A Single-center, Observational, Longitudinal Study on the Effect of Slow Wave Sleep (SWS) Characteristics and Race and Ethnicity on Amyloid Burden (a Marker of Alzheimer's Disease Risk), Among Cognitively Normal Elderly
Conditions: Alzheimer Disease
Sponsor: NYU Langone Health

 
 
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Version 
Number 
Version Date 
Summary of Revisions Made 
1.0 
18 September 2018 
Original version 
2.0 
12 December 2018 
First Modification 
 
 

 
 
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A SINGLE-CENTER, OBSERVATIONAL, LONGITUDINAL STUDY 
ON THE EFFECT OF SLOW WAVE SLEEP (SWS) 
CHARACTERISTICS AND RACE AND ETHNICITY ON AMYLOID 
BURDEN (A MARKER OF ALZHEIMER’S DISEASE RISK), 
AMONG COGNITIVELY NORMAL ELDERLY 
 
 
 
Principal Investigator: 
 
Ricardo Osorio, MD 
Department of Psychiatry 
NYU Center for Brain Health 
145 E 32nd St. 
New York, NY 10016  
(212) 263-3255 
Additional 
Investigators: 
 
Girardin Jean-Louis, PhD 
Department of Population Health 
NYU Center for Healthful Behavior Change 
180 Madison, 7th floorNew York, NY 10016 
(646) 501-2623 
NYULMC Study 
Number: 
s18-01302 
Funding Sponsor:  
NIH/NIA 
ClinicalTrials.gov 
Number                 
In preparation 
 
Initial version: 9.18.2018 
 

Study #: s18-01302 
 
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Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the Protection of 
Human Subjects (45 CFR Part 46), any other applicable US government research regulations, and 
institutional research policies and procedures. The Drs. Osorio and Jean-Louis assure that no deviation 
from, or changes to the protocol will take place without prior agreement from the sponsor and documented 
approval from the Institutional Review Board (IRB), except where necessary to eliminate an immediate 
hazard(s) to the study participants. All personnel involved in the conduct of this study have completed 
Human Subjects Protection Training. 
 
 

Study #: s18-01302 
 
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Table of Contents 
 
PROTOCOL SUMMARY .........................................................................................................1 
SCHEMATIC OF STUDY DESIGN ......................................................................................... 3 
1 
KEY ROLES ................................................................................................................... 4 
2 
INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ..... 5 
2.1 
BACKGROUND INFORMATION AND RELEVANT LITERATURE .................................................................. 5 
2.2 
RATIONALE .......................................................................................................................................... 6 
2.3 
POTENTIAL RISKS & BENEFITS ............................................................................................................. 7 
2.3.1 
Known Potential Risks ................................................................................................................. 7 
2.3.2 
Known Potential Benefits .......................................................................................................... 10 
3 
OBJECTIVES AND PURPOSE ..................................................................................... 10 
3.1 
PRIMARY OBJECTIVE.......................................................................................................................... 10 
3.2 
SECONDARY OBJECTIVES (IF APPLICABLE) .......................................................................................... 10 
4 
STUDY DESIGN AND ENDPOINTS ........................... ERROR! BOOKMARK NOT DEFINED. 
4.1 
DESCRIPTION OF STUDY DESIGN ............................................... ERROR! BOOKMARK NOT DEFINED. 
5 
STUDY ENROLLMENT AND WITHDRAWAL ............................................................. 10 
5.1 
INCLUSION CRITERIA ......................................................................................................................... 12 
5.2 
EXCLUSION CRITERIA ........................................................................................................................ 12 
5.3 
VULNERABLE SUBJECTS ..................................................................................................................... 13 
5.4 
STRATEGIES FOR RECRUITMENT AND RETENTION .............................................................................. 13 
5.4.1 
Use of DataCore/Epic Information for Recruitment PurposesError! 
Bookmark 
not 
defined. 
5.5 
DURATION OF STUDY PARTICIPATION ................................................................................................ 13 
5.6 
TOTAL NUMBER OF PARTICIPANTS AND SITES .................................................................................... 13 
5.7 
PARTICIPANT WITHDRAWAL OR TERMINATION .................................................................................. 14 
5.7.1 
Reasons for Withdrawal or Termination ................................................................................. 14 
5.7.2 
Handling of Participant Withdrawals or Termination .......................................................... 14 
5.7.3 
Premature Termination or Suspension of Study ..................................................................... 14 
6 
STUDY SCHEDULE ...................................................................................................... 15 
6.1 
SCREENING ........................................................................................................................................ 15 
6.2 
ENROLLMENT/BASELINE ................................................................................................................... 15 
6.3 
INTERMEDIATE VISITS .............................................................. ERROR! BOOKMARK NOT DEFINED. 
6.4 
FINAL STUDY VISIT ................................................................... ERROR! BOOKMARK NOT DEFINED. 
6.5 
WITHDRAWAL VISIT .......................................................................................................................... 17 
6.6 
UNSCHEDULED VISIT ......................................................................................................................... 17 
7 
STUDY PROCEDURES/EVALUATIONS ....................................................................... 17 
7.1 
PROCEDURES/EVALUATIONS ............................................................................................................. 17 
7.2 
LABORATORY PROCEDURES/EVALUATIONS ....................................................................................... 20 
7.3 
STUDY SPECIFIC BIOSPECIMENS ........................................................................................................ 20 
7.3.1 
Specimen Collection Procedures .............................................................................................. 20 
7.3.2 
Specimen Preparation, Handling, and Storage ..................................................................... 20 
7.3.3 
Specimen Shipment .................................................................................................................... 21 
7.4 
QUESTIONNAIRE ADMINISTRATION .................................................................................................... 21 
7.5 ................................................................................................................................................................... 21 
8 
SAFETY AND ADVERSE EVENTS ................................................................................ 21 
8.1 
DEFINITIONS ..................................................................................................................................... 21 
8.2 
RECORDING OF ADVERSE EVENTS ...................................................................................................... 23 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS .................................... 23 

