii. a congenital anomaly/birth defect,
iv. or based upon appropriate medical judgment, may jeopardize the subject’s 
health and may require medical or surgical intervention to prevent one of the 
other outcomes listed in this definition (examples of such events include allergic 
bronchospasm requiring intensive treatment in the emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or 
the development of drug dependency or drug abuse).
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Protocol Deviation (PD): Any change in the processes or procedures of research that 
were not approved by amendment of an IRB-approved protocol.
7.4
Reporting Procedures
An internal log of all AE, SAE, UP and PD events that come to the attention of the staff 
will be maintained. 
Unanticipated Problems will be reported to the IRB using the Reportable Events Form 
within 5 business days of the identification of the event by the research staff.
RAs will maintain a daily attendance log throughout the intervention. If a participant is not 
in attendance at any of the sessions it will be recorded and they will attempt to get in touch 
with the participant. If it comes to their attention that an adverse even has taken place they 
will document this on the attendance log and fill out an AE form and/or SAE form if 
necessary. All adverse events will be compiled and reported on an ongoing basis and in 
summary form at the conclusion of the study to the IRB, the DSMB medical officer (Dr. 
Bean) and the NIA program officer (Dr. St. Hillaire-Clarke).  Unanticipated (non-serious) 
adverse events will be reported within 30 days via submission of an Adverse Event Report.  
Serious adverse events will be reported within 24 hours by phone, email or fax. A 
completed Adverse Event Report will be submitted within 10 days of initial notification.  
All deaths will be reported within 24 hours.
If PIs become aware of issues that threaten the integrity of the trial or participant safety, 
they will alert the NIA representative to the DSMB who will consult with the DSMB Chair 
as to whether a special meeting or conference call of the DSMB should be held.
7.5
Follow-up for Adverse Events
AEs will be followed until resolved or considered stable.
7.6
Safety Monitoring
Prior to beginning data collection, Dr. Blumen and the DSMB Chair will reconfirm that 
our site has appropriate safety measures in place. The DSMB will meet with the entire 
research team to review the study protocols. Particular attention will be paid to outcome 
definition, study design, procedures for recording and reporting adverse events, and 
informed consent procedures and documentation. 
At the initial meeting, the DSMB may recommend modifications or clarification of the 
protocol, and it will formulate its operating procedures (e.g., meeting schedule, reports due 
dates for the study statistician, unblinding policy, and what interim data may be released 
to the investigators). At the initial meeting the plans for interim monitoring for efficacy 
and futility will be presented to the DSMB as an aid for monitoring the trial. 
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We will train competent staff to conduct the interventions and assessments, ensure they 
understand the nature of the interventions, and understand adverse event reporting 
requirements. Trained clinical assistants, who will monitor the subject for any adverse 
events, will perform all assessments.  We do not expect any serious adverse events during 
these non-invasive interventions. The clinical assistant will stop the testing procedures if 
subjects feel stressed or get embarrassed by their performance, and relay the information 
immediately to Dr. Blumen or Verghese.  At least one investigator will be present onsite 
during all testing and intervention sessions.  In addition Drs. Blumen and Verghese will be 
available by cellular telephone at all times to address any safety concerns or clinical issues.
Please see the Safety Monitoring Guidelines for further details (DSMP).
8
INTERVENTION DISCONTINUATION 
Early study termination will occur in the event of any unanticipated serious adverse event 
determined to be possibly, probably or definitely related to study procedures, failure to 
recruit at least 50% of the projected number of subjects within 4 months, or failure to retain 
at least 75% of study subjects to the conclusion of the protocol.
