Prevention of Early Postoperative Decline
Phase: NA
Conditions: Delirium, Postoperative Cognitive Dysfunction
Sponsor: Beth Israel Deaconess Medical Center

(CCI) Committee on Clinical Investigations 
Page 1 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
 
 
 
 
 
 
Prevention of Early Postoperative 
Decline 
 
NCT# 02908464 
 
September 25, 2017 
 

(CCI) Committee on Clinical Investigations 
Page 2 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
Prevention of Early Postoperative Decline 
Principal Investigator 
Brian O’Gara MD 
 
 
B1. 
PURPOSE OF PROTOCOL 
Hypothesis:  
Patients undergoing cardiac surgery have a high risk of postoperative cognitive decline.  Patients who 
participate in a neurocognitive training program pre- and post-operatively will have a lower incidence of 
postoperative cognitive decline after cardiac surgery than do controls receiving standard of care.    
 
Specific Aim: 
A feasibility study aiming to outline subject interest, adherence to protocol and generation of preliminary 
data regarding the ability of a neurocognitive training program to reduce the incidence of postoperative 
cognitive decline after cardiac surgery.   
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
 
Exposure to surgical stress and general anesthesia is associated with the occurrence of 
postoperative cognitive decline (POCD), with an incidence found to be between 26-40% after the first 
postoperative week and 15% incidence after three months compared to age matched controls (Moller 
1998, Ballard 2012).  POCD has been found to be especially prevalent after cardiac surgery, with 
incidences reported between 30-80% in the first postoperative week and persistent decline found in 
24% of patients at six months (Arrowsmith 2000, Newman 2001).  A number of surgical, 
inflammatory, and anesthetic factors are thought to be associated with the increased incidence of 
POCD in this group of patients, but so far preventative strategies targeting these areas have not been 
shown to be effective. 
With the increasing age and number of comorbid conditions of the cardiac surgical patient in today's 
health care climate, a new focus for the perioperative team has been optimizing the preoperative 
condition of the surgical patient through prehabilitation.  While promising results have been shown 
through preoperative physical prehabilitation programs, to date there has been no recommendation 
for cognitive prehabilitation for cardiac surgical patients to minimize the severity or reduce the 
incidence of POCD (Debes 2014).  Similarly, while the need for physical rehabilitation to recover from 
the physical stress of cardiac surgery is a well-established and integral aspect of each patient’s 
hospital care and discharge planning, a regimen focused on neurocognitive rehabilitation is not 
prescribed.     
Specific areas of cognition thought to be most affected in the postoperative period include attention, 
working memory, orientation, and speed of processing (Newman 2001, Hudetz 2009, Saczynski 
2012).  Lumosity, a neuroscience-based training program, has been shown in various studies to 
improve subjects' cognitive performance in many of the same cognitive areas (Mayas 2014, 
Ballesteros 2014, Hardy 2015).  We hypothesize that pre- and post-operative training with tailored 
neuroscience programs provided by Lumosity will result in a decreased incidence of POCD.    
 