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8.3.1 
Investigator reporting: notifying the IRB ................................................................................ 23 
9 
STUDY OVERSIGHT ................................................................................................... 24 
10 
STATISTICAL CONSIDERATIONS .............................................................................. 25 
10.1 
STUDY HYPOTHESES .......................................................................................................................... 25 
10.2 
SAMPLE SIZE DETERMINATION .......................................................................................................... 25 
10.3 
STATISTICAL METHODS ...................................................................................................................... 25 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS ................... 26 
12 
ETHICS/PROTECTION OF HUMAN SUBJECTS .......................................................... 27 
12.1 
ETHICAL STANDARD .......................................................................................................................... 27 
12.2 
INSTITUTIONAL REVIEW BOARD ........................................................................................................ 27 
12.3 
INFORMED CONSENT PROCESS ........................................................................................................... 27 
12.3.1 
Consent/Assent and Other Informational Documents Provided to Participants ............. 27 
12.3.2 
Consent Procedures and Documentation............................................................................. 27 
12.4 
PARTICIPANT AND DATA CONFIDENTIALITY .......................................................................................28 
12.4.1 
Research Use of Stored Human Samples, Specimens, or Data .......................................... 29 
12.5 
FUTURE USE OF STORED SPECIMENS ................................................................................................. 29 
13 
DATA HANDLING AND RECORD KEEPING ............................................................... 29 
13.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES ............................................................... 30 
13.2 
STUDY RECORDS RETENTION ............................................................................................................ 30 
13.3 
PROTOCOL DEVIATIONS .................................................................................................................... 30 
13.4 
PUBLICATION AND DATA SHARING POLICY ........................................................................................ 30 
14 
STUDY FINANCES ....................................................................................................... 31 
14.1 
FUNDING SOURCE .............................................................................................................................. 31 
14.2 
COSTS TO THE PARTICIPANT ............................................................................................................... 31 
14.3 
PARTICIPANT REIMBURSEMENTS OR PAYMENTS ................................................................................ 31 
15 
STUDY ADMINISTRATION .......................................................................................... 31 
15.1 
STUDY LEADERSHIP ........................................................................................................................... 31 
16 
CONFLICT OF INTEREST POLICY ............................................................................... 31 
17 
REFERENCES ............................................................................................................. 32 
18 
ATTACHMENTS .......................................................................................................... 32 
 
 
 

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List of Abbreviations 
 
 
%AF 
African Ancestry 
AA 
African American 
AC 
Attenuation Correction 
ADC 
Alzheimer’s Disease Center 
AE 
Adverse Event/Adverse Experience 
ADPiBmask 
AD-vulnerable ROIs PiB SUVR values 
AD 
Alzheimer’s Disease 
Aβ 
Amyloid Beta 
AHI4% 
Apnea Hypopnea Index with 4% desaturation 
BEDTIME 
Brain Sleep Deprivation MRI Effects 
BMI 
Body Mass Index 
CAB 
Community Advisory Board 
CBI 
Center for Biomedical Imaging  
CBO 
Community Based  
CSF 
Cerebrospinal Fluid 
CVD 
Cardiovascular disease 
CVE 
Cardiovascular events 
CRF 
Case Report Form 
CBH 
Center for Brain Health 
CDR 
Clinical Dementia Rating 
CHBC 
Center for Healthful Behavior Change 
CNS 
Central Nervous System 
CT 
Completion Time  
DKI 
Diffusion Kurtosis Imaging 
EKG 
Electrocardiogram  
FU 
follow-up 
FDA 
Food and Drug Administration 
FLAIR 
Fluid-attenuated Inversion Recovery 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ISF 
Interstitial Fluid  
IRB 
Institutional Review Board 
MoCA 
Montreal Cognitive Assessment 
MRI 
Magnetic Resonance Imaging 

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MCI 
Mild Cognitive Impairment 
mPFC 
medial Prefrontal Cortex 
n 
Number  
MSISC 
Mount Sinai Integrative Sleep Center 
NACC 
National Alzheimer's Coordinating Center 
NCRAD 
National Cell Repository for Alzheimer’s Disease 
NIH 
National Institutes of Health 
NIA 
National Institute on Aging 
NREM 
Non-REM 
NYULMC 
NYU Langone Medical Center 
NPSG 
Nocturnal Polysomnography 
OSA 
Obstructive Sleep Apnea 
PS 
Plasma Serum 
PET 
Positron Emission Tomography 
PCP 
Primary Care Physician 
PI 
Principal Investigator 
PHI 
Protected Health Information 
PiB 
Pittsburgh Compound B 
RDI 
Respiratory Disturbance Index  
SNR 
Signal to Noise Ratio 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SWA 
Slow Wave Activity 
SWS 
Slow Wave Sleep 
ROI 
Region of Interest 
SUVR 
Standard Uptake Value Ratio 
TST 
Total Sleep Time 
UTE 
Ultrashort Echo Time 
US 
United States 
UDS 
Uniform Data Set  
WASO 
Wake After Sleep Onset 
WHR 
Waist to Hip Ratio 
WML 
White Matter Lesions 
 
 

Study #: s18-01302 
 
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Protocol Summary 
Title 
A SINGLE-CENTER, OBSERVATIONAL, LONGITUDINAL STUDY 
ON THE EFFECT OF SLOW WAVE SLEEP (SWS) 
CHARACTERISTICS, RACE AND ETHNICITY ON AMYLOID 
BURDEN (A MARKER OF ALZHEIMER’S DISEASE RISK), AMONG 
COGNITIVELY NORMAL ELDERLY  
 
Short Title 
The Sleep Amyloid, Slow WAve Race and Ethnicity  (Sleep AWARE) study 
Brief Summary 
African-Americans (AAs) have an increased prevalence of both Alzheimer’s 
disease (AD) and vascular risk factors for AD such as diabetes and hypertension 
when compared to whites. However, in a recent community based study of non-
demented elderly, black race was associated with higher amyloid burden 
after adjusting for vascular risk factors, suggesting the presence of additional 
physiological differences on AD-risk by race in the early stages of the disease. 
The purpose of this study is to test whether poor slow wave sleep (SWS) 
quantity (SWS duration) and quality (slow wave activity, SWA) is one of these 
physiological factors. To test these hypotheses, we will perform community 
outreach in barbershops, churches and senior centers in Brooklyn and other 
NYC boroughs with which we have created substantial ties in recent years. In 
consultation with community stakeholders, we will recruit 150 cognitively 
normal AA elderly (age 60-75) and 60 age, sex, BMI, income and education 
matched non-Hispanic whites from the same geographical areas. We will first 
perform a medical and cognitive evaluation (Visit 1). Participants will then 
undergo 2 nights of home sleep monitoring using an unattended device to 
exclude OSA, followed by 7 days of actigraphy with a sleep log to record sleep 
duration. Both devices will be returned by mail. Subjects with reported total 
sleep time (TST) between 5 and 10 hours and absence of moderate to severe 
OSA will be invited to perform a 2-night nocturnal polysomnography (NPSG) 
(Nights 1-2) and a PiB-PET MR scan (Visit 2).   
Objectives 
Objective 1: To test if African ancestry (%AF) is associated with short SWS 
duration and poor SWA in older AAs. 
Objective 2: To test the effect of race and its interaction with baseline short 
SWS duration/poor SWA on longitudinal amyloid deposition. 
Objective 3: To test the effect of race and baseline poor SWA on cognition. 
Secondary Objective 2.1: To test whether loss of sleep-dependent spatial 
navigational memory at baseline is a predictor of cognitive decline.  
 