Subjects may withdraw voluntarily from participation in the study at any time and for any 
reason. If the participant is acutely ill, is in the hospital, or has a temporary condition that 
interferes with walking (e.g. ankle sprain), we will attempt to complete the assessment at 
another time. We will follow-up with participants who dropped out of the study to determine 
both their mobility status and reasons for withdrawal. We will use intention to treat (ITT) 
analysis, which includes all randomized participants in the groups assigned, regardless of 
adherence with entry criteria, whether motor imagery was received, and subsequent 
withdrawal or deviation from the protocol. ITT analysis is pragmatic because it admits 
noncompliance and protocol deviations, and gives an unbiased estimate of the intervention 
effect. Handling missing data is a major issue in ITT, and is dealt with by imputation or 
sensitivity analysis. Our statistician, Dr. Wang, is very experienced in these methods. 
A rich set of telephone-based information will be collected even for those subjects who may 
drop out. We will utilize this auxiliary information to assess the MAR assumption and 
combine it into the main model through joint modeling and multiple imputation approaches.
The research team will adjudicate events such as mobility disability in subjects who drop out 
based on medical interviews, contact interviews, and home assessments as required. For each 
study assessment, we will allow a 4-week window for completion.
9
STATISTICAL CONSIDERATIONS 
9.1
General Design Issues 
Our goal in this preliminary single-blind RCT is to determine the efficacy of motor imagery 
for improving gait and cognition in older adults. Baseline distribution of covariates will be 
compared to assess adequacy of randomization to produce comparable groups of participants 
using appropriate graphical procedures and summary statistics.
9.1.1. Primary outcome
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Gait speed was recommended to FDA as the preferred outcome for RCTs (39) because of its 
good validity, reliability, sensitivity to change, and predictive validity for multiple adverse 
outcomes.(39) We have reported that gait speed highly correlates with mobility related 
activities in our community.(40)
Reliability: We have reported excellent test-retest reliability of gait speed on GAITRite 
(Kappa >0.9).(41) Gait speed correlates highly with complaints of mobility limitations, falls 
and dementia in our studies.(41, 42) 
Practice effects: Gait speed improved only by <2% when tested twice 8 weeks apart in 
controls in our pilot study suggesting that longer intervals between gait assessments may 
help minimize practice effects.
Walking while talking test (WWT) is a novel ecologically valid mobility measure developed 
by our group.(43, 44) Our studies establish the incremental validity of WWT speed over 
NPW speed for predicting adverse outcomes such as falls, frailty and disability.(44) Other 
investigators have shown that training older adults on WWT like tasks translates into 
clinically relevant outcomes such as reduced falls, better balance, or improved function.(45) 
Hence, establishing the efficacy of motor imagery on our co-primary outcome of WWT 
speed alone could be of high clinical impact and relevance (irrespective of its effect on NPW 
speed).
Reliability: We reported good inter-rater reliability (r = 0.602) on a previous WWT 
version.(43) In 31 EAS subjects, we had excellent test-retest (r = 0.935) and inter-rater 
reliability (r = 0.918) for WWT speed.
9.1.2.
Secondary and Tertiary outcomes. 
Cognitive performance during the WWT – number of correct letters generated during WWT 
will be the main cognitive outcome. Additional cognitive/executive function tasks, including 
the WAIS-III Letter Number Sequencing Test (46), Stroop Color and Word Test (47), Trail 
Making Test (48) and Flanker Interference Task (49) will also be administered to determine 
if there are any far-transfer effects of our imagined gait intervention, and to carefully identify 
appropriate outcome measures for upcoming studies. Improved performance on the Stroop 
test following motor imagery training has been shown in individuals with Parkinson’s disease 
(13), and we have previously shown improved performance on the Letter Number 
Sequencing Task in cognitively-healthy older adults following a cognitive intervention (50). 
Additional neuropsychological measures of processing speed, language, and memory will 
also be examined (see ee Clinicaltrials.gov-NCT02762604 for a comprehensive list). 
Change in blood-oxygen-level-dependent (BOLD) signal will be examined during single 
(imagined walking) and dual task (imagined walking-while-talking) walking conditions. 
Changes in BOLD signal has been shown following physical and cognitive interventions in 
the past (51-53).  
