Preoperative and Postoperative Cognitive TrajEctories in oLdEr Patients With Deferred SURGEry Due to the COVID-19 Emergency: a Prospective Cohort Study
Conditions: Postoperative Cognitive Dysfunction, Depressive Symptoms, Postoperative Pain
Sponsor: McMaster University

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The Co-TELE-SURGE Study 
 
Preoperative and postoperative Cognitive TrajEctories in oLdEr patients with 
deferred SURGEry due to the COVID-19 emergency: 
a prospective cohort study  
 
Short title (max 25 characters): Deferred surgery @COVID19 
 
 
Protocol Version 3 
May 31, 2020 
 
 
 
 

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STUDY SUMMARY 
 
Title 
The Co-TELE-SURGE Study 
Preoperative and postoperative Cognitive TrajEctories in oLdEr patients with 
deferred SURGEry due to the COVID-19 emergency: a prospective cohort study 
Project Office 
Department of Health Research Methods, Evidence, and Impact 
McMaster University 
1280 Main St West, Hamilton, Ontario, Canada L8L 2X2 
Study Size 
330 patients 
Study Design 
Multicentre, prospective and longitudinal, cohort study 
Primary 
Objectives 
In older patients whose elective noncardiac surgery has been deferred because of 
the COVID-19 emergency, 1) to describe perioperative cognitive trajectories, and 
2) to explore the intra-individual changes in these trajectories from before to after 
surgery.  
Secondary 
Objectives 
In older patients whose elective noncardiac surgery has been deferred because of 
the COVID-19 emergency, 1) to describe the perioperative trajectories in 
depressive symptoms and pain, and 2) to explore their association with the 
trajectories in cognitive performance.  
Eligibility 
Criteria 
Inclusion criteria 
1. age 65 years or greater 
2. patient scheduled to perform noncardiac elective surgery expected to 
require at least an overnight stay in hospital after surgery 
3. surgery deferred, with a known or probable surgery date in ≥6 weeks  
4. informed consent provided 
Exclusion criteria 
1. patient undergoing cardiac surgery, or cranial surgery 
2. known history of dementia 
3. unavailability of tablet or computer with an internet connection for 
remote assessment 
4. patient unable to interact with a tablet or computer due to language, 
visual, or hearing impairment, or any severely limited mobility of the upper 
limb joints 
5. patient unable to understand spoken or written English 
6. surgery delayed for a intercurrent clinical event 
Follow-up and 
measurements
 At enrolment and monthly before surgery (i.e. ≥2 preoperative assessments per 
patient), and then 1 month, 3 months, 6 months, and 12 months after surgery, 
patients will be assessed remotely 
1. on their cognitive performance, through a computerized brief cognitive test 
battery, self-administered, i.e. the Cogstate Brief Battery (CBB) 
2. on their physical function/mobility, through the Function Component of the 
Late-Life Function and Disability Instrument (LLFDI-FC) and exploring life space 
mobility 

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3. on their depressive symptoms, through the short form (15-item) version of the 
Geriatric Depressive Scale (GDS) 
4. on their pain, through a Numeric Pain Rating Scale (NPRS) 
 
 

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Table of Contents 
1. BACKGROUND AND RATIONALE .................................................................................................. 5 
2. OBJECTIVES ......................................................................................................................................... 6 
3. METHODS ............................................................................................................................................ 6 
3.1 Study design................................................................................................................................................. 6 
3.2 Study population ........................................................................................................................................ 6 
3.2.1 Inclusion criteria ................................................................................................................................................ 7 
3.2.2 Exclusion criteria ............................................................................................................................................... 7 
3.3 Recruitment and procedures ................................................................................................................ 7 
3.4 Measurements ............................................................................................................................................ 8 
3.4.1 Cogstate Brief Battery (CBB) ......................................................................................................................... 8 
3.4.2 Changes in activities and participation since COVID-19 questionnaire ...................................... 9 
3.4.3 Late Life Function and Disability Instrument: Function Component (LLFDI-FC) ................... 9 
3.4.4 Geriatric Depression Scale (GDS) .............................................................................................................. 10 
3.4.5 Numeric Pain Rating Scale (NPRS) ........................................................................................................... 10 
3.5 Sample size ................................................................................................................................................ 10 
3.6 Data analysis plan................................................................................................................................... 11 
3.6.1 Primary analysis ............................................................................................................................................... 11 
3.6.2 Secondary Analyses ........................................................................................................................................ 12 
4. IMPORTANCE OF THE STUDY ..................................................................................................... 12 
APPENDIX I. Study timeline, measurements, and data collection ..................................... 14 
APPENDIX II. Performance at the Cogstate One-Back Task (OBK): interpretation and 
clinical relevance of changes in score .......................................................................................... 15 
APPENDIX III. Changes in activities and participation since COVID-19 questionnaire
 ................................................................................................................................................................... 16 
REFERENCES .......................................................................................................................................... 17 
 