Methodology 
30-36 month longitudinal study 
Endpoint 
Primary endpoint is longitudinal increase in amyloid deposition 
 
Study Duration 
5 years 
Participant 
Duration 
30-36 months 

Study #: s18-01302 
 
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Population 
210 cognitively normal elderly (Clinical Dementia Rating [CDR]=0), self-
identified as African-American (AA) or non-Hispanic white (NHW), ages 60 to 
75 years, with English as their primary language. The reason for only including 
native English speakers is due to the nature of the study and cognition being 
one of the outcomes of the study. The reason for including only African 
American blacks and NHW is the focus of this grant which is on African 
Americans and their African genetic ancestry and admixture. Based on our 
preliminary data an existing literature, in order for genetic admixture analyses 
to be applied rigorously, the control group needs to be of NHW. The definition 
of NHW are people in the United States who are considered racially white and 
are not of Hispanophone identity or the Hispanosphere (terms used to refer to 
Spanish-language speakers and the Spanish-speaking world as compared to for 
example English-speaking of French-speaking to name a few). Other non-
English non-Hispanic white ethnicities will not be invited to participate due to 
the lack of adequate neuropsyschological tools and testers proficient in other 
native European languages and the confounding effects of immigration.  These 
NHW participants will be located within the same zip codes as the AAs. 
Study Sites 
NYU locations: 
the Center for Brain Health (CBH) at NYULMC,  
the Center for Biomedical Imaging (CBI), NYU Langone Health, 
Department of Radiology, 660 1st Avenue  
 
External Site: 
the Mount Sinai Integrative Sleep Center (MSISC) (New York, NY) 
 
 
 
 
Number of 
participants 
210 participants expected to be enrolled with 150 cognitively normal African-
American elderly and 60 non-Hispanic white. 
Statistical Analysis 
We will incorporate standard techniques such as omnibus tests and 
appropriate adjustments to significance (α) levels (e.g., Bonferroni correction) 
for post-hoc contrasts to control for multiple comparisons. Both selection and 
attrition biases might occur. Appropriate techniques (e.g., Heckman 2-stage 
approach (GEE Probit Model) and Monte Carlo (EM algorithm) will be used to 
address biases or missing data. Since only two time points will be analyzed, we 
will use linear regression models with the annual rate of amyloid change as 
dependent variable. Significance will be defined by p<.05 where p will be 
Bonferroni corrected when testing post-hoc contrasts. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study #: s18-01302 
 
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Schematic of Study Design 
 
 
 

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1 Key Roles 
 
Primary Site: NYU School of Medicine 
Ricardo Osorio Suarez, M.D,  
Assistant Professor  
Department of Psychiatry (PI) 
NYU School of Medicine 
(212) 263-3255 
Ricardo.Osorio@nyulangone.org 
 
Girardin Jean-Louis, PhD, 
Professor 
Department of Population Health (PI) 
Department of Psychiatry 
NYU Center for Healthful Behavior Change 
(646) 501-2623 
Girardin.Jean-Louis@nyulangone.org 
 
External Site: Mt. Sinai School of Medicine 
Indu Ayappa, Ph.D, 
Associate Professor  
Department of Medicine (Sub-contract PI) 
Icahn School of Medicine at Mount Sinai  
(212) 241-1967 
indu.ayappa@mssm.edu 
 
David Rapoport, M.D,  
Professor 
Department of Medicine (Co-Investigator) 
Icahn School of Medicine at Mount Sinai  
(212) 481-1818 
david.rapoport@mssm.edu 
 
Andrew Varga, M.D and Ph.D,  
Assistant Professor 
Department of Medicine (Co-Investigator) 
Icahn School of Medicine at Mount Sinai  
(212) 241-6084 
andrew.varga@mssm.edu 
 
Collaborator: Columbia University Medical Center (Analysis of de-identified datasets only) 
Giuseppe Tosto, MD, PhD 
Assistant Professor  
Department of Neurology 
Columbia University Medical Center 
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain 
(212) 305-9274 
Gt2260@columbia.edu 
 
Danurys Sanchez 
Senior Research Staff Associate  
Columbia University Medical Center 
Department of Neurology 
G.H. Sergievsky Center and 
The Taub Institute 
 (212)-342-3055  

Study #: s18-01302 
 
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dls167@cumc.columbia.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 Introduction, Background Information and Scientific 
Rationale 
2.1 Background Information and Relevant Literature 
Sleep duration in America has gradually declined over the last four decades, with current average sleep 
duration being of approximately 6 hours18. Parallel to this decline, African Americans (AAs) have the 

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highest prevalence of long (≥9 h) and short sleep (≤6 h)61-63, within the intervals commonly associated with 
morbidity and increased AD-risk68-70. AAs take longer to fall asleep18-23, have lower sleep efficiency and have 
consistently shown to spend a smaller proportion of time in deep stages of non-REM (NREM) (also called 
slow wave sleep [SWS])19;20;23-28;32.  Possible mediators underlying these racial differences in sleep include 
age, sex, obesity, psychosocial factors, health care behaviors and medical disorders21;23;27;71-76. A meta-
analysis designed to estimate the magnitude of these variations in sleep, showed that racial/ethnic 
differences in sleep duration and continuity were moderated by the factors underlined above23, while only 
psychosocial stressors (measured as perceived discrimination)20;21;26 were partially associated with the 
decreases in SWS duration, suggesting that race still remained an important independent risk factor for 
decreased SWS among AAs. A recent study confirmed this finding showing that decreased SWS duration 
was associated with an increased percentage of African ancestry (%AF)39 even after adjusting for several 
demographic, socioeconomic and clinical covariates. Further replication is warranted, but African ancestry 
has also been associated to increased risk for hypertension77 and diabetes78 both of which have been linked 
with reductions in time spent in SWS79;80.  
 
Approximately 20% of healthy adults have mild and 6.6% moderate-to-severe obstructive sleep apnea 
(OSA)81, with a higher incidence occurring in the elderly82. AAs generally show a higher prevalence of OSA33-
36. Specifically, in the Cleveland Family Study, AAs presented with OSA at a younger age35, while Ancoli-
Israel et al.34 found that older AAs were 2.5 times more likely to have severe OSA. These findings are in 
agreement with another study of adults aged 40-60, where OSA rates were higher among minorities33. In 
contrast, both the Sleep Heart Health (7% AAs) and Scharf’s et al. studies failed to show higher rates of OSA 
in AAs after controlling for obesity83;84. However, AAs from these studies suffered more excessive daytime 
sleepiness, in agreement to previous findings suggesting that OSA-associated symptoms might be more 
common in AAs34;85. Apnea occurs less commonly during SWS, as SWS is associated with a higher 
respiratory arousal threshold86;87 and more stable breathing88. However, beyond a certain threshold of 
frequency, apnea in any sleep stage impairs entry into SWS. In addition, the temporal course of slow wave 
activity (SWA) has shown to be slower in mild OSA89, and severe OSA patients show up to a 40% rebound 
in SWS duration during treatment with CPAP90. All the above findings suggest that changes in SWS are 
common in OSA patients. SWS disruption may therefore be another mechanism by which OSA increases 
AD risk91-93.  
In summary: certain ethnic groups are more likely to have disturbed sleep. AAs show clear 
independent differences in SWS characteristics but not in sleep duration or OSA prevalence when compared 
to whites, after controlling for socioeconomic factors, obesity or health care behaviors. These differences 
seem unrelated to other explanatory factors (expect for the partial effect of psychosocial stressors) and 
suggest that AAs may have less restorative sleep than whites.  The brain consequences of these decreases in 
SWS are not known. 
 