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Additional variables/potential covariates will be recorded and carefully examined for 
potential inclusion as covariates or outcome measures in upcoming full-scale RCT, including 
stride length (cm), double support time (s), cadence (steps/min), swing time (s), stance time, 
stride length variability (SD), swing time variability (SD), the Geriatric Depression Scale 
(54), Medical Illnesses and Medication questionnaires (26, 55), Cognitive and Physical 
leisure activity questionnaire (56-58), Falls (59), Obesity (assessed with weight, waist 
circumference, and BMI (kg/m2)), Vision (Snellen’s chart), Disability (7 ADLs using the 
scale developed by Gill and colleagues (60, 61), IADL (62, 63), Blood pressure 
(Sitting/Standing), Gray Matter Volume/Atrophy (T1-Weighted structural images) White 
Matter Integrity (Diffusion Tensor Imaging; DTI) and White Matter Hyper intensities (Fluid-
Attenuated Inversion Recovery; FLAIR).    
9.2
Sample Size and Randomization
The primary hypothesis examines change in gait speed (during NPW and WWT conditions). 
Setting an alpha level of .05, power of .80 and a medium effect size of defined as f =.25, the 
necessary sample size for detecting an interaction between time of test (pre and post), trial 
type (W or WWT) and imagery condition (Imagined gait or AC)  is n = 34. Thus, our study 
completion goal of n = 48 (58 enrolled; 48 completed) is sufficient to detect our effects of 
interest and account for the 18% attrition rate expected during the study period (as observed 
in our previous studies (64)). 
To detect a BOLD signal change at the individual subject level (i.e. first-level time-series 
modeling using SPM) at p < 0.001, a percent signal change of 0.34% is required using a 
published method and estimate of noise at a magnet strength of 3.0 Tesla (65). Based on this 
estimate, to detect a difference in contrast values between groups (i.e. second level analyses 
using SPM) at p < 0.001 and a power of at least .80, where the mean of one group's signal 
change is 50% of the other, 16 subjects per group are required. Thus, our study completion 
goal of n = 48 (24 in each condition) is sufficient to detect a main effect of imagery condition 
(imagined gait vs. AC) and leave room for the detection of interactions
9.2.1. Treatment Assignment Procedures
Group assignment randomization will be generated by Dr. Wang using sequential study 
numbers so that the assistant who enrolls the participants will be blinded to randomization 
assignment of the next participant until assigned. Dr. Wang will not be involved with 
subject testing or interventions.
Given the nature of our interventions, double-blinding both subjects and testers will not 
be feasible. But we will include a number of methods (besides randomization) to reduce 
bias. 
•
Selection bias will be reduced by concealing treatment allocation until the subject 
is entered into trial. 
•
Primary outcome is an objective endpoint (gait speed) and not subjective mobility 
complaints.  
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•
Motor imagery and visual imagery interventions will be done at non-overlapping 
times.
•
Participants and study staff will be instructed not to disclose group assignment or 
details of interventions. 
9.3
Interim analyses and Stopping Rules
No interim analysis is planned for this pilot intervention of 48 volunteers. Early study 
termination will occur in the event of any unanticipated serious adverse event determined to 
be possibly, probably or definitely related to study procedures, failure to recruit at least 50% 
of the projected number of subjects within 4 months, or failure to retain at least 75% of study 
subjects to the conclusion of the protocol
9.4
Data Analyses
9.4.1
Primary outcome. 
To examine gait speed during W and WWT we will use repeated-measures analyses that 
include time of test (pre and post), and trial type (W or WWT) as within subjects factors, and 
imagery condition (imagined gait or AC) as the between-subjects factor. Consideration of 
these analyses will focus on the three-way interaction between time of test, trial type, and 
imagery condition. 
