Social Dancing Intervention for Older Adults at High Risk of Alzheimer's Disease and Other Dementias: A Pilot Study.
Phase: NA
Conditions: Alzheimer Disease, Dementia, Cognitive Decline, Cognitive Impairment, Dementia, Alzheimer Type
Sponsor: Albert Einstein College of Medicine

MOTOR INTERVENTION FOR MEMORY ENHANCEMENT (MIME) 
 
 
Principal Investigators: 
Joe Verghese, MBBS (contact PI) & Helena Blumen, PhD 
1Departments of Neurology and Medicine, Albert Einstein College of Medicine, Bronx, NY. 
Supported by: 
The National Institute on Aging 
R21AG057586 
ClinicalTrials.gov Identifier: NCT03475316 
 
 
 
 
Version 1.2 
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1) Background/Significance:
Social dancing is a complex sensorimotor rhythmic activity integrating physical, cognitive and social elements 
with the potential to ameliorate a wide range of physical and cognitive impairments in older individuals at risk of 
Alzheimer’s disease (AD) and related dementias. We reported that social dancers had a 76% reduced risk of 
dementia compared to non-dancers.1 The few extant studies report that dancing stimulates multiple cognitive 
processes, including attention, processing speed, and executive function, but these discoveries were made in 
small samples, lacking control conditions, and did not investigate the underlying biological mechanisms.2-6 
Executive function (EF) is an umbrella term for the management of cognitive processes, including working 
memory, reasoning, task flexibility, and problem solving that are central to planning, goal-directed action, and 
coordination of daily activities. Impairment of EF and related processes such as processing speed and attention 
is seen in normal aging as well as early in dementia, and is associated with difficulty in performing daily activities 
and increased risk of adverse events such as falls. Encouragingly, aerobic exercise is reported to enhance 
cognition, especially EF.7, 8 Cognitively impaired seniors fall more,9 and have higher prevalence and severity of 
balance and gait problems than cognitively intact fallers.10-12 Given social dancing’s multimodal cognitive and 
physical benefits; it may help maintain mobility and reduce falls in individuals at risk for dementia. In support, we 
reported that older social dancers had better balance and gait than non-dancers.13  
We propose a 6-month pilot single blind, randomized clinical trial (RCT) comparing social dancing 
(ballroom dancing) versus active control (walking) in 32 older adults at high risk of dementia. Our overall 
hypothesis is that social dancing in cognitively vulnerable seniors will induce neuroplasticity that will enhance 
cognitive processes and improving everyday behaviors. Our objective for this pilot trial is to examine feasibility 
as well as obtain preliminary data on intervention effects (trajectory and asymptote) on EF to design a full-scale 
RO1.
Aim 1: Obtain preliminary data regarding feasibility and effects on cognition of social dancing in seniors 
at risk for dementia. Dementia at-risk status is defined as cognition lower than expected for age (see 2.B for 
justification and criteria); similar approach was used in recent lifestyle interventions trials with cognitive 
outcomes.14-17  While preliminary studies support a possible cognitive benefit of dancing, most studies have not 
targeted older individuals at high risk for dementia, a highly prevalent group with faster rates of cognitive decline. 
We will, hence, establish feasibility of conducting social dancing intervention in seniors at risk for dementia (see 
Table 1 for feasibility parameters). 
We will track changes in a composite EF score derived from a battery of standardized (Digit symbol 
substitution test: DSST),18, computerized (Flanker test),19, 20 and cognitive-motor (Walking While Talking: WWT) 
tests to capture various facets of this broad domain. Composite cognitive scores were used to define outcomes 
in many recent RCTs.21-23 We will administer tests at baseline, month 2, month 4, month 6 (end of intervention) 
and month 9 (3 months post-intervention) to determine trajectory (as well as any asymptote) on improvement 
in both groups that will help plan optimal duration for our full-scale RO1. These highly reliable EF tests were 
used to show exercise effects on cognition,8, 24-27 and predict cognitive (dementia) and non-cognitive outcomes 
(falls).28-31 The composite EF score helps overcome limitations of single EF tests.21-23 
Aim 2: Explore functional and structural neuroplasticity for cognitive benefits of social dancing in 
seniors at risk for dementia. We will explore neuroplasticity in functional activation/deactivation and structural 
connectivity patterns as a function of social dancing (pre-post intervention). We will use functional Magnetic 
Resonance Imaging (fMRI) to investigate neuroplasticity in functional activation/deactivation patterns with our 
validated ‘imagined WWT’ task32- as well as with DSST and Flanker tests, which are responsive to physical 
interventions.25 We predict that compared to walking, dancing will result in greater intervention-related changes 
in functional activation of supplementary motor, anterior cingulate and prefrontal regions during imagined WWT, 
DSST and Flanker tests. 
To investigate neuroplasticity in structural connectivity patterns, we will use diffusion-weighted 
imaging, which are responsive to social dancing and physical interventions.33, 34 We predict that compared to 
walking, dancing will result in greater intervention-related changes in structural connectivity patterns, including 
fornix and cingulum.  
Social dancing appeals to older adults, has intrinsic value, is enjoyable, and has high potential for 
sustainability. This R21 proposal is novel and high risk, but will provide the evidence base to develop a 
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definitive full-scale RCT to support or refute prescription of social dancing to prevent cognitive decline in older 
adults at high risk of AD and related dementias.
2) Study Design 
Overview and Design. We propose a pilot single blind RCT of social dancing versus walking in 32 dementia 
at-risk seniors (16/group). For Aim 1, outcome is change in EF composite score measured with a 
comprehensive battery of conventional (DSST), computerized (Flanker test) and cognitive-motor (WWT) EF 
tests assessed at baseline, month 2, month 4, month 6 (immediate post-intervention), and 3 months post-
intervention to derive trajectories to inform design of future R01. Feasibility is assessed through metrics 
described in Table 1. For Aim 2, outcome is neuroplasticity measured using our validated fMRI iWWT protocol, 
DSST and Flanker Tests, and white matter integrity.
a) RECRUITMENT AND SCREENING: We will enroll 32 dementia at-risk seniors over 2 years. Our 
sample size is not based on demonstrating clinical efficacy but to obtain preliminary data and 
feasibility to plan our RO1. We will contact a random sample of individuals age 65 and over identified 
from local population lists as well as from the large clinical population in our health system. Both 
sources were used to recruit ~3000 participants for our aging studies.35-37 A letter explaining our study 
is followed by a telephone call. Those expressing interest on the telephone are screened with Memory 
Impairment screen (MIS)38 and AD-839 to establish dementia-risk status. Potential recruits will be invited 
for an in-person visit where final eligibility is determined. Written consent and screening is at our 
research center. An independent DSMB will be constituted prior to the start of the study.
b) ELIGIBILITY CRITERIA. Our target population is dementia at-risk seniors. Patients will be evaluated by 
research assistants followed by the study clinician to assess eligibility for the trial. 
i)
Inclusion criteria: 1) Age 65 and older. 2) ‘At-risk for dementia’ status defined as meeting cutscores 
on either MIS (≤ 6) or AD-8 (≥1) tests. The MIS is a 4-item dementia screener developed in our 
Bronx population.38, 40 MIS accounts for various educational levels.41-44 The AD-8 is a 2-minute 
screener with high validity for detecting dementia.39, 45 AD-8 is less educationally biased as it does 
not test patients on acquired learning. AD-8 is culturally neutral as it focuses on changes in basic 
activities in which everyone engages. Both tests correlate highly with dementia pathology.46, 47 We 
used these 2 screeners to enroll 3000 participants in 3 NIH funded studies.38, 48, 49  We decided 
against MCI as a criterion, as its prevalence is low (<12% in our community-based cohort50); limiting 
generalizability. We examined validity of our ‘dementia at-risk’ definition in 543 older adults in the 
Einstein Aging study;48 176 met dementia at-risk criteria (prevalence 32%). Over a mean follow-up 
of 1.5 years, ‘dementia at-risk’ status predicted incident cognitive impairment (any of MCI, Motoric 
cognitive risk syndrome (MCR)51, 52 or dementia) (HR adjusted for age, sex, education and illnesses 
2.0, 95%CI 1.1-3.8).  Hence, our definition captures a high-risk yet highly prevalent group. 3) 
Sedentary: exercises less than the CDC recommended level of 150 min moderate intensity 
activity/week.53 4). Agree to neuroimaging: more efficient to enroll those who also meet imaging 
criteria for this pilot. We recruited >100 participants in the last 2 years for various imaging studies. 
ii)