 
 

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1. BACKGROUND AND RATIONALE 
The COVID-19 emergency has been impacting our patients and healthcare systems in 
several ways. To redeploy resources (staff and equipment) to priority areas, ensure hospital 
capacity to front the COVID-19 surge, and for infection control reasons, the use of operating 
rooms have been limited mainly to semi-urgent (e.g., oncology), urgent (e.g., hip fracture) and 
emergency (e.g., ruptured abdominal aortic aneurysm) surgeries, while many elective surgeries 
have been deferred to a later, often undermined, time. From a societal perspective, this is 
certainly thought to be the best choice in such an emergency. From an individual perspective 
this is going to represent a stressful situation for those patients, often older, whose surgery is 
not happening as planned.  
On the other side, from an epidemiological perspective, this represents a unique 
opportunity to study the impact of surgery on cognitive performance. Postoperative cognitive 
dysfunction (POCD) is an objectively measured decline in cognition postoperatively compared 
with preoperative function.1 2 The NeuroVISION study demonstrated that as many as 30% of 
patients aged 65 or older undergoing elective noncardiac surgery experience cognitive decline 
at 1 year after surgery, defined as ≥2 point decline in the Montreal Cognitive Assessment 
compared with before surgery.3 This has questioned the role of surgery in cognitive decline. 
Many of these patients have several comorbidities, which, in addition to age, could 
theoretically impact their cognitive performance over time. Therefore, it is still uncertain 
whether the decline we see in these patients who underwent surgery is different from what we 
would have seen if the same patients had not undergone surgery. An epidemiological study 
could try to answer this question comparing the surgical cohort with a matched non-surgical 
cohort. However, whatever matching approach we use, the control group is always going to be 
imperfect, and undoubtedly inferior to an approach that compares the individual with 
themselves. However, when we evaluate the effect of surgery comparing the patient cognitive 
performance at a certain time point after surgery with the cognitive performance measured at 
only one time point before surgery, we miss considering a possible pre-existing trend over time 
before surgery, which could hypothetically explain the change after surgery.  
While for some surgeries, a waiting time to surgery of months is not an unusual 
eventuality (e.g., some elective orthopaedic surgeries), this is a more unique circumstance for 
other major elective noncardiac surgeries. Therefore, to identify surgical candidates time 
before their surgery, and follow them up for a certain time before their surgery is often 
impracticable. Due to the COVID-19 contingency, we now have a sample of patients that, due to 
the deferral of their surgery we are capable of following and assessing for their cognitive status 
before they receive their surgery, for one to a few months. In this way, we will be able to draw 
preoperative individual-specific trajectories of cognitive performance, which represent an intra-
individual comparison to the postoperative cognitive performance, to evaluate the relative and 
absolute impact of surgery on our older patients. 
We expect that the COVID-19 pandemic, and the imposed social distancing, is having an 
impact on older patient lives, and also on older patients that are waiting for their surgery. 
Changes in their ability to live a normal life because of the current restrictions might translate 
into changes in their physical performance, and might have an impact on their mood and also 
on their perception of pain, and eventually translate into changes in their cognitive 
performance. The deferral of their surgery per se, and the possible adoption of adjuvant 