9.4.2. Secondary and tertiary outcomes. 
Similar repeated-measures analyses will be used for our secondary outcomes 
measures/additional EF measures:  Trail Making Test, the Letter Number Sequencing Test, 
the Stroop Color and Word Test, and the Flanker Interference Task. These measures include 
the time to complete Trails B corrected for Trails A from the Trail Making Test (Trails B-A), 
the raw score from the letter-number sequencing task WAIS-III, the raw response time to 
Color-Word (incongruent) trials corrected for Color (congruent) trials from the Stroop Color 
and Word Test (i.e., Stroop Interference) and the flanker interference response time measure 
(incongruent-congruent trials) from the Flankers interference task. Although three of these 
four measures are difference scores, our analyses will be completed on raw scores in order 
maximize power. More specifically, for these measures we will use repeated-measures 
analyses that included time of test (pre and post) and trial type as within subjects factors, and 
imagery condition (imagined gait or AC) as the between-subjects factor. Trial type for the 
Trail Making Test will be Trails A and Trails B. Trial Type for the Stroop Color and Word 
Test will be congruent trials and incongruent trials. Finally, trial type for the Flanker task will 
be congruous and incongruous trials. Consideration of these analyses will focus on the three-
way interaction between time of test, trial type, and condition. Analyses will focus on the 
primary outcome variables during training and to the end of training period.
All behavioral analyses will be corrected for multiple comparisons using the Bonferroni 
correction. 
We will use a whole-brain multivariate Ordinal Trend Covariance Analysis (OrT-CVA) to 
analyze the BOLD signal during imagined walking and walking while talking (66, 67). This 
is because we are interested in determining how the use of the entire locomotion and executive 
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function systems change as a function of our imagined gait versus the active control condition. 
This is also because changes in neural activation are often masked by between-subject 
variability, an issue that is particularly important to consider in aging populations (68, 69). 
Our multivariate analyses will be performed with software developed by my co-mentor in 
advanced neuroimaging analysis, Dr. Habeck: http://www.nitrc.org/projects/gcva_pca. OrT-
CVA will be used to identify covariance patterns in the fMRI signal as a function of trial type 
(iT, iW and iWWT) at each study visit (pre and post-intervention) for each imagery condition 
(imagined gait or AC). OrT-CVA is similar to other covariance analyses such as partial least 
squares (70, 71) in that it employs a principal components analysis (PCA) to the data matrix 
that is then transformed to a matrix of the experimental design. Linear regression is then 
applied to detect a covariance pattern, or ordinal trend, in the fMRI signal as a function of task 
conditions that is based on a linear combination of a small set of principal components. An 
ordinal trend is a monotonic change in pattern expression as a function of task conditions, in 
this case as a function of trial type (iW, iT and iWWT). The expression of an ordinal trend is 
quantified in terms of a participant-specific expression score that is derived by projecting the 
covariance pattern onto a participant’s scan for each task condition. These participant-specific 
(or pattern) expression scores can also be used for further analysis (e.g. to correlate with actual 
WWT performance). Note that the proposed multivariate analyses of fMRI data involve data 
reduction and therefore does not involve multiple comparisons.
Age, sex and education will be covariates in all analyses. Given that is a pilot RCT on a fairly 
small sample of participants, it is not statistically feasible to control for more than the basic 
covariates listed above. Additional variables/potential covariates will be recorded and 
carefully examined for potential inclusion as covariates or outcome measures in upcoming 
full-scale RCT, including stride length (cm), double support time (s), cadence (steps/min), 
swing time (s), stance time, stride length variability (SD), swing time variability (SD), the 
Geriatric Depression Scale (54), Medical Illnesses and Medication questionnaires (26, 55), 
Cognitive and Physical leisure activity questionnaire (56-58), Falls (59), Smoking and alcohol 
consumption questionnaires, Obesity (assessed with weight, waist circumference, and BMI 
(kg/m2)), Vision (Snellen’s chart), Disability (7 ADLs using the scale developed by Gill and 
colleagues (60, 61), IADL (62, 63), Blood pressure (Sitting/Standing), Gray Matter 
Volume/Atrophy (T1-Weighted structural images) White Matter Integrity (Diffusion Tensor 
Imaging; DTI) and White Matter Hyper intensities (Fluid-Attenuated Inversion Recovery; 
FLAIR).