Exclusion criteria: 1) Active medical or major psychiatric illnesses. 2) 
Musculoskeletal/cardiovascular mobility limitations. 3) Competitive dance or regular social dance 
(>1/month). As seniors may occasionally dance at social events (but not at dose for cognitive 
benefits), excluding all seniors who ever danced is not practical. 4) Presence of dementia106 
(telephone or in-house evaluation). 5) Standard imaging exclusions.  It will not be feasible to obtain 
MRI or other biomarkers to screen and enroll participants. However, the pre-intervention MRI for 
Aim 2 will allow us to stratify the at-risk group into those with or without brain pathology (e.g. 
hippocampal atrophy54) for exploratory analyses. 
c)
RANDOMIZATION. Eligible participants are randomized for interventions at initial visit, stratified by 
gender and age (< or >80 years). Equal number of men and women will be enrolled. Group assignment 
is generated by Dr. Wang, who is not involved in subject testing or interventions. She will generate an 
encrypted file with the randomization order to assign participants to the study arms. She will be the only 
one with access to the list.  To avoid attrition following enrollment, we will not wait to recruit all 
participants to start the interventions but will have rolling admission into the dance and walking classes. 
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i)
Social Dance (intervention arm): 90-min dance sessions twice weekly for 6-months. The session 
includes warm-up, dance and cool down. The program includes Foxtrot, Waltz, and Latin dances. 
The choice of multiple dances is pragmatic since it mirrors the choice offered in senior centers and 
avoids tedium of only doing one dance form. Intensity will not be manipulated to mimic exercise 
training as in aerobic dance classes. Dance instructors are experienced in teaching seniors (see 
LOS from USA Dance). Progression to new dances will be gradual and take into account balance, 
cardiac and cognitive demands. Methodological structure is the same for all sessions. The 
instructor will demonstrate the dance sequence. Participants warm up with gentle stretches. The 
instructor will repeat dance sequence several times and the participants will try to reproduce it along 
with the instructor, until sequence is learned. When participants execute the dance sequence 
satisfactorily, they will reproduce it along with the music.
(a) Duration (6 months), frequency (2/wk) and intensity based on earlier dance studies and 
pragmatic considerations. A review of dance interventions for various health outcomes 
(including cognition) concluded that dance programs should provide a minimum of one 45-
minute session per week for 6 weeks (lower than our study).55 The dose of exercise in both 
dancing and walking arms is higher than the CDC recommended exercise dose.53 
(b) Pairing at dances is at random and the instructor will ensure participants rotate partners.
(c) Performance monitoring: Intensity measurement via accelerometers and cardiac 
monitoring during dance lessons. 
(d) Dancing integrates physical, cognitive and social elements. Our interventions may also 
improve mood, self-esteem, and self-efficacy.56, 57 We will measure each of these 
components. However, a detailed mechanistic examination of which dance components 
contribute to cognitive benefits is beyond the scope of this pilot study, and will be done in 
our future RO1. Randomization is also a powerful tool to address biases due to 
confounders.
ii)
Walking (active control): We completed a pilot walking study in frail seniors supporting 
feasibility.58 Participants meet twice weekly for 6-months matching frequency and intensity in the 
dance group. Recent reviews report minimal to no cognitive benefits from exercise programs in 
cognitively impaired seniors.26, 59-61 Walking exercises was reported in another review to show 
modest EF benefits in healthy but not cognitively impaired seniors (our focus).62  Dr. Verghese was 
part of the LIFE study that reported that moderate-intensity physical activity program (walking) in 
sedentary seniors did not improve global or domain-specific cognitive function (including EF) 
compared to those in a health education program.63  A recent review by the National Academy of 
Medicine concluded that the evidence was encouraging but inconclusive regarding cognitive 
benefits of exercise, and further research was required.64
(a) Procedure: The protocol is based on American College of Sports Medicine65 and American 
Heart Association66 recommendations for seniors. Additional details are in our published 
report.58 Briefly, each session starts with 5-10 minutes of warm-up walking at comfortable 
speed.  Speed is gradually increased to the level at which participants felt it is ‘somewhat 
hard’ (12-14 Borg scale67, 68) for two 35 minute sessions with breaks in between followed by 
5-10 minute cool down period (total 90 min to match dance group). Training interval is 
gradually increased over the first 2 weeks. 
(b) Environment: The indoor environment that is less subject to weather and other barriers 
when walking outdoors. 
(c) Social interactions: To match the social aspect of dance, treadmills will be arranged in 
clusters. The proportion of men to women is the same as in the dance group. Music will be 
played during treadmill sessions to minimize variability.
d) OUTCOMES Aim 1 (Cognition): As EF includes multiple cognitive processes; a single test is not 
sufficient. We will examine a composite EF score by summing standardized scores on the 3 tests.  
Composite cognitive scores were used in many RCTs.21-23 We will also compare trajectories in 
individual tests to gain insights into study design of our full-scale RO1. Study outcomes will be 
assessed at baseline, month 2, month 4, post-intervention (end of month 6), and 3 months post-
intervention (month 9). 
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i)
Digit Symbol Substitution test (DSST) is a timed test that assesses speed of processing, visuo-
spatial attention and EF. DSST predicts cognitive (dementia) and non-cognitive outcomes (falls). 
DSST is amenable to exercise.69 
ii)
Flanker Test is in the NIH toolbox.19, 20 It measures attention and inhibitory control. The Flanker test 
was used to demonstrate exercise effects on EF.8, 70 
iii) Walking While Talking test (WWT) is an EF-dependent everyday behavior measure developed by 
our group.29, 30  Dual-tasking assessed by WWT is a defined facet of EF,36, 71 and associated with 
increased prefrontal activation.72 Participants walk on an instrumented walkway for 2 trials reciting 
alternate letters of the alphabet.73 See our published papers for WWT procedures.28-30, 72-74 WWT 
has excellent test-retest and inter-rater reliability.28-30 
Blinding: While double-blinding both subjects and testers is not feasible, the following steps 
(besides randomization) are included: A. Selection bias reduced by concealing treatment allocation 
until subject enrolled.75 B. Outcome is an objective endpoint and not subjective reports.75 C. Dance 
and walking groups meet non-overlapping times. D.  Each aspect of the RCT is supervised 
independently: interventions (Ayers), assessments (Verghese) and imaging (Blumen). E. 
Participants/staff instructed not to disclose group assignment or interventions. 
Learning effects: We will utilize 4 complementary approaches to attenuate practice effects76: (1) 
Practice pre-baseline to reduce task familiarity effects; (2) Item-specific driven improvements 
minimized by using tasks with multiple similar items and standardized encoding; (3) We developed 
alternate forms for the WWT task,74 and alternate forms of the DSST are available; and (4) use of 
control group.
e) OUTCOME Aim 1 (Feasibility): Metrics below will identify barriers and refine design of our full scale 
RCT.77
Metric
Measurement
Comments
Recruitment
Analyze recruitment sources by PI. 
Monitor to improve recruitment rates and identify 
barriers.
Implementation
Proportion completed successfully. 
Observe all phases to find 
bottlenecks
Compare completion rates by education. Testers 
feedback on non-completion and other barriers to 
develop solutions.
Retention
Retention rates to be reported. 
20-25% attrition common in high-
risk samples.
Dancing program implemented in frailty and 
dementia.6, 15, 78-82  Make-up sessions provided. 
Transportation and snacks will be provided. 
Dose/frequency accounted in analyses. 
Compensation at $10/session consistent with IRB 
guidelines, and has been reported to promote 
adherence in exercise programs.83
Safety
Staff monitoring/DSMB oversight
DSMB and safety procedures 
Practicality
PI, staff and subject observations 
Extent to which intervention can be done with available 
resources
Acceptability
Post-study interviews of 
participants
Help refine RO design and enhance generalizability
Reporting
Report pilot study design and 
results
CONSORT guidelines will be followed: See ref84 for 
details.
f)
OUTCOME Aim 2 (Neuroplasticity): Encouragingly, pilot dance intervention trials have shown 
neuroplasticity with similar or smaller samples (12 to 48) over 6-months or less,3, 85-89 including the 
FAST study34. Our primary neuroimaging measure is task-based fMRI because functional brain 
changes are a more sensitive biomarker of AD than gray matter volume. Our exploratory neuroimaging 
measure is DTI because it has been shown to be sensitive to aerobic exercise33 and social dancing 