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therapies in the meantime, might have, at least theoretically, an influence on their overall 
performance. For all these reasons, we might see a different preoperative cognitive trajectory, 
compared with what we would have seen in a non-COVID-19 time. However, if surgery has an 
impact on our patient cognition, we still expect to see it as a postoperative change (e.g. a 
greater decline, a change in slope) compare to their actual preoperative trajectory, so that the 
performance we see at 3, 6 or 12 months after surgery is worse than what we would expect 
based on the preoperative trajectory.  
The use of computerized cognitive testing in older people has incredibly expanded in 
recent times. The existing literature confirms the strengths of this approach, which include 
standardization of administration and stimulus presentation, accurate measures of response, 
and efficiencies of staffing and cost, and supports feasibility and acceptability.4 5 Computerized 
testing allows also for remote cognitive assessment, which has been shown feasible and 
reliable also in older subjects, also with some cognitive impairment.6 7 In the era of physical and 
social distancing imposed by the COVID-19 emergency, this is particularly relevant. Moreover, 
since virtual and telecommunication tools have become a daily vehicle for maintaining some 
type of encounter with our patients, more older patients are becoming familiar with these 
types of encounters and tools.  
 
2. OBJECTIVES 
The primary objectives of our project are to describe perioperative cognitive trajectories 
of older patients whose elective noncardiac surgery has been deferred because of the COVID-
19 emergency, and explore the intra-individual changes in these trajectories from before to 
after surgery, through periodic remote self-administered cognitive testing.  
In the same study population, we will also have the following secondary objectives: 
 to describe the perioperative trajectories in mobility/physical function, depressive 
symptoms and pain, and explore their association with the trajectories in cognitive 
performance, before and after surgery; 
 to describe the change in activities and participation after the COVID-19 and social 
distancing started, in our study population, compared to a random sample of 
community-dwelling persons, 65 years old or older, in order to identify the additional 
impact of surgery deferral. We will pursue this secondary objective comparing our data 
with the results of an ongoing cross-sectional survey across community-dwelling older 
adults living in Greater Hamilton areas. 
 
3. METHODS 
3.1 Study design 
Our project is a multicentre, prospective and longitudinal, cohort study. 
3.2 Study population 
We expect to include 330 patients aged 65 years or older, scheduled for their 
noncardiac elective surgery whose surgery has been or will be deferred due to the slowdown of 
the operating rooms during the COVID-19 emergency at the Hamilton Health Science (HHS), St. 
Joseph's Healthcare Hamilton (SJHH), Woodstock General Hospital, London Health Sciences 

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Centre, Kingston General Hospital, Memorial University of Newfoundland, University of 
Saskatchewan, and University of Alberta.  
3.2.1 Inclusion criteria 
1. age 65 years or greater 
2. patient scheduled to perform noncardiac elective surgery expected to require at 
least an overnight stay in hospital after surgery 
3. surgery deferred, with a known or probable surgery date in ≥6 weeks  
4. informed consent provided 
3.2.2 Exclusion criteria 
1. patient undergoing cardiac surgery, cranial surgery 
2. known history of dementia 
3. unavailability of tablet or computer with an internet connection for remote 
assessment 
4. patient unable to interact with a tablet or computer due to language, visual, or 
hearing impairment, or any severely limited mobility of the upper limb joints 
5. patient unable to understand spoken or written English  
6. surgery delayed for an intercurrent clinical event 
3.3 Recruitment and procedures 
Eligible patients will be first approached by members of their circle of care. We have 
engaged surgeons from different disciplines at the participating sites. and we will distribute (via 
email) study information, including eligibility criteria, across surgical practices. The study team 
will be in periodic contact with surgical practices to look for potential participants. Members of 
the patient circle of care will ask the potential participants for permission to share their contact 
with the research team. The study will be then all conducted remotely, by videoconference 
(baseline) or telephone (follow-ups), with McMaster University as the coordinating and 
assessment centre. The study team will be in periodic contact with the participating surgical 
practices to look for potential participants. An informed verbal consent will be sought. After the 
first contact of the research team with the patient, an informative written document including 
the same information conveyed during the verbal consent process will be sent to the 
participant using the same email address that will be used during the study to deliver the link to 
the computerized tests. At the next call, once the patient has had a chance to review the 
document, the research personnel will look for confirmation of their consent to participate, 
before proceeding to any assessment. 
If the patient agrees to participate, the patient will be allowed, if necessary, to involve in 
the study a next of kin or support who can help facilitate the access to an electronic device with 
an internet connection which will be used to administer the cognitive battery remotely, and the 
training on the battery.  
The research team will set up an initial videoconference with the participant (and the 
next of kin/support if necessary) to explain the Cogstate Brief Battery (CBB), i.e. the internet-
based cognitive testing, and train on self-administration. Zero to 3 days before each scheduled 
cognitive assessment the participant  (or the next of kin/support) will be emailed a user-specific 