2.2 Rationale 
 
Primary Aims. To examine: i) whether African Ancestry (%AF) is associated with decreased SWS duration 
and SWA; ii) the effects of race on longitudinal amyloid build-up and its interaction with baseline SWS 
duration and SWA in cognitively normal elderly; iii) the effects of race and its interaction with baseline SWA 
on longitudinal changes in global cognition, memory, executive function and a spatial navigational memory 
task.  Exploratory aim. We will test whether loss of sleep-dependent spatial navigational memory at baseline 
is a predictor of cognitive decline at follow-up. 
 
Rationale for ethnicity/nativity and clinical groups selection: 
Multiethnic cohort studies provide better information about disease causation but they are expensive to 
design. We will focus on 150 African-American (AA) blacks since African or Caribbean-born are not equally 
admixed and inclusion of more ethnic groups would result in loss of power for Aim 1 and need for great 
increases in sample size. As a comparison group, we will include 60 matched non-Hispanic whites. Race 
will be represented both as binary (self-identified AA vs. self-identified white) and numeric (% of African 
ancestry). Irregular sleep-wake rhythms and extreme sleep durations may also increase AD risk68-70. The 
study will not formally test these sleep disorders, as these subjects are hard to recruit in community-based 

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studies (often reluctant to participate in studies that monitor sleep) and the focus is on SWS. Insomnia will 
be allowed as long as total sleep time (TST) is between 5-9 hours based on actigraphy recordings and sleep 
logs performed at home. 
 
2.3 Potential Risks & Benefits 
2.3.1 Known Potential Risks 
The following risks and discomforts may be experienced during participation in the study. In spite of all 
precautions, medical complications may occur. These include not only physical injury, but also possible 
psychological, social or economic harm, discomfort or inconvenience, or breach of confidentiality.  To 
minimize risks, all study personnel are highly trained and experienced; materials are kept in locked file 
cabinets and are only available to investigators and research personnel associated with the study. All 
materials sent to outside laboratories are anonymized and the codes are kept with the NYU CBH Contact-
PI (Dr. Osorio, MD). Both NYU’s CBH and the Center for Healthful Behavior Change (CHBC), which will 
be a collaborator on this study to help provide expertise in recruitment strategies, have excellent records of 
safekeeping patients’ data and have never had a breach of security. In the event of an adverse event at NYU 
or MSISC there are medical personnel available. 
 
1. Physical, Neurological and Psychiatric Exams: 
For the standard clinical examinations, there are minimal to no risks associated with the testing. The 
main risk is a loss of privacy and every precaution is taken to ensure confidentiality. Other psychological 
risks include discovering a condition that was not previously known. 
 
2. Psychometric Testing: 
There are no risks associated with cognitive testing. Some individuals may experience fatigue or test 
performance anxiety.  Periodic breaks will be available during cognitive testing.   
 
3. Laboratory Analysis of Blood: 
The potential risks of blood drawing may occasionally include pain, bruising, fainting, or a small 
infection at the puncture site. Sometimes a small amount of bleeding into the arm (hematoma) may occur. 
 
4. Heart Tracing (EKG): 
The back of the electrodes are adhesive and may be uncomfortable when they are removed.  There are 
no other risks associated with an EKG other than discovering a heart condition that was not previously 
known. 
 
5. Genotyping: 
There are potential dangers in obtaining DNA information. Genetic testing can generate information 
about a subject’s personal health risks and can cause or increase anxiety, damage family relationships, 
and/or compromise insurability, employability and lead to social discrimination. To greatly reduce the 
possibility of such psychological or social risks, genetic results will be coded and no personal identification 
will link the subject with the genotype. Genetic results will not be disclosed to participants. We will include 
recommended language about the certificate of confidentiality and its limitations to the consent form. 
 
6. MRI Scan: 
 MRI scanning involves the use of powerful magnets delivering radio frequency energy. Therefore, 
patients who have implanted metal devices, such as pacemakers, certain aneurysm clips, or shrapnel or 
metal in the eye, skull or elsewhere in the body are at risk. There are no known risks or adverse effects 
resulting directly from exposure to magnetic fields and radio frequency energy used in this study. Contrast 
agents are not used in this study. Some people feel claustrophobic in the MR or PET-MR scanners. The MR 
scanner produces loud tapping sounds during operation and earplugs are provided to all subjects. Other 
rare risks of MRI may include neuro-stimulation effects resulting in muscle twitches and tingling 
sensations, due to the rapid switching of magnetic fields, and a slight increase in body temperature that 
may occur in the presence and absorption of radio frequency energy. These are, however, very unlikely 
under current operational guidelines.  In the very remote event that the magnet loses its magnetism, liquid 

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helium in the magnet will be released. The room is designed with ventilation systems to prevent 
accumulation of these gases. 
   
7. 11C-Pittsburgh compound-B (PiB) PET-MR scan: 
 
There is the possibility of discomforts associated with venous catheters. These risks include: minor pain 
or soreness, lightheadedness and/or minor bruising at the site of the catheter insertions, and less 
commonly, the formation of a small clot or swelling of the vein and bleeding. A chance of infection also 
exists. Experienced medical personnel will be involved in venipuncture procedure to minimize the possible 
risks associated with the catheters.  As the effective dose (ED) of PiB is about 2.93 mSv when the 
recommended activity of 412 MBq of PiB is administered, adverse reactions due to radiation are expected 
to occur with a very low probability. In addition, PET/MR eliminates the exposure to CT scans used for 
attenuation correction by the PET/CT systems, so the radiation included would be lower than that of a 
similar study using PET/CT. Critical organ gallbladder wall exposure is 23.03 mGy.  PiB  is an experimental 
substance and other individual responses are possible and cannot be predicted.  The frequency of allergic 
reactions to PiB is not known.   
 
8. Sleep Studies: 
The in-laboratory NPSG sleep studies are identical to those performed in clinical practice and present 
almost no risks as we will be using the standard diagnostic protocol for all subjects presenting to the MSISC 
with sleep complaints meriting a sleep study. The sleep study has no risks beyond the minor irritation that 
attachment of the recording electrodes on the skin occasionally may cause.  
 
D.  ADEQUACY OF PROTECTION AGAINST RISKS:  
 
1. Recruitment, Informed Consent and Incidental Findings: 
This study will involve male and female African-American elderly and white volunteer subjects with a 
diagnosis of ‘cognitively normal’ (CDR=0).  Informed consent is obtained from each subject using IRB 
approved consent forms. In the consent form and in discussion with an investigator, participants will be 
advised fully of the procedures to be used, the amount of time required of them, the possible risks and 
benefits of the procedures, their right to refuse participation in the study without prejudice, their right to 
terminate participation at any moment without prejudice, and the name and telephone number of the 
Principal Investigators (Drs. Osorio and Jean-Louis). In the informed consent form (ICF), participants will 
be told that the information they provide and all findings will be kept strictly confidential, with access 
limited to the research staff and the possible exception of state or federal regulatory personnel. Several steps 
will be taken to minimize reactions of discomfort, embarrassment, fatigue, or boredom. 
 