intervention.34, 90  Furthermore, functional and structural changes may occur before the emergence of 
cognitive symptoms in dementia.91-95
i)
Task-Based fMRI (Primary): We will examine functional activation/deactivation changes pre-post 
intervention in both groups during an imagined WWT (iWWT) protocol developed by our group.32  
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The iWWT is strongly correlated with actual WWT performance, and engages a distributed network 
of brain regions, including cerebellar, precuneus, supplementary motor and other prefrontal 
regions.32 The iWWT protocol involves 5 repeated blocks of imagined walking (iW), imagined talking 
(iT), and iWWT, and takes 12 minutes to administer. We will also examine functional 
activation/deactivation changes during DSST and Flanker tests. We will use a DSST task adapted 
for use in an fMRI environment and validated in older adults.96 This task takes about 10 minutes 
and has 2 practice and 5 testing blocks, with 18 items each (total 95 test items). We will also use a 
Flanker task optimized for fMRI environment, with a 4-minute practice block and three 4-minute test 
blocks for a total of 120 test items (60 congruent, 60 incongruent) presented with jittered inter-
stimulus intervals (4-8 sec).97  We predict that dance will increase activation in supplementary 
motor, anterior cingulate and other prefrontal cortex regions during the iWWT, DSST and Flanker 
tasks to a greater extent than walking. We expect treadmill training to increase activation in the 
somatosensory cortex and the cerebellum. Jovancevic et al noted differences in activation in 
response to DSST on fMRI in 5 women (mean age 55) in the left middle frontal gyrus, right inferior 
parietal lobule, and left angular gyrus following a 6-week video dance program.98
ii)
Diffusion-Weighted Imaging (exploratory). We propose to examine pre-post changes in 
structural connectivity as a function of social dancing.  Structural changes in white matter integrity 
have been observed following physical and social dancing interventions.34 Based on these initial 
findings, we propose to monitor structural changes in white matter integrity (fractional anisotropy) 
using Tracts Constrained by Underlying Anatomy (TRACULA).99 We expect that dance will change 
white matter integrity in fornix, cingulum and over frontal integrity to a greater extent than walking. 
g) Other measures: We will collect other measures to explore the broader impact of dancing. Given R21 
space limits, these measures are summarized in Table 1. We have administered 3-hour test batteries to 
over 3000 participants in our other aging studies with minimal attrition. 
3) DATA AND SAFETY MONITORING PLAN:
1.0 Particpants Safety
1.1 Potential Risks and Benefits for Participants
Potential Risks: We do not expect any serious adverse events during these non-invasive tests and training 
programs of attention and executive function. Answering health questionnaires and mental state examinations 
involve minimal psychological, social, or other risks. 
Dance classes will be taught by certified dance instructors (with experience teaching seniors) at varying levels 
of complexity and the progression during the intervention period will be gradual. Progression to new dances 
will take into account the balance challenge, cardiovascular demand, degree of flexibility, coordination and 
cognitive demand. The instructor will ensure that the programs will not be manipulated to mimic exercise 
training as in aerobic dance classes. 
The treadmill training walking intervention protocol will be based on recommendations of the American College 
of Sports Medicine (ACSM)106 and American Heart Association (AHA) for older adults. A gradual approach will 
be applied to increase exercise intensity in participants with a low baseline level of physical activity and who 
Table 1. Summary of secondary outcomes, covariates and process measures 
Domains
Tests and procedures (refs)
Description (0,2,4,6, 9 months)
Time
Clinical
Study clinician evaluation35, 100 of 
neurological and musculoskeletal 
systems including gait
Standardized examination and CDR rating.
Clinicians Global Impression of Change101, 102 
30 m
Cognitive
Neuropsychological battery103
Test of multiple cognitive domains.103 
60 m
CHAMPS104
Lifestyle changes baseline and post-
intervention
15 m
Gait variables
GAITRite
10 m
Balance
Unipedal stance, trunk sway (covariate)
5 m
ADL scales
Monitor changes in function
5 m
Mood
Geriatric depression scale105
Depressive symptoms (covariate)
5 m
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may be unfamiliar with treadmill walking. Pulse and blood pressure will be assessed before and after each 
session to assure that the values are not deviated by 10 or more from the values of initial assessment for pulse 
and systolic blood pressure. During exercise, participants are monitored with the subjective Borg scale68 every 
5 minutes and heart rate is tracked by a physical therapist. Participants are encouraged to increase the training 
velocity if the subjective rating of exercise intensity is low (fairly light, Borg score <12). The treadmill speed will 
be reduced or exercise aborted if there are any untoward symptoms such as cardiovascular symptoms or 
excessive fatigue. Heart rate will be measured during the break between training periods and the second 
period will only be initiated after the value is below the 70% of estimated maximum heart rate.106 Similar 
procedures will also be followed in the dance intervention group.
Potential Benefits: Our previous experience, the non-invasive nature of most proposed procedures, the 
widespread prevalence of dance and exercise programs in the community, the general acceptance by 
practicing physicians of the procedures to be used, and the close supervision and monitoring of the subjects all 
minimizes the potential risks. Both dancing and walking may improve physical fitness, and involve minimal 
risks to the participant. Early diagnosis and treatment of disorders discovered as a result of screening done in 
these studies may impact beneficially on their health. In addition, understanding of the role of physical, mental, 
and social activities in ameliorating age-related cognitive decline could provide important insights into the aging 
process and age-related diseases that could ultimately have a positive impact on the length and quality of life 
for study subjects.  
1.2 Adverse Event and Serious Adverse Event Collection and Reporting
Adverse Events (AEs): Any untoward or unfavorable medical occurrence in a human subject, including any 
abnormal sign (for example, abnormal physical exam or laboratory finding), 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. AEs encompass both physical and/or psychological harms.
Serious Adverse Events (SAEs): An adverse event that meets any of the following criteria:
•
Results in death 
•
Is life threatening, or places the participant at immediate risk of death from the event as it occurred 
•
Requires prolonged hospitalization 
•
Causes persistent or significant disability or incapacity 
•
Is another condition which investigators judge to represent significant hazards
Unanticipated Problem: Any event, deviation, or problem, that meets ALL of the following criteria:
a.
Unexpected (see Expectedness definitions below) in terms of nature, severity, or frequency given (a) 
the research procedures that are described in the IRB-approved research protocol and informed 
consent document; and (b) the characteristics of the subject population being studied;
b.
Related or possibly related (see Relatedness definitions below) to participation in the research; and
c.
Suggests that the research places subjects or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized.
Adverse Events versus Unanticipated Problems: 
•
The vast majority of adverse events occurring in human subjects are not unanticipated problems.
•
A small proportion of adverse events are unanticipated problems.
•
Unanticipated problems include other incidents, experiences, and outcomes that are not adverse 
events.
Reporting: All AEs are collected on an Adverse Event Form in electronic format and recorded in the RedCap 
database. All AEs experienced by the participant from the start of intervention through the end of the study 
intervention period (6-months) will be reported to the Safety Officer (SO) and NIA in Safety Reports sent twice 
a year.
Unanticipated Problems Reporting: Unanticipated problems will be reported within 48 hours to NIA Program 
Officer and to the SO and will include a corrective plan and measures to prevent reoccurrence. 
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SAE Reporting: When SAEs occur that are unanticipated (i.e., events other than those described in the 
protocol, consent form and DSMP), and that are related to the intervention, they will be reported to NIA 
Program Officer and to the SO within 48 hours of study’s knowledge of the SAE. The expedited report will be 
followed by a detailed, written SAE report as soon as possible. Follow up information may be required and 
asked for by the SO or the NIA.
Any anticipated AEs and SAEs will be reported in the bi-annual reports to the SO and NIA Program Officer.
Relatedness:
The potential event relationship to the study intervention and/or participation is assessed by the site 
investigator. The comprehensive scale to categorize an event is listed below:

Definitely Related:  The AE is clearly related to the investigational procedure – i.e. an event that 
follows a reasonable temporal sequence from administration of the study intervention, follows a 
known or expected response pattern to the suspected intervention, that is confirmed by 
improvement on stopping and reappearance of the event on repeated exposure and that could not 
be reasonably explained by the known characteristics of the subject’s clinical state.

Possibly Related:  An AE that follows a reasonable temporal sequence from administration of the 
study intervention follows a known or expected response pattern to the suspected intervention, but 
that could readily have been produced by a number of other factors.

Not Related:  The AE is clearly not related to the investigational procedure - i.e. another cause of 
the event is most plausible; and/or a clinically plausible temporal sequence is inconsistent with the 
onset of the event and the study intervention and/or a causal relationship is considered biologically 
implausible. 
Expectedness:
AEs must be assessed as to whether they were expected to occur or unexpected, meaning not anticipated 
based on current knowledge found in the protocol and the consent form. Categories are:

Unexpected: The nature or severity of the event is not consistent with information about the 
condition under study or intervention in the protocol or consent form. 

Expected: The event is known to be associated with the intervention or population under study.  
Classification of AE Severity:

Mild: Awareness of signs or symptoms, but easily tolerated and are of minor irritant type causing no 
loss of time from normal activities. Symptoms do not require therapy or a medical evaluation; signs 
and symptoms are transient – i.e. no doctor visit or medical treatments were required.

Moderate: Events introduce a low level of inconvenience or concern to the participant and may 
interfere with daily activities, but are usually improved by simple therapeutic measures; moderate 
experiences may cause some interference with functioning – i.e. minimal medical treatment was 
needed, possible doctor visit or physical therapy. 