10
DATA COLLECTION AND QUALITY ASSURANCE
10.1 Data Collection Forms
Confidentiality will be preserved by use of ID code numbers for identification. ID and name 
associations will be password protected in an encrypted master file to which only the PIs and 
statistician will have access. Participant data, including computer data disks, will be kept in a 
locked room. Identifying information about a subject will not be used during the discussion or 
presentation of any research data.  To ensure confidentiality and anonymity during the study, each 
subject will be assigned a confidential study number. Access to the subject study identification 
codes or other information will be restricted to the PIs, co-investigators, and study staff, and upon 
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written request, to the IRB or other regulatory agencies, or by written request of the subject, 
released to others. Paper records will be stored in locked file cabinets in the investigators’ offices, 
and all computers used for data management and analysis will be password-protected and located 
in secure offices.
10.2 Data Management 
Behavioral data will be entered, stored and maintained in a REDcap database (72). REDcap 
provides a secure web-based application for developing, and managing data bases, and is used by 
thousands of active institutional partners in more than one hundred countries. Our study site, Albert 
Einstein College of Medicine, provides on-site support for the development, upkeep, and 
maintenance of REDcap databases. Only trained RAs will be permitted to enter data in this 
database, and REDcap automatically records the date, time and the person who entered or changed 
data into a database. Neuroimaging data will be stored, maintained, processed and analyzed in a 
secure Linux server environment. 
Participant confidentiality will be maintained by assigning each subject a unique study ID upon 
entry to identify and link subject data. ID and name associations will be password protected and 
only the data manager, PI and primary mentor will have access. 
10.3 Quality Assurance 
10.3.1
Training
All study staff have taken the Safety Training Class-an online training venue that provides an 
overview of human subjects safety surveillance and reporting requirements in clinical 
research studies. The intent of the course is to help clinical study investigators and staff 
understand and implement NIA and regulatory requirements for safe, high quality clinical 
research. The topics covered include Good Clinical Practice (GCP), Human Subject 
Protections, Adverse Events and Unanticipated Problems, Safety Monitoring and Reporting 
Requirements, Safety Monitoring and Oversight: DSMBs and Safety Officers, Regulatory 
Requirements and Responsibilities of PIs, and Data and Safety Monitoring Plans. 
They have also all successfully completed the required CITI training courses.
10.3.2
Quality Control Committee
N/A
10.3.3
Metrics
We will train competent staff to conduct the interventions and assessments, ensure they 
understand the nature of the interventions, and understand adverse event reporting 
requirements. Trained clinical assistants, who will monitor the participant for any adverse 
events, will perform all assessments. The clinical assistant will stop the testing procedures if 
participants feel stressed or get embarrassed by their performance, and relay the information 
immediately to Drs. Blumen and Verghese. At least one member of the research team will be 
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present onsite during all testing and intervention sessions.  In addition, Drs. Blumen and 
Verghese will be available by pager and cellular telephone at all times to address any safety 
concerns or clinical issues. 
The PIs will monitor performance and safety issues on a day-to-day basis. In addition the 
DSMB will be responsible for the following which will ensure the quality, accuracy and 
efficiency of the study.