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link to the cognitive program. Around the same time the participant will receive a telephone 
call to remind to complete the assessment.  
The baseline videoconference-based visit with the patient will be conducted using 
different software options, as long as they allow screen sharing, including Skype and Zoom, 
based on availability and participant discretion. The subsequent calls will be done using the 
telephone. 
We will seek confirmation of consent to participate in the study during the initial 
videoconference, and at every telephone contact with the patient throughout the study.  
3.4 Measurements 
At the initial videoconference, data on baseline characteristics will be collected, 
including demographics, social history, comorbidities, and relevant pharmacological and non-
pharmacological (e.g. radiation) therapies. At the initial videoconference the questionnaire to 
explore change in activities and participation since COVID-19 will be also administered.  
At each of the calls that will remind the self-administered cognitive assessment, the 
research team member will also 
1) ask about any clinically relevant intercurrent event (i.e. hospital admissions, ED visits, 
visits to urgent care, changes in medications); 
2) assess mobility/physical function based on the Late Life Function and Disability 
Instrument: Function Component (LLFDI), and life space mobility questions 
3) assess depressive symptoms using the Geriatric Depression Scale (GDS) 
4) assess pain using a Numeric Pain Rating Scale (NPRS)  
Data on the participant past medical history, medication, date and type of surgery, 
postoperative course, and intercurrent clinical events will be obtained from the interview with 
participant, and confirmed or completed through review of electronic hospital medical records, 
based on the execution of a Data Transfer Agreement between McMaster University and 
Hamilton Health Sciences Corporation. If needed, for data completion or clarification, the 
participant’s family physician will be also contacted.  
APPENDIX I summarizes the study timeline and measurements. 
3.4.1 Cogstate Brief Battery (CBB) 
The Cogstate Brief Battery (https://www.cogstate.com) is a computer-based cognitive 
test extensively validated against standard neuropsychological batteries in cognitively normal 
older adults, as well as in patients with cognitive impairment, in the community and in different 
clinical contexts, both in a clinician/researcher-supervised manner, and in an unsupervised 
fashion (i.e., through an internet-based self-administration, at home). 8-10 It has been used also 
in the perioperative setting, showing equivalent or greater reliability, and greater sensitivity 
than conventional batteries.11 12 Moreover, In addition to proof of feasibility and acceptability 
even with older patients with some baseline cognitive impairment, its advantages are short 
duration (about 15 min), small practice effects (even with monthly assessments), and no ceiling 
effects.8 13 It consists of four tasks (Detection Task, Identification Task, Learning Task, and One-
Back Task) designed to assess psychomotor function, attention, working memory, and visual 
learning.13 Each task utilizes stimuli in the form of playing cards. Stimuli characteristics (e.g., 