Severe: Events interrupt the participant’s normal daily activities and generally require systemic drug 
therapy or other treatment; they are usually incapacitating – i.e. medical attention was required, 
possible hospitalization.
Note: Severity is not synonymous with seriousness. SAEs are a subset of the reported AEs.
1.3  Protection Against Study Risks
Informed Consent Process: 
1) The study interviewer will conduct the initial telephone-screening interview. Study interviewers will conduct 
an oral consent process over the telephone prior to asking any study related questions. Following the 
interview, potential subjects will be invited for further in-person evaluations. Study consent, evaluations, 
enrollment, and in-person interventions will be done at our research center. 
2) The consent process will take place prior to initiating any study related evaluations or interventions and will 
inform a potential participant about the study. It indicates the participation is voluntary and he/she has the 
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right to stop at any time. Risks are enumerated in the informed consent form and described orally during 
the consent process.
Protection Against Risks: 
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 participants express physical or mental tiredness or 
discomfort during any of the assessments or training procedures, the procedure will be terminated 
immediately. Drs. Verghese or Blumen will be available onsite or by cellular telephone at all times to address 
any safety concerns or clinical issues during the interventions.
i)
Falls: Recent dance interventions using similar protocols in cognitively healthy and impaired 
participants report no or low rate of falls during dance sessions.34, 107 The rate of falls was <1% 
among 5,500 participants from 11 diverse physical activity interventions participating in a trans NIH 
collaborative known as the Behavior Change Consortium. 108 A Cochrane review of interventions to 
promote physical activity reported that of the 8 physical exercise trials with information on adverse 
events, fall rates were only significantly different from controls in 1 out of these 8 studies.109 Another 
Cochrane review that addressed the role of exercise programs (mostly walking but no dancing 
interventions) for people with dementia concluded that exercise was not harmful though the 
cognitive benefits were not proven.110 
Despite the low fall rate in these previous reviews, we take safety seriously, and have instituted a 
number of procedures to minimize fall risk in our pilot trail. Both the dance and walking groups are 
closely supervised. The groups are small so that instructors can pay attention to the participants, 
and intervene if balance problems are noted during the session. Participants will be instructed to 
wear sports shoes with good grip soles. Footwear and clothing will be inspected by the instructors 
prior to the start of sessions to ensure that they are appropriate for both intervention activities.  
Wooden complaint flooring used in our dance space is associated with lower risk of fall injury than 
hard flooring, though not as low as carpeted wooden flooring.111, 112 However, carpets were reported 
to be associated with falls in a Cochrane review of studies.113 It would not be practical to have 
safety harnesses on participants in the dance group, and this has not been the practice in the 
multiple previous dance intervention studies. Participants in both groups will be frequently asked 
about their comfort/discomfort levels.  The intervention will be stopped if participants report any 
unsteadiness or balance problems, and will be examined by the study clinician. Our research center 
is located within a hospital complex, and referral to primary care physician or emergency room will 
be done as required. 
ii)
Musculoskeletal injuries: Given the sedentary nature of our participants, musculoskeletal symptoms 
or injuries may occur. Previous studies suggest that though musculoskeletal complaints are 
common in physical activity interventions, the majority of these issues are mild in nature.108 Both the 
dance and walking groups are closely supervised. The groups are small so that instructors can pay 
attention to the participants. Participants are frequently asked about their comfort/discomfort levels 
including the Borg scale.  The intervention will be stopped if participants report any discomfort, and 
will be examined by the study clinician. Our research center is located within a hospital complex, 
and referral to primary care physician or emergency room will be done depending on the severity of 
the problem. 
iii) Neuroimaging results: Dr. Blumen will be immediately contacted in the event that an acute imaging 
finding requiring immediate action is discovered. She will review the reports of all MRI studies. 
Participants with normal studies will receive a letter to this effect. In the event that a non-urgent 
significant abnormality is discovered, Dr. Verghese will contact the participant by telephone to 
discuss the findings and advise that appropriate follow-up be obtained. A follow-up letter 
summarizing the discussion will be sent to the participant. If the participant wishes, the report will be 
sent to the primary care doctor.
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iv) MRI Safety program: A comprehensive MRI safety program is in place including secure access to 
the MRI suite and ongoing surveillance for effectiveness of the safety program. A board certified 
subspecialty neuroradiologist will review each MRI scan for pathology and confirm that there are no 
clinically significant findings for any of the participants. All data are archived in the Picture Archival 
and Communication System (PACS) and if needed can be archived in DVD-R media and stored in 
a locked cabinet.
2.0 Data and Safety monitoring 
All data collection in this clinical trial will be monitored to assure subject comfort, safety, and confidentiality. 
The clinical trial protocols, data collection instruments, subject recruitment letters, and consent forms will be 
reviewed and approved by the IRB. The NIA will also approve the creation and structure of the DSMP. 
The PIs will be responsible for ensuring participants’ safety on a daily basis. The SO will advise the NIA 
Program staff and the PIs regarding participant safety, participant risks and benefits, scientific integrity and 
ethical conduct of a study.
2.1 Frequency of Data and Safety Monitoring 
Safety Reports will be sent to the SO twice a year and will include a detailed analysis of study progress, data 
and safety issues.  
All deaths will be reported within 24 hours of study’s knowledge of death. The report of death will be submitted 
to the NIA Program Officer and to the SO. When SAEs occur that are unanticipated and that are related to the 
intervention, they will be reported to NIA Program Officer and to the SO within 48 hours of the study staff’s 
knowledge of SAE. The summary of all other SAEs will be reported in Safety Reports bi-annual reports. 
2.2 Content Safety Report 
At bi-annual intervals, the study team will prepare Safety Reports to be reviewed by the SO and NIA for 
recommendations for or against the trial’s continuation, as well as any modification to the study. An open (i.e., 
not segregated by treatment) and closed (i.e., coded by treatment assignment (social dancing or treadmill 
walking)) report will be submitted to the SO. The contents of the reports will focus on patient accrual and 
demographics, data completeness, and other study performance measures. The closed report will additionally 
divide study participants according to treatment comparing participant demographics and baseline 
characteristics, rates and reasons for treatment discontinuation and loss to follow-up, and rates of serious 
adverse events. In addition, the PIs may prepare a section of the report addressing concerns they anticipate 
will have regarding the conduct of the study. 
The reports will include:

Monthly and cumulative accrual

Baseline characteristics, overall and by treatment group

Summary of completeness and quality of data collection forms

Status of enrolled patients, 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

Sample size assumptions 

Outcome rates, overall and by treatment group along with monitoring boundaries for efficacy and futility 

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 adverse events
Only the closed report will include the comparisons by treatment group.
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2.3 Safety Officer Description and Affiliation
The following individual has accepted position as SO. The SO will be reviewed and approved by the NIA. 
Should there be any questions regarding the independence of the SO, it will be addressed and corrected if 
necessary at that time. 
Name: Preeti Raghavan, M.D.
Title, Organization: Associate Professor of Rehabilitation Research, Department of Rehabilitation Medicine, 
NYU Langone Hospital; Vice Chair for Research, Department of Rehabilitation Medicine, NYU Langone 
Hospital; Director, Division of Motor Recovery Research, NYU Langone Hospital
Brief Description of qualifications/reason for role as SO: 
Dr. Raghavan specializes in rehabilitation for patients recovering from stroke and traumatic brain injuries, as 
well as people with neurological conditions. She also conducts research to investigate how neurological 
injuries affect motor skills in the upper extremities. Her experience in these roles has provided her with the 
qualifications and clinical expertise necessary to serve as the SO on this clinical trial involving complex 
sensorimotor activity.
2.4 Conflict of Interest for the SO
The SO has no direct involvement with the study investigators or intervention, and will sign a Conflict of 
Interest Statement which includes current affiliations, if any, with pharmaceutical and biotechnology companies 
(e.g., stockholder, consultant), and any other relationship that could be perceived as a conflict of interest 
related to the study and / or associated with commercial interests pertinent to study objectives.
 
2.5 Protection of Confidentiality 
Data will be presented in a blinded manner in the open report for the SO, data and discussion are confidential. 
Participant identities will not be known to the SO.
2.6 SO Responsibilities
It is the responsibility of the SO to:
•
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.
 