•
Review the research protocol, informed consent documents and plans for data safety and 
monitoring;
•
Recommend participant recruitment be initiated after receipt of a satisfactory protocol;
•
Evaluate the progress of the trial, including periodic assessments of data quality and 
timeliness, recruitment, accrual and retention, participant risk versus benefit, performance 
of the trial sites, and other factors that can affect study outcome;
•
Consider factors external to the study when relevant information becomes available, such 
as scientific or therapeutic developments that may have an impact on the safety of the 
participants or the ethics of the trial;
•
Review study performance, make recommendations and assist in the resolution of 
problems reported by the PIs;
•
Protect the safety of the study participants;
•
Report to NIA on the safety and progress of the trial;
•
Make recommendations to the NIA and the PIs concerning continuation, termination or 
other modifications of the trial based on the observed beneficial or adverse effects of the 
treatment under study;
•
Ensure the confidentiality of the study data and the results of monitoring; and,
•
Assist the NIA by commenting on any problems with study conduct, enrollment, sample 
size and/or data collection.
10.3.4
Protocol Deviations
Protocol deviations will be recorded and documented for each participant in the database 
calendar. All adverse event forms will be completed and reported as described above. 
All protocol and MOP changes and/or amendments will be recorded on an ongoing basis and 
reported to the IRB as well as documented on the cover page of this protocol.
10.3.5
Monitoring
All data collection in this clinical trial will be monitored to assure participant comfort, safety, 
and confidentiality. The clinical trial protocols, data collection instruments, participant 
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recruitment letters, and consent forms will be reviewed and approved by the IRB prior to 
study initiation. We will also provide an annual progress report to the IRB and NIH. The study 
coordinator will be responsible for preparing these reports. 
The DSMB will monitor participant safety, evaluate the progress of the study, to review 
procedures for maintaining the confidentiality of data, the quality of data collection, 
management, and analyses. The PI will monitor performance and safety issues on a day-to-
day basis. Both closed and open meetings of the DSMB will be held on a biannual basis. In 
addition the DSMB will meet more or less frequently as study progress dictates. 
If PIs become aware of issues that threaten the integrity of the trial or participant safety, they 
will alert the NIA representative to the DSMB who will consult with the DSMB Chair as to 
whether a special meeting or conference call of the DSMB should be held. 
The open session report will focus on patient accrual and demographics, data completeness, 
and other study performance measures. Only aggregate data will be presented during the open 
session (i.e., not segregated by treatment). The closed session report will divide study 
participants according to coded treatment assignment, comparing participant demographics 
and baseline characteristics, rates and reasons for treatment discontinuation and loss to follow-
up, and rates of serious adverse events. The PIs may prepare a report addressing concerns they 
anticipate the DSMB will have regarding the conduct of the study.
The data reports will include:
•
Cumulative accrual
•
Baseline characteristics, overall and by treatment group 
•
Summary of completeness and quality of data collection forms
•
Status of enrolled participants, overall and by treatment group 
•
Assessments of whether study personnel have followed eligibility criteria and other 
protocol requirements
•
Assessment of participant adherence, overall and by treatment group
•
Outcome rates, overall and by treatment group along with monitoring boundaries for 
efficacy and futility (if the planned interim analysis is due)
•
Listing of serious adverse events by participant ID number and a table of event-specific 
cumulative rates, overall and by treatment group
•
A summary description of all serious adverse events
11
PARTICIPANT RIGHTS AND CONFIDENTIALITY 
11.1 Institutional Review Board (IRB) Review
This protocol, the informed consent (Appendix I), all recruitment materials, assessments 
and scripts as well as any subsequent modifications to these documents will be reviewed 
by the IRB.  
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11.2 Informed Consent Forms
A signed consent form will be obtained from each participant (Appendix I). The consent 
form describes the purpose of the study, the procedures to be followed, and the risks and 
benefits of participation. A copy will be given to each participant and this fact will be 
documented in the participant’s record. 
11.3 Participant Confidentiality 
Any data, forms, reports, video recordings, and other records that leave the site will be 
identified only by a participant identification number (Participant ID) to maintain 
confidentiality.  All records will be kept in a locked file cabinet.  All computer entry and 
networking programs will be done using PIDs only. Information will not be released 
without written permission of the participant, except as necessary for monitoring by IRB 
and the NIA. 