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color, suit) are manipulated based on the requirements of each task. The primary performance 
measure for the Detection and Identification tasks is reaction time in milliseconds (speed), 
which is usually normalized using a logarithmic base 10 (log10) transformation. The primary 
performance measure for the Learning and One-Back tasks is the proportion of correct answers 
(accuracy), which is usually normalized using an arcsine square-root transformation. 
Based on industry web standards, the Cogstate system will communicate with the 
McMaster system through an Application Programming Interface (API), to generate user- and 
visit- specific links. The CBB will be host in a McMaster webpage, in a seamless fashion for the 
participant, who will be directed into the Cogstate application when they start the assessment, 
and then back to the hosting website upon completion of the tests. The CBB will present each 
cognitive test to the subject following a self-paced training test until valid cognitive data is 
provided, enabling testing without supervision. Subjects will receive a simple message at the 
end of their testing session indicating next steps. A detailed report with cognitive data will not 
be provided to subjects. For the purpose of this study, a support person will be allowed to 
attend the self-administration of the CBB. This will be established at the enrolment for each 
participant, and the participant will be instructed to self-administer the CBB under the same 
conditions at every assessment over time. 
After 1-5 days from the initial recruitment and training session, each participant will self-
administer the cognitive testing once, and then every month (i.e. 30 days, ±1 week) until their 
surgery is performed. We expect that each participant will have at least 2 assessments before 
surgery. Participants will then self-administer the CBB 1 month, 3 months, 6 months, and 12 
months after surgery. 
3.4.2 Changes in activities and participation since COVID-19 questionnaire  
Appendix III shows the questionnaire exploring changes in activities and participation since 
COVID-19. The questionnaire has been developed in the context of a survey study that is being 
conducted by investigators at the McMaster Institute for Research on Aging (MIRA) & Labarge 
Centre for Mobility in Aging (LCMA). In the MIRA/LMCA survey the questionnaire is 
administered, by telephone, to 500 community-dwelling older adults living in Greater Hamilton 
area, identified through random sampling based on census. In the Co-TELE-SURGE the 
questionnaire will be administered by the research personnel only once, i.e. at baseline, to 
collect data on the change in activities and participation experienced by the subject after the 
social distancing was imposed to face the COVID-19 pandemic, which, for the participants in our 
study temporally coincided with the change to their surgical plan. 
3.4.3 Late Life Function and Disability Instrument: Function Component (LLFDI-FC) 
The Function Component of the Late-Life Function and Disability Instrument (LLFDI-FC) is a 
widely used patient-reported outcome of physical function.14 15 It comprehensively assesses 
discrete functional tasks and operationalizes disability in important life roles beyond the narrow 
construct of activities of daily living. Extensive evidence supports its construct validity and 
sensitivity to change among various clinical populations of community-dwelling older adults.16 
The instrument will be administered over the phone by the research personnel at each follow-
up, preoperatively and postoperatively. Three additional questions will be also asked to explore 
life space mobility (being just outside the house, being in the neighborhood, and being outside 

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the neighborhood), which will also capture changes in social distancing policy that we expect 
will happen over the study period. At the end of the mobility questionnaire, the participants 
will be also asked whether there have been changes in their ability of performing basic and 
instrumental activities of daily living. 
3.4.4 Geriatric Depression Scale (GDS) 
The short form (15-item) version of the GDS17 is widely used instrument, which has 
demonstrated good reliability and validity in assessing depressive symptoms in older adults. 
The GDS Short Form takes an average of 5 to 7 min to complete and will be administered by the 
research personnel on the phone. 
3.4.5 Numeric Pain Rating Scale (NPRS) 
 