4) Study Population 
a) We will enroll 32 dementia at-risk seniors over 2 years. Our sample size is not based on demonstrating 
clinical efficacy but to obtain preliminary data and feasibility to plan our RO1. 
b) General inclusion criteria:  
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i)
Adults aged 65 and older. The age criterion is intended to maximize observed rates of age relate 
decline in executive function. 
ii)
At-risk for dementia defined as meeting cutscores on either the MIS (≤ 6)38 or AD-8 (≥ 1)39 tests 
administered by telephone. 
iii) Plan to be in area for next year or more. 
iv) Able to speak English at a level sufficient to undergo our interventions and cognitive assessment 
battery. 
v)
Willing to complete an MRI (exclusions relevant to neuroimaging are described below). Given our 
small sample size and budget limits of the R21 format we wanted to maximize study and budgetary 
efficiency by enrolling participants who not only agree to the study interventions but also agree to 
undergo neuroimaging. 
c)
General exclusion criteria (one or more criteria): 
i)
Presence of dementia based on telephone interview, previous established physician diagnosis of 
dementia or dementia diagnosed by Dr. Verghese at initial visit. 
ii)
Serious chronic or acute illness such as cancer (late stage, metastatic, or on active treatment), 
chronic pulmonary disease on ventilator or continuous oxygen therapy or active liver disease. 
Individuals with recent cardiovascular or cerebrovascular event (MI, PTCA, CABG, or stroke) will 
not be excluded if they meet above inclusion criteria. Many of these chronic conditions are very 
common in older adults. Hence, mere presence of these conditions will not be used to exclude 
subjects if well controlled or of mild severity and if subjects are able to complete the interventions.
iii) Mobility limitations solely due to musculoskeletal or cardiovascular conditions that prevent 
participation in the intervention programs. Prevalence of arthritis is ~60% in the Einstein Aging 
Study35, so mere presence of disease will not be used to exclude subjects if they can complete the 
mobility tasks. Screening clinician will assess and document presence of musculoskeletal diseases.
iv) Any medical condition or chronic medication use (e.g., neuroleptics) in the judgment of the 
screening clinician that will compromise safety or affect cognitive functioning.
v)
Terminal illness with life expectancy less than 12 months. 
vi) Progressive, degenerative neurologic disease (e.g., Parkinson’s disease or ALS) diagnosed by 
Dr. Verghese and as per medical history that will restrict mobility and participation in interventions.
vii) Severe auditory or visual loss: Vision is screened using a Snellen chart by the psychological 
assistant. Also, the neurologist tests visual fields using confrontation perimetry and near vision 
using Jaeger test types. Significant loss of vision is defined as corrected vision (using reading 
glasses) less than 20/400 on the Snellen chart with both eyes and inability to read any test 
sentence on the Jaeger test card with both eyes. Hearing is initially evaluated as part of the 
screening telephone interview. Subjects who attend the clinic visit will be excluded only if they are 
unable to follow questions asked in a loud voice (even with hearing aid in place).
viii)Active psychoses or psychiatric symptoms (such as agitation) noted during the clinic visit that 
will prevent completion of study protocols. Past history of these symptoms or presence of 
psychiatric illness not used as exclusion criteria. 
ix) Either participation in competitive dancing or recreational dancing at a frequency >1/month 
in the past six months. As seniors may dance at social events (but not at doses or frequency to 
have cognitive benefits), excluding all seniors who ever danced is not practical. We will examine all 
reports of participation in cognitive enhancement programs (as this covers a wide range of 
activities) to judge inclusion.
x)
Participation in other interventional study that overlaps with intervention period of this 
study.
d) Specific Neuroimaging considerations: Additional exclusions relevant to neuroimaging include the 
presence of any surgically implanted metallic devices, such as aneurysm clips or pacemakers that 
would be a safety contraindication for MRI. Subjects with large amounts of dental or surgical hardware 
in the head and neck will be excluded because magnetic susceptibility effects will lead to severe image 
artifacts in these subjects' images.  Due to the confined space of the MRI magnet, subjects with a 
known history of claustrophobia will also be excluded as will subjects with weight >350lbs or waist 
circumference >55 inches.  Conditions that may confound the association between neuroimaging 
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cognition and mobility (normal pressure hydrocephalus or severe head trauma) will be excluded from 
analyses. We estimate that the prevalence of these conditions is very low based on other aging studies. 
Additional incidental findings that may be seen with a low prevalence in the elderly may include 
vascular anomalies or tumors. All scans will be reviewed by board-certified neuroradiologists. Abnormal 
results will be communicated to Dr. Verghese who will initiate follow-up with subjects and their 
physicians as has been our established procedure in other studies based in our center.
e) 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.
f)
Research material obtained from human subjects will be the results of clinical and neuropsychological 
testing obtained from study assessments and telephone interviews. The subject and their primary care 
physician will be informed of all clinical results that are relevant to patient care. Phenotypic data will 
also include results of MRIs, questionnaires, and body composition tests.
5) Participant Recruitment 
a) To achieve our study aims 32 participants will be recruited at random from commercially available lists of 
Bronx and Westchester County residents over the two-year funding period.  We will also recruit 
participants from the Montefiore Medical Center Geriatrics and primary care clinics that have over 20,000 
visits by patients, age 65 and older. We have had experience using both the community and clinic sources 
to recruit over participants for various aging studies in the past 10 years. Once telephone contact is 
achieved and the interview is complete, we assume that there will be a 20% loss due to lack of interest 
in the study and failure to meet general eligibility requirements and an additional 10% failure on the 
cognitive instruments (MIS or AD-8). There is an additional 10% loss in the remaining sample due to 
failure to meet eligibility requirements. Using telephone based recruitment instruments enables us to 
minimize loss due to not meeting criteria on in-person assessments. 
A concern is that there might be attrition between the enrollment and start of the intervention in 
this high-risk group. To minimize this possibility, we will institute a rolling admission policy that we have 
successfully used in our ongoing cognitive remediation study.114 A different dance is taught in each 
session. As soon as we have enrolled a pair into the dance group, they will start the dance program in 
the next available day. This modified rolling admission policy will help reduce delays between enrollment 
and the start of the dance intervention. In the walking group, the intervention is individualized though 
participants exercise in groups on the treadmill to simulate the social nature of dancing. Hence, 
participants randomized to the walking arm can join the walking program at any point during the 2-year 
study period. Participants randomized to the walking group will also start the program at the next available 
day. 
6) Informed Consent 
a) The study interviewer will conduct the initial telephone-screening interview. Potential subjects will be 
invited for further in-person evaluations. Study evaluations, enrollment, and in-person interventions will 
be done at our research center. Dr. Verghese and the research assistant and will diagnose and exclude 
cases following clinical and neuropsychological testing. 
b) Compensation at $10/session consistent with IRB guidelines will be provided to participants. An 
additional $25 will be provided to participants for completing each MRI. 
7) Risk/Benefit 
a) Potential risks: We do not expect any serious adverse events during these non-invasive tests and 
training programs of attention and executive function. Answering health questionnaires and mental state 
examinations involve minimal psychological, social, or other risks. 
i)
Dance classes will be taught by certified dance instructors (with experience teaching seniors) at 
varying levels of complexity and the progression during the intervention period will be gradual. 