(CCI) Committee on Clinical Investigations 
Page 3 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
Research Question: 
Does prehabilitation with Lumosity neuroscience training programs reduce the incidence of 
postoperative cognitive decline after cardiac surgery? 
Study Design Overview:   
Prospective, randomized, assessor-blinded feasibility trial.  Enrolled patients will be randomized into 
one of two research arms: Neurocognitive training with Lumosity or no training (standard of care 
control group).  Subjects will then be assessed for the development of postoperative cognitive decline 
and the incidence of delirium in the postoperative period up until postoperative day 7 or discharge, 
whichever comes first.  Subjects will also undergo repeat neurocognitive assessment at 1, 3, and 6 
months postoperatively, and complete a Patient Satisfaction Survey at 1-month post-operatively.     
Methods: 
Preoperative Study Procedures: If deemed a candidate for enrollment, patients will be approached by 
study personnel to discuss the study in an informed consenting conversation.  Once informed consent 
has been obtained, baseline assessment of cognitive function for both groups will take place at that 
time and patients with severe baseline cognitive impairment will be excluded.  Subjects will then be 
randomized into either the intervention or control group.  Cognitive assessments for the primary 
outcome in this study will be conducted with the Montreal Cognitive Assessment (MoCA), which has 
been shown in randomized study to be both highly sensitive and specific for the identification of mild 
cognitive impairment as compared to the mini mental status exam (Nasreddine 2005). 
Creation of Lumosity Accounts:  Once enrolled, subjects in the treatment group will be assigned a 
specific, anonymized user name and email address to use while accessing the Lumosity training 
program.  Subscriptions to the service will be offered free of charge to the subject without the need for 
identifying information to be shared with the company by virtue of a pre-existing research agreement.    
Intervention: Subjects randomized to the treatment group will undergo 30-45 minutes a day total of 
Lumosity neuroscience training for at least 10 days preoperatively, then for 4 weeks postoperatively.  
Subjects will be expected to complete at least two 15 minute sessions of Lumosity training per day, 
but will be limited to a maximum of three sessions per day to minimize long term fatigue in completing 
the protocol.  Subjects randomized to the control group will not participate in Lumosity training. 
TREATMENT GROUP: 
Lumosity Neurocognitive training program: Subjects will undergo at least two 15-minute training 
sessions a day utilizing a customized training package provided by Lumosity designed to target 
the areas of cognition thought to be most affected in the perioperative period based on prior 
study (Newman, Hudetz, Sacynski).  Subjects will be expected to train for at least 10 days 
preoperatively and then for four weeks postoperatively.  Subscription and access to the training 
programs will be provided free of charge from the company on iPads, provided by the BIDMC 
Center for Anesthesia Research Excellence group.  

(CCI) Committee on Clinical Investigations 
Page 4 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
 
Protocol Adherence: Login details, time spent training, and scoring performance statistics will be 
provided for each user by the Lumosity company via email to the study team.  Subject data will 
be de-identified for this purpose and only subject username and email address will be used to 
identify the users in each case.  
CONTROL GROUP: 
Control Condition: Subjects in the control group will be required to refrain from creating a 
Lumosity account and using their program during the course of the study.  They will otherwise 
prepare for cardiac surgery and undergo perioperative care according to the current standard of 
care.  To date there are no formal recommendations for neurocognitive preparation or 
rehabilitation in the perioperative cardiac surgical period.       
Assessments: A baseline MoCA will take place on the day of informed consent as described above, 
after enrollment but before randomization.  On the day of surgery (or when the subject is admitted for 
surgery), a repeat MoCA will take place.  Cardiac surgery and anesthesia care will proceed in the 
usual fashion according to current hospital standards, which includes general anesthesia and 
cardiopulmonary bypass.  Patients will be assessed for the presence of POCD and delirium in the 
postoperative period using two commonly used methodologies: MoCA and the Confusion 
Assessment Method (CAM).  The MoCA will then again be completed on postoperative day (POD) 7 
or discharge (whichever comes first), in order to identify trends in POCD.  The MoCA will not be used 
daily during the postoperative period so as to minimize learning effect on test performance.   
Delirium assessment will take place every postoperative day until day 7 or discharge (whichever 
comes first) with the use of the CAM or CAM-ICU assessment tool, which has been used extensively 
in the hospital setting to identify delirium (Wei 2008).  To improve the sensitivity of the delirium 
assessments, a delirium symptom interview (DSI) will also be performed in conjunction with the 
CAM/CAM-ICU assessments.     
Once the patient is discharged, a telephonic version of the MoCA will take place at 1 month (+/- 7 
days), 3 months (+/- 14 days), and 6 months (+/- 14 days) postoperatively.  Should a subject return a 
phone call from the research team outside of the allowable window, the assessments will still occur 
and the data obtained will be used.  A patient satisfaction survey will be administered at the patient’s 
1-month follow-up which will be entered directly into REDCap. If the patient is unable to complete the 
survey at the visit, a link directly to the anonymous REDCap survey will be emailed to them. 
Data to be Collected:  Additionally, to track other important factors related to patient outcome and 
protocol adherence we may extract clinical data from the medical record such as: 
• 
Anthropometric data (e.g. age, height, weight, race/ethnicity) 
• 
Comorbidities 
• 
Admission type 
• 
Medications 
• 
Respiratory physiological data  
• 
Hemodynamic data (e.g. heart rate, blood pressure) 
• 
Laboratory data 
• 
Complications data  
• 
Hospitalization-related time data (e.g. admitting diagnosis, hospital and ICU length of stay) 
• 
Vital status 