The Numerical Pain Rating Scale (NPRS) is a rapid subjective measure of pain in which 
individuals rate their pain on an eleven-point numerical scale. The scale is composed of 0 (no 
pain at all) to 10 (worst imaginable pain). Correlation with other pain-assessment tools and 
feasibility of its use also in telephone interviews, have been demonstrated.18 The NPRS will be 
administered by the research personnel on the phone. 
3.5 Sample size 
The slowdown of the operating rooms due to COVID-19 started in mid-March, and it will 
last at least until the end of June or July at the participating sites. We expect to recruit 330 
participants between May and August 2020. This sample size will be sufficient to test our 
primary hypothesis that, on average, in our population, the cognitive performance at 6 months 
after surgery will be worse, in a clinically significant way, compared to what we would expect 
based on the preoperative trajectory. We will base our primary hypothesis on the performance 
at the One-Back Task (OBK) of the CBB, at 6 months after surgery. The OBK assesses working 
memory, which is a cognitive domain often found altered in the context of postoperative 
cognitive dysfunction. It uses a well-validated n-back paradigm with stimuli from playing cards. 
The subject is asked whether the card displayed in the center of the screen is the same as the 
card presented immediately before. The subject responds by pressing the “yes” or “no” key. 
The primary outcome variable for this test is accuracy of correct response, normalized using an 
arcsine square-root transformation. In APPENDIX II we provide a table summarizing the clinical 
relevance of the test and its results, with data on the difference in performance between 
healthy older adults, and older adults with mild cognitive impairment (MCI) or dementia based 
on standardized neuropsychological assessment.13 19 Based on the literature, a typical score of 
healthy older adults is 1.35; the average difference, at one time point, in the OBK score, 
between healthy older adults and older adults with mild cognitive impairment (MCI), and older 
adults with dementia, is, respectively, 0.07 and 0.17.13 19 We hypothesize that in our study 
population we will see a preoperative trajectory, which, if it continued, unchanged, after 
surgery (Ho), would lead to an average decrease in OBK score of 0.009 over 6 months. This is 
still consistent with a decline over time compared with what we would expect on average in a 
healthy older population.13 19 Our hypothesis (H1) is that surgery will change the preoperative 
trajectory so that at 6 months after surgery we will instead see an average decrease, compared 
with right before surgery, of 0.035 (which would correspond to the average change in a 
hypothetical population in which 40% of subjects experience a decline of at least 0.07, 50% no 

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change, and 10% an improvement of 0.07). Based on a test of comparison of means in one 
sample, with an alpha error of 0.05 (2-tailed), and a standard deviation for the OBK score of 
0.16,13 to enrol 330 subjects will be sufficient to test our hypothesis with 80% of power, even in 
case of an attrition rate as high as 10%.  
Recruiting 330 participants is a feasible goal based on the current status of knowledge 
about the COVID-19 contingency plan. The lockdown of the operating rooms started in March 
and will last at least until the end of June, or longer, depending on the participating site. During 
the lockdown, we expect to be able to enroll at least 120 participants at McMaster sites, and 
30-50 participants at each of the other participating sites. Even when the operating rooms will 
reopen to more elective surgeries in the next months, this will happen slowly, so that we expect 
a carryover of the lockdown at least until the end of the summer. Moreover, it is projected that, 
if countries increase their normal surgical volume by 20% post-pandemic, it would take a 
median 45 weeks to clear the backlog of operations resulting from COVID-19 disruption.20 
Therefore should we see a recruitment rate slower than expected, for any reason, we will 
extend our recruitment period to beyond the summer.  
3.6 Data analysis plan 
Using descriptive statistics, we will present demographic and clinical baseline 
characteristics of our study population. 
3.6.1 Primary analysis 
We will report descriptive summary statistics of the performance of the study 
population at each of the 4 CBB tasks for each of the preoperative and postoperative time 
points. We will also represent individual and averaged performance trajectories graphically.   
To explore whether surgery has a statistically significant impact on cognitive 
performance and its trajectories, we will model data using interrupted time series analyses. 
Interrupted time series analysis is a powerful quasi-experimental design to study the 
longitudinal effects of interventions or exposures, accounting for pre-intervention/pre-
exposure trends. We will adopt the approach described in Kontopantelis et al., BMJ 2015.21 22 
According to this approach we will use regression models in which the within patient 
performance variation over time is partitioned into three main components, to provide 
independent tests for the slope in scores in the pre-operative period (test 1); the change in 
level (i.e., absolute change) around surgery, allowing for the trend before surgery (test 2); and 
the change in slope from before to after surgery (test 3).21 22 The preoperative slope quantifies 
the trend in performance before surgery. The level change is an estimate of the absolute 
change in cognitive performance that can be attributed to surgery, i.e., between the time 
points immediately before and immediately after surgery, and accounting for the preoperative 
trend. The change in slope quantifies the difference between the preoperative and 
postoperative slope. Based on the hypothesis that the postoperative trajectory will not be 
homogenous over the 12 months after surgery, we will also adopt a more complex interrupted 
time series model that will allow for different slopes of change in different time segments, i.e. 
right before to 1 month after surgery, 1-3 months, 3-6 months, and 6-12 months after 
surgery.23 We will conduct the primary analysis first considering only the early-intermediate 
postoperative performance (up to 6 months after surgery). With the assumption that the 