Interviews will be conducted by staff that are well trained and closely supervised by Ferdinand Zizi. The 
informed consent procedure explains the overall purpose of the study in straightforward terms, and 
explains the conditions of confidentiality. We encourage participants’ questions and comments throughout 
the interview. For our questions about educational and cultural background, we emphasize that there is ‘no 
right answer’ to the questions. All participants are informed that they may refuse to answer any question 
and that they may discontinue the interview at any time without affecting their participation in the study 
or medical treatment. Participants are explicitly asked for their feedback, reactions, and strategies. 
Research staff that conduct follow-up interviews are blind to prior research diagnosis. All personnel of the 
study will have successfully completed the required education on protection of human research participants 
performed at NYU Langone Medical Center (NYULMC). In the ICF and in the discussion with members of 
the research team, participants will be advised that if the standard medical, neurological, or 
neuropsychological evaluation should uncover significant deficit or an emergent and previously 
undiagnosed medical condition, or if the blood assays reveal significantly abnormal findings, Dr. Butler will 
contact the participant to discuss the condition and, if permitted, contact the participant’s physician or refer 
the  participant to an appropriate medical professional for follow-up. A technician reviews each MRI scan 
as they are being acquired for major abnormalities. A licensed, board-certified radiologist will perform a 
safety review on every MRI scan and results will be communicated to study participants within 4 weeks of 
the date they are obtained. Findings of clinical significance, such as a mass, acute hemorrhage/infarct will 
trigger telephone notification of the subject by Dr. Tracy Butler, MD and will inform them that an abnormal 
result has been found, and instructing them to contact their primary care physician (PCP). In addition, with 

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permission, their PCP will be contacted and a report from the neuroradiologist will be sent to that physician. 
In the absence of clinically significant findings, the report of the neuroradiology review will be 
communicated to the participant in the form of a letter that describes the general findings; a more detailed 
radiological report is transmitted to the participant’s PCP upon explicit request and retained in a permanent 
data base, but no direct telephone contact will be made. If the subject has no physician, and has a clinically 
significant finding, we will arrange for follow-up care at a local clinic.  
 
2. Protection Against Risk: 
 
a. PiB PET scans  
 
PET-MR scanning involves the use of powerful magnets. Therefore, patients who have implanted metal 
devices, such as pacemakers, certain aneurysm clips, or shrapnel or metal in the eye, skull or elsewhere in 
the body are at risk. There are no known risks or adverse effects resulting directly from exposure to magnetic 
fields and radio frequency energy used in this study. Contrast agents are not used in this study. Some people 
feel claustrophobic in the PET-MR scanners. The MR scanner produces loud tapping sounds during 
operation and earplugs are provided to all subjects. Other rare risks of MRI may include neuro-stimulation 
effects resulting in muscle twitches and tingling sensations, due to the rapid switching of magnetic fields, 
and a slight increase in body temperature. These are, however, very unlikely under current operational 
guidelines.  In the very remote event that the magnet loses its magnetism, liquid helium in the magnet will 
be released. The room is designed with ventilation systems to prevent accumulation of these gases. 
 
Amyloid Pittsburgh compound B (PiB) tracer: 
There is no recommended dose for PiB. 300 MBq is the lowest dose that has 
been recommended in the human studies published thus far (Klunk WE, Ann 
Neurol. 2004 Mar;55(3):306-19; Scheinin NM J Nucl Med. 2007 Jan;48(1):128-
33), but most studies published to date include doses from 370 to 555 MBq (for a 
Cochrane review see Zhang S, Cochrane Database of Systematic Reviews 2014, 
Issue 7), with 370 MBq being the lowest injected dose below which the scan 
‘should not be performed and be rescheduled’ according to the PET Technical 
procedures ADNI methods published in May 10th 2007 Version 1.2 
(http://www.adniinfo.org/Scientists/doc/PET_PIB_Tech_Procedures_Manual_Suppl_v1.3.pdf) Given the:  
i) heterogeneity in injected doses; ii) the heterogeneity in the current conduct and interpretation of the 
tests; iii) the lack of defined thresholds for determination of test positivity; iv) the plan of sharing the scans 
from this study with both the ADNI LONI Image Data Archive (IDA) and NACC Imaging; and; v) in the low 
signal to noise ratio (SNR) with 412 MBq injections in the first scans performed at NYU we have decided to 
follow ADNI methods and inject 555 MBq of PiB to increase the quality of the signal and the  external 
validity of our findings, as well as future use of the data by outside groups  
 
b. Clinical Studies and Labs 
There are minimal physical risks associated with the standard diagnostic procedures. Moreover, there 
are minimal psychological risks to patients who participate in this study.  
 
c. Sleep Studies 
The in-laboratory sleep studies are identical to those performed in clinical practice. The sleep study has 
no risks beyond the minor irritation that attachment of the recording electrodes on the skin occasionally 
may cause. There is the possibility that sleep might be disrupted by the fact that subjects will be sleeping in 
a new environment. All data will be coded and  stripped of identifiers to protect the confidentiality of the 
subjects. All sleep analyses and in-labs will be performed within the MSISC (11 East 26th Street). MSISC 
has explicit emergency and procedure guidelines in place for dealing with medical emergencies that may 
arise.  
 
Figure 1. PiB PET Scan 

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2.3.2 Known Potential Benefits 
Participants are made aware that the study does not provide clinical treatment and should not be used 
as a substitute for proper medical care with a physician; however, if the standard medical, neurological, or 
neuropsychological evaluation reveals significant deficit or an emergent and previously undiagnosed 
medical condition, or if the blood assays, or MRI scan reveal significant abnormalities, this information will 
be discussed with the participant and transmitted to their PCP. We do not expect the majority of 
participants to benefit directly from the research other than by financial remuneration for their time and 
effort. The potential benefits to society are considerable if this study reveals new information about new 
biological mechanism of AD risk in African-American elderly. Therefore, the risks to participants are 
reasonable in relation to the anticipated benefits to society. 
 
3 Objectives and Purpose 
3.1 Primary Objective 
Aim 1 will test if African ancestry (%AF) is associated with short SWS duration and poor 
SWA in older AAs. Challenge: AAs consistently spend less time in SWS than whites23-32. Although SWS 
shows significant heritability, social stressors may moderate these differences. Approach: test whether 
%AF40  is associated with SWS characteristics after controlling for psychosocial factors (e.g. stress related 
to ethnicity). Outcome: positive results would suggest that racial differences in SWS have genetic 
underpinnings. 
 
Aim 2 will test the effect of race and its interaction with baseline short SWS duration/poor 
SWA on longitudinal amyloid deposition. Challenge: AAs spend less time in SWS23-32, a sleep stage 
important for Aβ dynamics41-43 that may confer protection against amyloid deposition44. Approach: assess 
how race is associated with longitudinal PiB uptake and its interaction with short SWS duration and poor 
SWA, after controlling for: 1) medial prefrontal (mPFC) atrophy, TST, AHI4% and cerebrovascular damage 
(measured as white matter lesion [WML] volume and abnormal diffusion kurtosis imaging [DKI] indices); 
and, 2) psychosocial factors, health care behaviors and medical morbidity. Outcome: reduced SWS/SWA 
would become a novel risk factor for AD in African Americans (AAs). 
 