(CCI) Committee on Clinical Investigations 
Page 5 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
Primary Outcome: 
Feasibility of utilizing an electronic neurocognitive training program preoperatively, during the hospital 
period, and postoperatively in a geriatric cardiac surgical population.  Feasibility will be assessed by 
the metrics of consent rates, protocol adherence rates, and patient satisfaction scores. 
Secondary Outcomes: 
Incidence of postoperative delirium 
- 
Defined according to the Confusion Assessment Method (CAM): 
o Acute onset and fluctuating course 
o Inattention 
AND EITHER 
o Disorganized thinking 
OR 
o Altered Level of consciousness 
- 
Assessed daily until day of hospital discharge 
- 
Assessments will take place using the CAM or CAM-ICU depending on patient condition 
 
Incidence of Postoperative Cognitive Dysfunction (POCD) 
- 
Defined by a decrease of 3 points or greater on the Montreal Cognitive Assessment from 
baseline 
- 
Assessed on day of hospital discharge, as well as 1 month, 3 months, and 6 months 
postoperatively 
- 
In person assessments of POCD will be performed using the MoCA, postoperative 
assessments at 1,3 and 6 months will be conducted with the telephonic MOCA version  
 
Study-Related Encounters: 
With a baseline assessment, an assessment on day of surgery, daily assessments on POD 1-6, POD 7 
or discharge, and assessments at 1, 3, and 6 months postoperatively, we anticipate a maximum of 12 
study related encounters per patient.   
 
Adverse Event Reporting: 
This patient population is undergoing high risk surgery and it is expected that they may have a number of 
unrelated adverse health events during their hospital course.  Therefore, we will limit the scope of AE 
monitoring and reporting to the following: 
• 
All Serious Adverse Events believed to be related to the study procedures 
• 
All non-serious Adverse Events believed to be related to the study procedures 
 
Adverse events will be assessed through the 6-month phone contact. 
 
B. 
Statistical Considerations 
a. Sample Size Justification:   
A convenience sample of 45 patients will be chosen in order to assess the feasibility of the Lumosity 
intervention.  A total of 20 enrolled and randomized subjects are needed per group in order to assess 
the rates of participation, adherence, and drop out associated with the study.  To account for patients 
who may fail the initial MOCA screen, or withdraw prior to randomization, we will add 5 patients to the 
desired enrollment sample size.  Data from these 45 patients will be used to adequately power a 
larger, likely multicenter trial, based on the treatment effect seen in the feasibility trial.   
 

(CCI) Committee on Clinical Investigations 
Page 6 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
b. Data Analysis:   
Data Analysis: Patients will be prospectively randomized using 1:1 block randomization of equal sizes.  
Analyses will be conducted using SAS version 9.3 (SAS Institute, Cary, North Carolina) or later.  
Descriptive statistics of the data will be performed.  Continuous data will be represented using mean (± 
standard deviation) or median (interquartile range) for variables not normally distributed and compared 
using parametric or non-parametric t-tests as appropriate.  Categorical data will be presented using 
proportions and compared using a chi-square or Fishers Exact test.  
 
Analysis of the Primary Outcome: 
The primary outcome of the study is feasibility.  Feasibility will be defined in terms of achieving 
satisfactory recruitment, adherence to protocol, and patient satisfaction.  Satisfactory recruitment will 
be defined as enrollment of greater than 50% of eligible patients during the study period.  Adherence 
to the protocol will be assessed using automated data reports of user activity generated in 
collaboration with Lumosity.  Per protocol patients are expected to complete the intervention twice 
daily for 10 days preoperatively and 4 weeks postoperatively unless they are incapacitated due to 
critical illness or intubated.  We will define satisfactory adherence as completion of the protocol for 
greater than 70% of days in which the patient maintains capacity and completes both sessions.  
Patient satisfaction will be assessed using qualitative data techniques including patient surveys and 
testimonials 
                                                                                                                                              
Analysis of Secondary Outcomes: 
Differences in the incidence of postoperative delirium and POCD will be presented as proportions and 
assessed with the use of a chi-square test.  Odds ratios and 95% confidence intervals will be reported 
and interpreted.  Although randomization should eliminate baseline confounders, univariate and 
multivariable logistic regression modeling may be employed to assess the relationship between 
preoperative luminosity use and both delirium and POCD, adjusting for any differences that may 
persist between groups. 
  