Progression to new dances will take into account the balance challenge, cardiovascular demand, 
degree of flexibility, coordination and cognitive demand. The instructor will ensure that the programs 
will not be manipulated to mimic exercise training as in aerobic dance classes. 
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ii)
The treadmill training walking intervention protocol will be based on recommendations of the 
American College of Sports Medicine (ACSM)106 and American Heart Association (AHA) for older 
adults. A gradual approach will be applied to increase exercise intensity in participants with a low 
baseline level of physical activity and who may be unfamiliar with treadmill walking. Pulse and blood 
pressure will be assessed before and after each session to assure that the values are not deviated 
by 10 or more from the values of initial assessment for pulse and systolic blood pressure. During 
exercise, participants are monitored with the subjective Borg scale68 every 5 minutes and heart rate 
is tracked by a physical therapist. Participants are encouraged to increase the training velocity if the 
subjective rating of exercise intensity is low (fairly light, Borg score <12). The treadmill speed will be 
reduced or exercise aborted if there are any untoward symptoms such as cardiovascular symptoms 
or excessive fatigue. Heart rate will be measured during the break between training periods and the 
second period will only be initiated after the value is below the 70% of estimated maximum heart 
rate.106 Similar procedures will also be followed in the dance intervention group.
Since there are no significant risks associated with the procedures, this study is justified because 
useful new scientific knowledge will be obtained.
b) Protection against risk: 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. Verghese, Blumen or the supervising investigator for 
each arm will be available onsite or by cellular telephone at all times to address any safety concerns or 
clinical issues during the interventions.
i)
Fall safety: Recent dance interventions using similar protocols in cognitively healthy and impaired 
participants report no or low rate of falls during dance sessions.34, 107 The rate of falls was <1% among 
5,500 participants from 11 diverse physical activity interventions participating in a trans NIH 
collaborative known as the Behavior Change Consortium. 108 A Cochrane review of interventions to 
promote physical activity reported that of the 8 physical exercise trials with information on adverse 
events, fall rates were only significantly different from controls in 1 out of these 8 studies.109 Another 
Cochrane review that addressed the role of exercise programs (mostly walking but no dancing 
interventions) for people with dementia concluded that exercise was not harmful though the cognitive 
benefits were not proven.110 
Despite the low fall rate in these previous reviews, we take safety seriously, and have instituted 
a number of procedures to minimize fall risk in our pilot trail. Both the dance and walking groups are 
closely supervised. The groups are small so that instructors can pay attention to the participants, and 
intervene if balance problems are noted during the session. Participants will be instructed to wear 
sports shoes with good grip soles. Footwear and clothing will be inspected by the instructors prior to 
the start of sessions to ensure that they are appropriate for both intervention activities.  Wooden 
complaint flooring used in our dance space is associated with lower risk of fall injury than hard flooring, 
though not as low as carpeted wooden flooring.111, 112 However, carpets were reported to be 
associated with falls in a Cochrane review of studies.113 It would not be practical to have safety 
harnesses on participants in the dance group, and this has not been the practice in the multiple 
previous dance intervention studies. Participants in both groups will be frequently asked about their 
comfort/discomfort levels.  The intervention will be stopped if participants report any unsteadiness or 
balance problems, and will be examined by the study clinician. Our research center is located within 
a hospital complex, and referral to primary care physician or emergency room will be done as 
required. Our safety experience in this pilot trial will inform the design and conduct of our full scale 
RO1.
ii)
Musculoskeletal injuries: Given the sedentary nature of our participants (new criterion included as 
suggested by reviewer), musculoskeletal symptoms or injuries may occur. Previous studies suggest 
that though musculoskeletal complaints are common in physical activity interventions, the majority of 
these issues are mild in nature.108 Both the dance and walking groups are closely supervised. The 
groups are small so that instructors can pay attention to the participants. Participants are frequently 
asked about their comfort/discomfort levels including the Borg scale.  The intervention will be stopped 
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if participants report any discomfort, and will be examined by the study clinician. Our research center 
is located within a hospital complex, and referral to primary care physician or emergency room will 
be done depending on the severity of the problem. 
iii) Neuroimaging results: Dr. Blumen will be immediately contacted in the event that an acute imaging 
finding requiring immediate action is discovered. She will review the reports of all MRI studies. 
Participants with normal studies will receive a letter to this effect. In the event that a non-urgent 
significant abnormality is discovered, Dr. Verghese will contact the participant by telephone to discuss 
the findings and advise that appropriate PMD follow-up be obtained. A follow-up letter summarizing 
the discussion will be sent to the participant. If the participant wishes, the report will be sent to the 
PMD.
iv) MRI Safety program: A comprehensive MRI safety program is in place including secure access to the 
MRI suite and ongoing surveillance for effectiveness of the safety program. A board certified 
subspecialty neuroradiologist will review each MRI scan for pathology and confirm that there are no 
clinically significant findings for any of the participants. All data are archived in the Picture Archival 
and Communication System (PACS) and if needed can be archived in DVD-R media and stored in a 
locked cabinet.
v)
Columbia Univerisity, NY: Yunglin Gazes, Ph.D. is an Assistant Professor of Neuropsychology in the 
Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging 
Brain at Columbia University. She will be responsible for supervising the neuroimaging component of 
this RCT. She has considerable experience with forms of advanced neuroimaging analyses described 
in this project and has previously collaborated with Dr. Blumen (co-PI) on several projects using 
similar neuroimaging techniques. She will conduct and monitor neuroimaging analyses, assist in 
preparation of manuscripts and present findings at scientific meetings.
vi) Benefits: Our previous experience, the non-invasive nature of most proposed procedures, the 
widespread prevalence of dance and exercise programs in the community, the general acceptance 
by practicing physicians of the procedures to be used, and the close supervision and monitoring of 
the subjects all minimizes the potential risks. Both dancing and walking may improve physical fitness, 
and involve minimal risks to the participant. Early diagnosis and treatment of disorders discovered as 
a result of screening done in these studies may impact beneficially on their health. In addition, 
understanding of the role of physical, mental, and social activities in ameliorating age-related 
cognitive decline could provide important insights into the aging process and age-related diseases 
that could ultimately have a positive impact on the length and quality of life for study subjects. 
c)
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 the statistician will have 
access. Randomization procedures were discussed previously. 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 written request, to the Institutional Review Board (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. 
i)
Participants will be recorded as they walk on the gait mat. No sound will be recorded. The videos will 
not be destroyed. The tapes will be used by the research team to score the evaluations and refine 
measurements already collected. Participants will not receive any monetary compensation for being 
taped.
8) Data Analysis: Study outcomes will be assessed at baseline, month 2, 4, immediate post-intervention 
(month 6), and month 9. Attendance rates will be reported. The purpose of the analyses are to estimate 
effects that can be used for a larger confirmatory study.
a) Aim 1: Linear mixed effects models will be used to compare the trajectories of composite EF score at 