11.4 Study Discontinuation 
The study may be discontinued at any time by the IRB and the NIA or other government 
agencies as part of their duties to ensure that research participants are protected. 
12
ETHICAL CONSIDERATIONS
Recruitment, enrollment, and participation of participants in this project are not limited by 
gender, skin color, racial/ethnic group, or economic status. We will monitor recruitment 
and retention patterns to ensure adequate representation of women and minorities.
13
COMMITTEES
N/A
14
PUBLICATION OF RESEARCH FINDINGS
Any presentation, abstract, or manuscript will be made available for review by the sponsor 
and the NIA prior to submission.
15
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16 SUPPLEMENTS/APPENDICES
I. Informed Consent Form
II. Adverse Event Log and Serious Adverse Event Form
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Appendix I-Informed Consent
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Appendix II-Adverse Event Log
IRB #: 2014-3633
PI: Helena Blumen
Subject 
ID#
Date of
Onset
Date
Resolved
Outcome
*
Serious-
ness**
Relation-
ship***
Unanticipated 
(Y/N)
Action with
Study
Treatment****
Reportable
to Sponsor 
(Y/N)
Date 
Sent 
to 
NIH 
& 
DSMB
Reportable
to IRB
(Y/N)
Date 
Sent to 
IRB
PI 
Initial
s and 
date
Event Description:
Event Description:
Event Description:
Event Description:
Event Description:
Event Description:
Key
*Outcome
1.
Resolved
2.
Resolved with sequelae
3.
Recovering
4.
Not 
Recovered/Not 
Resolved
5.
Fatal
6.
Unknown
**Seriousness
1.
Fatal
2.
Life-threatening
3.
Serious
4.
Not Serious
***Relationship
1.
Definite
2.
Possible
3.
Probable
4.
Unlikely
****Action 
with 
Study 
Treatment
1.
No Action
2.
Interrupted
3.
Discontinued
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017

Serious Adverse Event Report Form
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Version 1.1
Serious Adverse Event (SAE) Report Form
1. SAE Onset Date: [enter SAE onset date] (dd/mmm/yyyy)
2. SAE Stop Date: [enter SAE stop date] (dd/mmm/yyyy)
3. Location of serious adverse event (e.g. at study site or elsewhere):
[Enter location of SAE]
4. Was this an unexpected adverse event? 
 Yes
 No
5. Brief description of participant with no personal identifiers:
Sex:
 Female
 Male
Age: [Enter participant age]
6. Adverse Event Term(s):
[Enter adverse event terms]
7. Brief description of the nature of the serious adverse event (attach description if more space needed):
[Enter brief description of the nature of the SAE]
8. Category of the serious adverse event:
 death – date [Enter death date](dd/mmm/yyyy)
 congenital anomaly / birth defect
 life-threatening
 required intervention to prevent
 hospitalization - initial or prolonged
permanent impairment
 disability / incapacity
 other:[other category of SAE]
9. Intervention type (circle one):
Motor Imagery training
Visual Imagery training
Protocol Title: Motor Imagery: A Pilot Intervention for Improving Gait and Cognition in the Elderly. 
Protocol Number: 2014-3633
Pt_ID: [Enter participant id]
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017

Serious Adverse Event Report Form
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Version 1.1
10. Relationship of event to intervention:
 Unrelated (clearly not related to the intervention)
 Possible (may be related to intervention)
 Definite (clearly related to intervention)
11. Was study intervention discontinued due to event?
12. What medications or other steps were taken to treat serious adverse event? 
[Medications or other steps were taken to treat SAE]
13. List any relevant tests, laboratory data, history, including preexisting medical conditions
[List any relevant tests, lab data, history, including preexisting medical conditions]
14. Type of report:
 Initial
 Follow-up
 Final
Signature of Principal Investigator: [Signature of PI] Date: [sign date] (dd/mmm/yyyy)
 Yes
 No
IRB NUMBER: 2014-3633
IRB APPROVAL DATE: 06/16/2017