All data storage and analysis will take place on the BIDMC protected research server.  Once collected, 
patient data will be placed into a REDCap database.  Study staff at BIDMC will analyze all data from 
this project.      
 
 
C. 
Subject Selection 
 
Inclusion criteria: 
1. Adult age patients (60-90 years) undergoing cardiac surgery 
2. Adequate time to implement prehabilitation training intervention: at least 10 days from 
enrollment  
3. Educational attainment of at least a high school level of education or equivalent  
 
Exclusion criteria: 
1. Pre-existing history of psychiatric illness as documented in the medical record or divulged in 
history taking in pre-enrollment patient interview, such as anxiety, depression or bipolar 
disorder 
2. History of cerebrovascular accident or seizure, or a history of dementia, Parkinson’s disease, 
Alzheimer’s disease, other forms of cognitive decline  
3. Non-English speakers. (Justification: Lumosity tools are provided only in English; cognitive 
assessment instruments are not validated in a sufficient range of languages, and the research 
team lacks polylingual capabilities or the financial resources to hire interpreters for the 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
duration of all proposed assessments) 
4. Currently enrolled in another study assessing cognitive ability 
5. Significant visual impairment 
 
Drop Out Criteria: 
1. After recruitment, enrollment and randomization, patients will be withdrawn from the study if 
they have a baseline MoCA score of less than 10 as this indicates severe cognitive 
dysfunction.  
 
**Note:  If a patient meets inclusion criteria of being enrolled at least 10 days prior to surgery (adequate 
time to implement prehabilitation), and surgery is rescheduled to an earlier date by the clinical team, 
allowing less than 10 days of prehabilitation, the patient will continue in the study and will not be 
withdrawn. 
 
Patients will not be recruited on the basis of race, ethnicity, or gender.  However, it is not clear whether 
the final study sample will contain a representative spread of the BIDMC racial and gender makeup, as a 
result of the exclusion of non-English speaking patients. There is no reason to exclude pregnant women 
from this protocol. However, based on the study plan to recruit patients at highest risk for POCD, we will 
be recruiting from a patient pool generally exclusive of women of childbearing age largely based on the 
age requirement.  
 
B4. 
POSSIBLE BENEFITS 
As the proposed study is a feasibility trial, we do not anticipate any specific benefit to be gained by the 
individual subject, as the intervention in question has never been tested in this arena.  However, based 
on our hypothesis, if the intervention were to result in a lower incidence of post-operative cognitive 
decline, it can be reasonably inferred that the individuals who did not suffer from POCD would be able to 
enjoy a higher quality of life, be more functionally independent, and contribute to society in a manner in 
which they were accustomed to, more so than those who would be cognitively impaired after cardiac 
surgery.  Furthermore, as has been stated in this proposal, to date there are no specific 
recommendations or interventions prescribed for the prevention of POCD.  If the intervention were 
ultimately successful in a larger study, it could serve as the basis for a new area of perioperative 
medicine focusing in cognitive training to prevent POCD.  Lastly, the insight gained from the 
interpretation of categorical results from the MoCA assessment could provide further direction into the 
cognitive areas most affected in the post-operative period.                
 
B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
As there are no physical interventions planned in this study, we do not anticipate any risk of physical 
harm to any of the research subjects.  The training program has not been used in this arena prior to this 
study, therefore, there is no published information regarding psychological risk in the perioperative period 
and any statement of risks would be speculative.  Given this, we speculate that there could be 
psychological or emotional risk to patients in this study if they were to become aware of their cognitive 
decline more so than they would be if they were not participating in the study.  Patients will not be given 
the scores of their MoCA or CAM assessments, but if they were to become aware of a decline in their 
performance this could be stressful or disconcerting to the patient.  Additional counseling regarding any 
psychological or emotional distress stemming from this will be provided by the principal investigator at 
the request of the patient or family.  A second potential risk stems from possible dissemination of 
protected patient information. No identifiable health information will be exchanged between the Lumosity 
company and the investigators.  All PHI will be saved on password protected BIDMC research servers. 