baseline and months 2/4/6/9.  The optimal treatment period that yields the greatest treatment effect will 
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be identified. Estimates with 95% CI of dance effects at different time points as well as slope of change 
will be reported. The analysis will also be applied to individual EF tests to examine whether the dance 
effects differentiates among different aspects of EF.
o
Pre-specified covariates115-117 to account for confounding include age, gender, education and 
chronic illnesses.118 Baseline distribution of covariates will be compared to assess adequacy of 
randomization. We do not discount residual/unmeasured confounding – though this is more of an 
issue in observational studies without randomization. 
o
Intensity (actigraphy in-session) and dose (number of sessions) of dance and walking will also 
be examined. 
Power: The pilot sample size was based on pragmatics of recruitment and necessities for examining 
feasibility.119 Based on previous studies, we expect correlations of at least 0.80 between repeated EF 
scores. With 16 in each group and assuming 20% drop out rate at post intervention, we can detect a 
difference of 0.075 SD per month in EF slope using measurements at baseline/2/4/6 months, between 
groups with 80% power using 2-sided tests with alpha level 0.05. 
b) Aim 2: The comparison of imaging measures pre-post intervention (month 0 vs. 6) between study arms 
will be analyzed using multivariate covariance-based analyses, adjusting for age, gender and other 
covariates. Multivariate covariance-based analyses are particularly sensitive to detecting effects in the 
presence of between-subject variability and collinearity– issues particularly important to consider in aging 
populations and with neuroimaging data. Drs. Blumen and Gazes have considerable experience with 
these neuroimaging analyses.96, 120-127 Mean and confidence intervals of imaging measures within each 
group as well as the difference between the two groups will be reported for performance at each time 
point of pre and post intervention, and for change at post from pre intervention. 
o
fMRI: WWT imagery task, DSST and Flanker Task. Standard pre-processing and first-level 
analyses will be performed with SPM12 (see Equipment). Group-Level Covariance Analyses. 
Ordinal Trend Covariance Analyses (OrT-CVA; http://www.nitrc.org/projects/gcva_pca) will be 
used to analyze the imagined WWT, DSST and Flanker Tasks128, 129. OrT-CVA will be used to 
identify covariance patterns in the fMRI signal as a function of trial type (iT, iW and iWWT on the 
imagined WWT, task and rest blocks on the DSST, incongruent and congruent trials on Flanker 
Task) at each study visit (pre and post-intervention). OrT-CVA employs a 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 (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 & 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. Each intervention group will be split into two, and split 
half-reliability assessed by correlations on imaging measures. 
Power: The sample of 16 per group is within the number recommended to conduct reliability studies130 
and to improve study design.131 We will report estimates of imaging measures to improve study design 
of our full scale RCT. 
c)
Potential pitfalls and solutions. We recognize that despite all our efforts, there will be missing data. 
To address this issue we will identify contact persons. Flexible scheduling with makeup sessions is 
provided. We will not restrict participation in outside activities keeping with the pragmatic nature of the 
trial.  We will track outside activities using validated leisure and activity scales (see Table 1) to see if it 
will explain durability of any observed effects.
9) Data quality control and database management
a) The content captured will consist of demographics, medical history, MRIs, laboratory data, clinical and 
biological safety outcomes and adherence data.  Data management will incorporate the expertise of the 
Research Informatics Core (RIC), a component of the Einstein-Montefiore Institute for Clinical and 
Translational Research (ICTR) consisting of developers and database analysts who specialize in the 
management of research data.  REDCap (Research Electronic Data Capture) is a mature, secure, web-
based application for building and managing online surveys and databases developed by Vanderbilt 
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University to support the electronic collection and management of clinical research data. It has been 
available at Einstein-Montefiore since it became REDCap consortium member in 2010. 
REDCap can be used to collect virtually any type of data (including 21 CFR Part 11 and FISMA-
compliant environments), but it is specifically geared to support online or offline data capture for 
research studies and operations, being by design HIPAA-compliant. REDCap's streamlined process for 
rapidly developing projects helps to create and design projects using 1) the online method from a web 
browser using the Online Designer; and/or 2) the offline method by constructing a 'data dictionary' 
template file in Microsoft Excel, which can be later uploaded into REDCap. Both surveys and Data 
Collection Forms (or a mixture of the two) can be built using these methods. REDCap provides an 
intuitive interface for users to enter data and have real time validation rules (with automated data type 
and range checks) at the time of entry.  This system offers easy data management with audit trails for 
reporting, monitoring and querying participant records.  REDCap provides automated export 
procedures for seamless data downloads to Excel and common statistical packages (SPSS, SAS, 
Stata, R), as well as a built-in project calendar, a scheduling module, ad hoc reporting tools, and 
advanced features, such as branching logic, file uploading, and calculated fields.   
REDCap servers are housed in a data center at Einstein and all web-based information 
transmission is encrypted.  REDCap was developed specifically around HIPAA-Security guidelines.  It 
currently supports 2394 academic/non-profit consortium partners and over 500,000 research end-users 
(www.project-redcap.org). A member of the study team will enter all data into this web-based system.  
The RIC will assist with the design of the data collection forms, implement protocols for data QA, 
access permissions, and production of customized reports and datasets for biostatistical analysis.  All 
data collection procedures will be closely monitored to ensure that data integrity is maintained.  
10)References
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Verghese J, Lipton RB, Katz MJ, Hall CB, Derby CA, Kuslansky G, et al. Leisure activities and the risk 
of dementia in the elderly. The New England journal of medicine. 2003;348(25):2508-16. doi: 
10.1056/NEJMoa022252. PubMed PMID: 12815136.
2.
Blasing B, Calvo-Merino B, Cross ES, Jola C, Honisch J, Stevens CJ. Neurocognitive control in dance 
perception and performance. Acta psychologica. 2012;139(2):300-8. Epub 2012/02/07. doi: 
10.1016/j.actpsy.2011.12.005. PubMed PMID: 22305351.
3.
Brown S, Martinez MJ, Parsons LM. The neural basis of human dance. Cereb Cortex. 2006;16(8):1157-
67. Epub 2005/10/14. doi: 10.1093/cercor/bhj057. PubMed PMID: 16221923.
4.
Brown S, Parsons LM. The neuroscience of dance. Scientific American. 2008;299(1):78-83. Epub 
2008/07/16. PubMed PMID: 18623968.
5.
Kattenstroth JC, Kalisch T, Kolankowska I, Dinse HR. Balance, sensorimotor, and cognitive 
performance in long-year expert senior ballroom dancers. Journal of aging research. 2011;2011:176709. Epub 
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10.1136/bmj.i5239. PubMed PMID: 27777223; PMCID: PMC5076380 http://www.icmje.org/coi_disclosure.pdf 
and declare support from the following organisations for the submitted work-Queen Mary University of London, 
University of Sheffield (ScHARR Research Committee Pump priming grant), NIHR Research Design Services 
London and South East, NIHR Statisticians Group, Chief Scientist Office Scotland. GAL is editor in chief of the 
new BioMed central journal Pilot and Feasibility Studies proposed by Daniel R Shanahan, which was created 
out of this work. Daniel R Shanahan is employed by BioMed Central, and Trish Groves is an editor of the BMJ. 
SME, CMB, MJC, and LT are on the editorial board of Pilot and Feasibility Studies and CLC is an associate 
editor. Frank Bretz works for Novartis. The authors declare no other competing interests. None of the listed 
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Amendments

9/17/2018 – The Data and Safety Monitoring Plan (DSMP) section is revised to be consistent with the 
DSMP approved by the NIA.
o
A DSMB is not required, but a SO is named.
o
Definitions and reporting guidelines for AEs are described per NIA policy.
IRB NUMBER: 2018-8942
IRB APPROVAL DATE: 09/24/2018