Aim 3 will test the effect of race and baseline poor SWA on cognition. Challenge:  race and poor 
sleep have been associated with cognitive impairment. However, most studies are confounded by the 
inclusion of OSA patients, subjective measurements of sleep, lack of valid cognitive assessments for AAs 
and inadequate enrollment of minorities. Approach: we will test for the association between race and 
longitudinal changes in global cognition, memory, executive function and a sleep-dependent spatial 
navigational memory task. In addition, we will test their interaction with baseline SWA, using a similar 
approach as in Aim 2. Outcome: positive results would emphasize the importance of health messages 
promoting good sleep hygiene among AA elderly.  
3.2 Secondary Objectives (if applicable) 
 
Secondary Objective : Exploratory: we will test whether loss of sleep-dependent spatial navigational 
memory at baseline is a predictor of cognitive decline at follow-up. A linked objective is to identify how 
the relationship between SWS/SWA and the rate of change in PiB uptake might be confounded by mPFC 
atrophy (for measures of SWS) and DWML volumes and DKI (for measures of PiB uptake). 
 
4 Study Enrollment and Withdrawal 
 
Subjects: 
210 cognitively normal, ages 60-75, self-identified as African-American (150) or non-Hispanic white 

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(60), Clinical Dementia Rating (CDR) of 0, ≥-1.25 in global cognition z-scores from the WHICAP battery 
adjusted for race and education, English speakers, and with enough literacy to provide voluntary consent 
will be invited to participate.  
 
Exclusion criteria at enrollment will be: intention to move from NYC within the same year, irregular sleep-
wake cycles defined as ‘≥3 sleep episodes per 24-hr period’ or ‘day to day irregularity greater than 90 min. 
based on actigraphy, less than 5 or more than 10 hours of TST; OSA (defined as AHI4%>15 and AHI4%>5 
with Epworth≥10); neurodegenerative disorders, history of early onset familial AD; insulin dependent 
diabetes; bipolar disorder, schizophrenia, intellectual disability or substance abuse; non-controlled 
pulmonary or cardiac diseases; brain tumors; stroke; head trauma and hydrocephalus.  
 
Lifelong depression and anxiety will be allowed as long as there has been no active depressive episode within 
the last two years. Current use of any sedative/hypnotics or stimulants, gabapentin, pregabalin, tricyclic 
antidepressants, and trazodone or other psychoactive medications that may alter SWS. Stable (3 months or 
longer) use of antidepressants will be allowed. Caribbean or African-born blacks or subjects that don’t fulfill 
inclusion criteria but express interest will be offered participation in similar NYU NIH-funded studies on 
sleep or normal aging.  
 
Study Enrollment: 
Self-identified AA and whites will be balanced by sex, age, BMI, income and education, and will live in 
the same NYC zip codes. Brooklyn will be the area of recruitment as it is the most ethnically diverse and 
largest most concentrated black population in the US -more than 900,000 blacks living in a 4-mile square 
area-. The sample will include self-identified African-American (AA) blacks and non-Hispanic whites. As 
described in our published methods158;166, enrollment sites will include advertisements and collaborations 
with black-owned barbershops, beauty salons and churches that were part of our previous community 
studies in Brooklyn and other NYC boroughs. All advertisements and recruitment materials will be 
submitted for IRB approval prior to use. In addition, we will perform culturally-relevant educational events 
in senior centers and church health fairs.  Recruitment will be implemented in consultation with a 
Community Activist (Ms. Aird) and a Community Advisory Board (CAB) that has been created for this 
cohort. It will include community stakeholders with whom we have long-standing relationships and consist 
of: black community leaders serving as Directors of Community-based organizations (CBOs) and members 
of the Brooklyn chapter of CaringKind. The CAB will comprise 8 members and will meet with the PIs and 
Dr. Galvin, who will be one of the lead members of the community advisory board every 2 months during 
year 1 and every 3 months thereafter. Once the award is made, it will discuss project goals, review 
recruitment strategies, refer individuals for participation and suggest new recruitment sites that might not 
have been available previously. Our success in assessing sleep in AAs is attributable to our sustained 
engagement efforts at the community level and help from former CABs.   
Participating recruitment sites will be selected based on visibility, accessibility, safety, longevity and 
cooperativeness204. Preference will be accorded to those providing private room for interactions with 
subjects. Recruitment procedures will be discussed with site owners before scheduled visits. Respective 
owners will introduce the recruitment team, who will then approach potential participants (while waiting 
at the salon, after church services or senior center activities) to describe the protocol. The recruitment team 
will be made up of research coordinators and other members of the study staff. As in our previous 
interventions158, staff will begin by exchanging pleasantries with potential participants followed by an 
introduction to the study.  
 
If interested, eligibility will be confirmed and consent obtained. They will then complete the Center for 
Epidemiologic Studies Depression (CES-D)205 Scale,  the Medical Outcomes Study Short Form (MOSSF)206, 
the ARES-TM questionnaire149, a medication list and the AD8207 (these forms will be used for initial 
screening; interested subjects not eligible or with high risk for OSA will be offered participation in similar 
NYU NIH-funded studies). Those refusing to enroll will receive standard sleep literature and access to the 
NYU ADC Center or Brooklyn’s NYU affiliated Lutheran Medical Center. No further contact will be made. 
During the first 9 months, themes derived from focus groups (R01MD004113) and through meetings 
between the PIs, Dr. Galvin and the CAB will be used to develop sleep and memory health booklets using 
Taylor’s model208. These booklets will be left on the participating centers for recruitment outside the 
scheduled visits. All recruitment materials will be submitted to the IRB through a modification for approval 

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before use.  
4.1 Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
Male and female subjects with normal cognition and ages 60 to 75. 
 
Within normal limits on neurological and psychiatric examinations. All subjects enrolled will have both 
a CDR=0,  a MoCA > 25 and ≥-1.25 in global cognition z-scores from the WHICAP battery. 
 
An informed family member or life-partner (preferably bed-partner) will be interviewed over the phone 
or on the first or second visit to confirm the reliability of the subject interview.  A study partner is 
preferably a spouse, close friend, or relative. 
 
Self-identified as African-American Black or non-Hispanic white. 
 
All subjects must sign the Alzheimer’s Disease Center consent form 
 
 
4.2 Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, 
hydrocephalus, seizures, mental retardation or other serious neurological disorder (e.g. Parkinson’s 
disease or other movement disorders). Subjects with a Fazekas scale >2 will be excluded260. 
 
Significant history of alcoholism based off of the CAGE questionnaire (>2) or drug abuse. 
 
History of psychiatric illness (e.g., schizophrenia, bipolar or PTSD 
 
Lifelong depression and anxiety will be allowed as long as there has been no active depressive episode 
within the last two years. 
 