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impact of surgery can last as long as one year,2 we will repeat the analysis including also the 
change between 6 and 12 months after surgery. In our regression models, we will use estimates 
of error variance obtained from bootstrap techniques using 1000 bootstrap samples.We will 
analyze the performance at each task separately, and then combining the 4 scores into one 
unique measure of performance. We will explore whether clinically significant changes have 
occurred at any time point. There is no standard definition for what is a clinically significant 
perioperative decline across different tests.24 25 In addition to the change as defined in our 
sample size calculation (i.e. a change in score equal to or greater than the average difference in 
scores between a healthy older adult and a subject with MCI), we will consider also 2 most 
commonly adopted definitions, i.e. 1) a change of ≥20% in test scores,26 and 2) a reliable change 
index (RCI) of ≥1.65. The RCI is an index commonly used in neuropsychology,27 and also in 
studies using the CBB,13 calculated by dividing the individual’s test-retest difference score by 
the standard error of that difference score, and can be interpreted as a standard Z score. The 
cut-off of RCI=1.65 is the point beyond which 5% of the values from the normal sample 
population will fall (i.e. P<0.05, one tailed test). We will compare the performance scores at 
each time point with the preceding time points, and evaluate the changes based upon these 
criteria. We will provide the number and percentage of patients experiencing a cognitive 
decline based on these definitions at each of the segments of the observation period. We will 
also compare our study population data with existing age-stratified normative data for the 
CBB.28 
In our primary analyses, we will include only patients who completed ≥2 assessments 
preoperatively and ≥3 assessments (i.e. 1, 3, and 6 months) postoperatively. Secondarily, we 
will repeat our analysis dealing with missing data 1) through multiple imputation techniques; 
and 2) using a method of evidence-informed data imputation, previously implemented in our 
studies, which takes onto account the reason for the missing data.3 
3.6.2 Secondary Analyses 
We will explore whether the effect of surgery on cognitive trajectories differ based on 
baseline patient characteristics, including age, type of surgery, cognitive performance at 
baseline, comorbidities, mobility, GDS and pain score. This will be done studying the interaction 
of these covariates with the components of the interrupted time analysis. The interrupted time 
series approach as described assumes linearity and constancy of the preoperative trend when 
projected postoperatively. We will evaluate the validity of these assumptions exploring the 
association of changes in cognitive performance with intercurrent events other than the index 
surgery, for the long-term effects. 
With a similar approach as for the cognitive performance, we will study the 
perioperative trajectories of patient physical function/mobility (as indicated by the LLFDI-FC 
and the life space mobility questions), depressive symptoms (as indicated by the GDS), and of 
pain (as indicated by the NPRS). We will also explore whether the time-dependent LLFDI-FC, 
GDS and NPRS scores are associated with the time-dependent cognitive scores. 
 
STATA software, version 15, will be used for the analyses. 
 
4. IMPORTANCE OF THE STUDY 

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Capitalizing on one of the unfortunate consequences of the COVID-19 emergency, i.e. the 
deferral of many elective surgeries, our study will provide a unique insight into the role of 
surgery on perioperative and postoperative cognitive trajectories in older patients. At the same 
time, the study will enlighten on trajectories of patient reported outcomes, such as mobility, 
mood, and pain, in patients waiting for their delayed surgery in the COVID-19 era.  
Our study will be also a proof of concept for a perioperative study design, which could 
be applied to a larger scale, and to other perioperative outcomes. 
Finally, as an unintended positive consequence, this study will translate into a periodic 
tele-contact with older patients who, during and after the COVID-19 pandemic, will most suffer 
the consequences of the social distancing. 