(CCI) Committee on Clinical Investigations 
Page 8 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
 
Recruitment 
Eligible patients will be identified by operative scheduling lists, cardiac surgical clinic visit schedules, 
and pre-admission testing (PAT) clinic visit scheduling lists.  If the patient’s surgery is to be scheduled 
at least 10 days in advance from the day of their clinic visit, they will be approached by study staff for 
inclusion in the proposed study.    
 
Consent 
Once a patient is found eligible, he or she will be approached by a member of the study team for 
informed consent.  Informed consent will take place in the preoperative setting, either in cardiac surgery 
clinic or PAT clinic.  All subjects will be consented with curtains drawn or the door closed assuring 
patient privacy. The subjects will have the opportunity to ask any and all questions, and are free to 
decline participation at any time. Written informed consent will be obtained and copies provided to the 
patient and filed in the medical record. The patient may also be provided with an informational 
handout.  
 
Subject Protection 
Although patients of co-investigators may be approached for inclusion in this study, it will be clearly 
stated that the subjects’ decision to participate or refrain from participation in the research study will 
not affect the performance or outcome of their upcoming surgery.  Patients who cannot consent for 
themselves for reasons of a cognitive disability such as dementia will be excluded from this study. 
 
 
B7. 
STUDY LOCATION 
  
Privacy  
All study interactions and assessments will take place at BIDMC facilities.  For patients being 
approached for informed consent, if they are uncomfortable answering questions regarding their 
medical history with someone other than a medical provider than an approved MD participating in the 
study will be contacted to conduct that portion of the pre-enrollment interview.  Interactions and 
assessments will take place in private clinical settings with curtains/doors closed so as to provide 
privacy and comfort.  Family members will be asked to be present or leave for assessments at the 
patient’s request, so long as they do not interfere with study assessments via provision of answers or 
coaching.  For the follow up telephonic MoCA assessment the patient will be asked if they are 
comfortable providing answers to the questionnaire at that time.  If not, an appropriate time within the 
same day will be agreed upon between the patient and the study team member conducting the follow 
up assessment.       
 
Physical Setting 
Pre-enrollment screening and informed consent will take place in the BIDMC cardiac surgical or PAT 
clinics.  Assessments will take place in the cardiac surgery or PAT clinics, preoperative holding area 
and/or patient rooms.  Post-operative assessments at 1, 3, and 6 months will take place via 
telephone.  Return of study-related equipment (iPad tablets) will be coordinated with return visits for 
clinical care.     
 
 

(CCI) Committee on Clinical Investigations 
Page 9 of 9 
 
Study Description – Part B 
CCI Form:  9-2015 
 
PI Revision Date: 09/25/2017 
 
B8. 
DATA SECURITY 
All files, including those containing PHI, will be stored on a secure research server behind the BIDMC 
firewall on password protected computers and entered into a REDCap database; paper files will be 
stored in locked file cabinets/offices at BIDMC.  At enrollment, all patients will be given a unique, 
anonymized study user name and email address that will be used to track their participation in the 
Lumosity training program.  A log of this information will be kept only on BIDMC servers. Limited 
information will be retained on patients who are prescreened and do not qualify, or who are 
approached and declined, for the purposes of generating a CONSORT diagram at the conclusion of 
the trial.  Only final analysis produced from the REDCap database will be shared with the Lumosity 
company.   
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 
 
B10 
Dissemination of Research Results 
Patients will be thanked for their time throughout the study. There is no plan to share the data at the 
conclusion of the trial. Because study results are likely to be published a few years after a given 
subject’s participation, it is not feasible to send subjects follow-up with the published results. The 
study investigators are concerned that mailing the published manuscript and an additional thank-you 
note years after participation risks violating subject privacy, as mailing addresses are increasingly 
likely to change with passing time. It is out of the scope of this study to continue tracking mailing 
addresses after completion of enrollment since this is not a longitudinal study.