Geriatric Depression Scale212 (short form)>6.  
 
Insulin dependent diabetes. 
 
Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions based off of 
the PI’s discretion.  
 
Physical impairment of such severity as to adversely affect the validity of psychological testing. 
 
Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging. 
 
Medications affecting cognition or SWS: 
o 
Narcotic analgesics. 
o 
Chronic use of medications with anticholinergic activity. 
o 
Anti-Parkinsonian medications (carbidopa/levodopa, amantadine, bromocriptine, pergolide, 
selegiline).  
o 
Others: amphetamines, amphetamine-like compounds, appetite suppressants, phenothiazines, 
reserpine, buspirone, clonidine, disulfiram, guanethidine, MAO inhibitors, theophylline, 
tricyclic antidepressants, gabapentin, pregabalin, trazodone, cholinesterase inhibitors, 
memantine. 
 
Chronic use of antidepressants are allowed.  
 
History of a first-degree family member with early onset (age <60 years) dementia.  
 
Irregular sleep-wake rhythms (based on participant self-report), short sleepers (< 5 hours a day) and 
long sleepers (> 10 hours a day). 
 
OSA (defined as AHI4%>15 and AHI4%>5 with Epworth≥10) 
 
Self-identified as US-born Caribbean Black, Caribbean-born Black or African-born Black. 
 
Diagnostic Criteria: 
 
1. The diagnoses of MCI, and AD.  All subjects get extensive baseline and follow-up evaluations to 
identify co-morbidity and any confounding medical, neurological, and psychiatric conditions that can affect 
cognition. For all subjects, the study neurologist or psychiatrist administers a standardized interview of a 
knowledgeable informant. The diagnosis is assigned at consensus case conferences using established and 
reliable procedures. The following diagnoses might be given at follow-up: 
 

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b. The definition of MCI: subjects demonstrating functional complaints (self-reported and supported by 
a knowledgeable informant) and who on clinical interviews show no dementia but with a CDR=0.5, GDS 
=3, and MOCA <25 are classified as MCI. Amnestic (a) aMCI is defined on the basis of updated. Petersen 
criteria with delayed recall performance below 1.5 SD from age norms on 2 of the 3 tests within the delayed 
recall domain. Prior experience shows that the aMCI will likely also show deficits in other cognitive 
domains. The category of non-aMCI is defined based on performance on more than one cognitive test from 
a domain other than delayed recall, falling below z=1.5 SD from the norms (see below). Subjects judged to 
be cognitively impaired by the clinician, but with a presentation, tests, symptoms and clinical evaluation 
that is not consistent with MCI will be classified as ‘Impaired, not MCI’. 
 
c. The diagnosis of AD: at the follow-up is consistent with the NINCDS-ADRDA workgroup 
recommendations and DSM IV criteria. The definition of AD requires that after ruling out other dementia 
etiologies that the individual demonstrate on structured clinical interviews, progressive impairments in two 
or more areas of cognition and difficulties in activities of daily living. Thus AD is rated as CDR >0.5. The 
memory impairment criterion is satisfied by scores in the impaired range on any of the delayed recall tests 
in the neuropsychological battery. Functional impairment is estimated by scores on the Lawton Brody 
Activities of Daily Living Scale, the clinical history evaluation, and the informant interview. 
 
4.3 Vulnerable Subjects 
 
 
We are not including children or women who are pregnant because this study is designed for adults and 
elderly subjects. 
4.4 Strategies for Recruitment and Retention 
Expected Participant Flow:  
Yearly complete evaluations (including baseline and follow-up) will range from 80-84 (Table 2). Initial 
screening will be performed through the CES-D, MOSSF, ARES-TM, medication list and AD8. The number 
of total subjects enrolled will be of 270 to meet the goal of 210 eligible subjects. We anticipate that 17% will 
be referred to seek treatment due to OSA, while 3-5% will not complete the study evaluations or fulfill 
inclusion criteria due to cognitive impairment. Based on an average of 24 hours of contact time for each 
subject (6 h for visits 1-2, 18 h for night 1-2) we will be able to complete 2 subjects per week. To maximize 
cohort retention we will adopt strategies developed for our own studies209-211 and more than 20 years of 
experience working with underrepresented groups at the NYU ADC. These will include: i) a multicultural 
staff; ii) providing flexible visit options; iii) using monetary incentives after completion of all study visits 
(each subject will receive $500 after a completed milestone and payment is not contingent upon completing 
all visits); iv) making reminder phone calls prior to scheduled visits; v) providing a clinical report to share 
with their primary care physician; vi) sending Annual Holiday letters; vii) performing telephone follow-ups 
after completion of the baseline visit; and, viii) participating in local memory walks in Brooklyn together with 
the Alzheimer’s Association, and co-sponsoring together with the NYU ADC three annual scientific updates 
at NYU’s Langone Medical Center in both English and Spanish. Previous annual attrition rates at the ADC 
have been 4% for healthy controls, 13% for MCI and 20% for AD patients. We anticipate that the efforts 
described above will lead to even higher retention rates (expected 95% at the 2.5 year follow-up) 
 
4.5 Duration of Study Participation 
The study will be over the course of 30 months per participant, although we will provide flexible visit 
options and up to 35 months will be allowed.  
4.6 Total Number of Participants and Sites  
 
Up to 270 people will be enrolled to reach a goal of 210 evaluable participants (accounting 
for attrition). 

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4.7 Participant Withdrawal or Termination 
4.7.1 Reasons for Withdrawal or Termination 
Participants are free to withdraw from participation in the study at any time upon request.  An 
investigator may terminate participation in the study if: 
 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant. 
 
The participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation during the 2-year follow-up.  
 
4.7.2 Handling of Participant Withdrawals or Termination 
 
For a variety of reasons, subjects may decide to withdraw from the study, or the PI may decide to 
terminate a subject’s participation regardless of whether the subject wishes to continue participating.  Data 
collected on the subject to the point of withdrawal will remain part of the study database and will not be 
removed. The consent document will give the subject the option of having his/her data anonymized. In all 
cases we will ask subjects who are withdrawing whether they wish to provide continued clinical follow-up 
subsequent to their withdrawal (i.e. yearly clinical interview by Dr. Butler and neuropsychological 
evaluations that are part of the UDS-3). Under this circumstance, the discussion with the subject will 
distinguish between study-related evaluations and continued follow-up of associated clinical outcome 
information, such as medical course obtained through a clinical interview and neuropsychological tests. A 
second option will be to continue participation through the ADC cohort. In all cases we will address the 
maintenance of privacy and confidentiality of the subject's information. 
 
If a subject: i) withdraws from the study, ii) does not consent to continued follow-up of associated clinical 
outcome information, and iii) does not request removal of their data, the PI will not access for purposes 
related to the study the subject’s medical record or other confidential records requiring the subject’s 
consent. However, the PI may review study data related to the subject collected prior to the subject’s 
withdrawal from the study, and may consult public records, such as those establishing survival status. A 
subject will be considered lost to follow-up after non-response to: 5-10 phone calls to the telephone number 
provided by the subject, 5 phone calls to the study partner, 3 emails and 1 certified letter to the participant 
home address. Replacement will be allowed in those subjects that withdraw from the study in less than 12 
months after the baseline visit. 
 