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APPENDIX I. Study timeline, measurements, and data collection 
 
Before surgery 
After surgery 
Measurement 
- ≥6 
weeks 
Monthly 
+1 mo 
+3 mo 
+6 mo 
+12 mo 
 
Videoco
nference 
with 
research 
team 
Reminder 
call with 
research 
team* 
Patient 
self-
admini
stered 
Reminder 
call with 
research 
team* 
Patient 
self-
administ
ered 
Reminder 
call with 
research 
team* 
Patient 
self-
administ
ered 
Reminder 
call with 
research 
team* 
Patient 
self-
administ
ered 
Reminder 
call with 
research 
team* 
Patient 
self-
administ
ered 
Verbal consent 
(confirmation) 
x 
x 
 
x 
 
x 
 
x 
 
x 
 
Sociodemographic 
and clinical data 
x 
 
 
 
 
 
 
 
 
 
 
Intercurrent clinical 
events** 
 
x 
 
x 
 
x 
 
x 
 
x 
 
Information on 
index surgery  
 
 
 
x 
 
 
 
 
 
 
 
Cogstate Brief 
Battery (CBB) 
 
 
x 
 
x 
 
x 
 
x 
 
x 
Change in activities 
and participation 
due to COVID-19 
x 
 
 
 
 
 
 
 
 
 
 
Late-Life Function 
and Disability 
Instrument (LLFDI-
FC) and life space 
mobility 
 
x 
 
x 
 
x 
 
x 
 
x 
 
Geriatric Depression 
Scale (GDS) 
 
x 
 
x 
 
x 
 
x 
 
x 
 
Numeric Pain Rating 
Scale (NPRS) 
 
x 
 
x 
 
x 
 
x 
 
x 
 
*0-3 days before the expected self-administered cognitive assessment 
**hospital admissions, ED visits, visits to urgent care, changes in medications

Version 3.0 May 31, 2020 - Page 15 of 19 
 
APPENDIX II. Performance at the Cogstate One-Back Task (OBK): interpretation and 
clinical relevance of changes in score 
 
From Lim 201313 and Mackin 201819 
Baseline score (SD) 
in HA 
Average 
difference in 
score between HA 
and persons with 
MCI at any time 
point 
(Cohen’s d) 
Average difference 
in score between 
HA and persons 
with dementia at 
any time point 
(Cohen’s d) 
Score change per 
every additional 
year of age 
(population level) 
1.35 (0.16) 
0.07 
(0.60) 
0.17 
(2.40) 
-0.004 
HA – healthy older adults 
MCI - subjects with mild cognitive impairment 
 
 

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APPENDIX III. Changes in activities and participation since COVID-19 questionnaire 
In the next set of questions, we will ask you about how your perceived functional ability and 
daily activities have changed since social distancing began due to COVID-19. You can reply by the 
following 5-point scale: much worse, a little bit worse, stayed about the same, a little bit better, 
much better. 
Activities 
Much 
Worse 
A little 
bit 
worse 
About 
the 
same 
A little 
better 
Much 
better 
Your ability to move around in your home (such as 
walking, climbing stairs) become … 
  
  
  
  
  
Your ability to engage in sports or recreational 
activity (such as casual/brisk walking, dancing, 
bowling, shuffleboard, hiking, Yoga, gymnastics, 
stationary bike,) become … 
  
  
  
  
  
Your ability to engage in housework activity (such 
as dusting, washing dishes, and vacuuming) 
become … 
 
 
 
 
 
Your ability to stay physically active (walking, 
exercise, working out) become.. 
  
  
  
  
  
Participation 
Much 
Worse 
A little 
bit 
worse 
About 
the 
same 
A little 
better 
Much 
better 
Since social distancing began due to COVID-19 has 
… 
  
  
  
  
  
Your ability to keep in touch with others (through 
letters, cell phone/phone or email) become … 
  
  
  
  
  
Your ability to take care of your health (such as 
managing daily medications, following a diet, 
cooking your own meals, bathing, dressing and 
toileting) become … 
  
  
  
  
  
Your ability to take care of your errands (such as 
buying groceries or taking care of finances) 
become … 
  
  
  
  
  
Your ability to participate in the community and 
maintain a social life (e.g., volunteer, go to church, 
meet with others) become… 
 
 
 
 

Version 3.0 May 31, 2020 - Page 17 of 19 
 
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