4.7.3 Premature Termination or Suspension of Study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to the investigator, funding agency, and regulatory authorities. If the study 
is prematurely terminated or suspended, the PI will promptly inform the IRB and will provide the reason(s) 
for the termination or suspension. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete and/or evaluable 
 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
satisfy the sponsor and/or IRB. 

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5 Study Schedule 
5.1 Screening 
Screening Visit (Day 0)  
 
Obtain verbal consent from potential participants.  
 
Fill out the following forms: Center for Epidemiologic Studies Depression Scale (CES-D), Medical 
Outcomes Study Short Form (MOSSF), ARES-TM Questionnaire 
 
Review medical history to determine eligibility based on inclusion/exclusion criteria. 
 
Review medications history to determine eligibility based on inclusion/exclusion criteria. 
 
Schedule study visits for individuals who are eligible and available for the duration of the study.   
 
Provide potential participants with instructions needed to prepare for first study visit  
5.2 Enrollment/Baseline 
 
Enrollment/Baseline Visit 1 (Visit 1, Day 1) 
This visit will occur at the Center for Brain Health (CBH) 145  E. 32nd Street, 2nd Floor 
 
Obtain and document consent from participant on study informed consent form (ICF). 
 
Obtain demographic information, medical history, medication history, alcohol and tobacco use 
history.  
 
Clinical evaluation and record results of physical examinations 
 
Collect blood and urine for clinical labs and in order to obtain ApoE genotyping 
 
Perform EKG 
 
Administration of the clinical section of the UDS 3.0 cognitive evaluation 
 
Administration of the WHICAP cognitive battery 
 
Verify inclusion/exclusion criteria after clinical interview, clinical labs and neuropsychological 
tests.   
 
Participants will receive a one week sleep diary, WatchPAT to wear for 1 night and an actigraph to 
wear during the remaining 7 days of the week. 
 
Baseline Visit 3 (Visit 2, Night 1/Day 2) 
 
This visit will occur at the Mount Sinai Integrative Sleep Center (MSISC) 11 E 26th Street, 13th Floor  
 
Nocturnal Polysomnography at their usual bedtime 
 
Provide actigraphy device to monitor naps and compliance with the instruction to not sleep 
between visits while at home. 
 
Provide breakfast. 
 
Subjects can go home for the day. 
 
Baseline Visit 4 (Visit 3, Night 2/Day 3) 
This visit will occur at the Mount Sinai Integrative Sleep Center (MSISC) 11 E 26th Street, 13th Floor 
 
 
Virtual maze spatial navigational memory test training session. 
 
Nocturnal Polysomnography. 
 
Virtual maze spatial navigational memory test testing session. 
 
Provide breakfast 
 
Baseline Visit 5 (Visit 4, Day 4) 
 
This visit will occur at the Center for Brain Health and the Center for Biomedical Imaging (660 
1st Avenue at E. 38th Street) Complete UDS 3.0 Cognitive evaluation and sleep interview  at the 
Center for Brain Health 

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 
PiB PET-MR Scan: PiB PET-MR scan of your brain at the Center for Biomedical Imaging 
(Pregnancy urine test will be done on women prior to the exam) 
o 
PET/MR scans combine two types of imaging methods: Positron Emissions Tomography 
(PET) and Magnetic Resonance Imaging (MRI).  PET uses radioactive tracers to produce 
images that can inform us how a particular compound is used by tissue or for identifying 
unique cell-types, such as Tau, in this study.  MRI uses magnetic fields and radio waves to 
produce images that can inform us about structures and function of tissue in the body. 
Combining both techniques provides more useful information while reducing the amount 
of radiation exposure compared to a standard PET scan or PET/CT. A small amount of 
tracer known as 11C-Pittsburgh compound-B (PiB) will be injected into a vein in your arm 
before the scan begins and a 60-min PET-MR scan will be performed 35 min after injection. 
Followup Study Visit 
 
12-Month Follow-Up Visit 1-day visit 
This visit will occur at the Alzheimer’s disease Center  (ADC) 145  E. 32nd Street, 2nd Floor 
 
UDS 3.0 cognitive evaluation will be re-administered by Alzheimer’s Disease Center clinicians and 
testers 
 
You will have a physical, neurological, and psychiatric examination along with collection of vital 
signs (heart rate, blood pressure, temperature, and breathing rate) and medical history including 
medications you take and surgeries you have had. 
 
Electrocardiogram (EKG): Assesses the electrical activity of your heart.  Electrodes (sensors 
connected to wires on the EKG machine) will be attached to your chest, upper arms, and legs. The 
heart tracing will take approximately 10 minutes to complete. 
 
You will have a urinalysis for routine testing to screen for urinary infections.  
Blood will be drawn for clinical labs and to obtain DNA for ApoE genotyping (Baseline Visit 1 only). 
The total amount of blood to be donated for the baseline and follow-up visits up the study is 
equivalent to approximately 6 tablespoons of blood. 
No MRIs or additional procedures will be perfomed in the 12 month fu visit 
 
30-month Follow-Up Visit 1 (Visit 1, Day 1) 
This visit will occur at the Center for Brain Health (CBH) 145  E. 32nd Street, 2nd Floor 
 
Obtain demographic information, medical history, medication history, alcohol and tobacco use 
history 
 
Clinical evaluation and record results of physical examinations 
 
Collect blood for clinical labs  
 
Perform EKG 
 
Administration of the clinical section of the UDS 3.0 cognitive evaluation 
 
Administration of the WHICAP cognitive battery 
 
Verify inclusion/exclusion criteria after clinical interview, clinical labs and neuropsychological tests 
 
Participants will receive a one week sleep diary, and an actigraph to wear during the week. 
 
30-month Follow-Up Visit 2 (Visit 2, Night 1) 
This visit will occur at the Mount Sinai Integrative Sleep Center (MSISC) 11 E 26th Street, 13th Floor 
 
Nocturnal Polysomnography at their usual bedtime 
 
Provide actigraphy device to monitor naps and compliance with the instruction to not sleep 
between visits while at home. 
 
Provide breakfast. 
 
Subjects can go home for the day. 
 
30-month Follow-Up Visit 3 (Visit 3, Night 2/Day 3) 
This visit will occur at the Mount Sinai Integrative Sleep Center (MSISC) 11 E 26th Street, 13th Floor 
 
Virtual maze spatial navigational memory test training session. 
 
Nocturnal Polysomnography. 
 
Virtual maze spatial navigational memory test testing session. 

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 
Provide breakfast. 
 
30-month Follow-Up Visit 4 (Visit 4/ Day 4) This visit will occur at the Center for Brain Health and 
the Center for Biomedical Imaging (660 1st Avenue at E. 38th Street) Complete UDS 3.0 Cognitive 
evaluation and sleep interview at the Center for Brain Health 
 
Complete UDS 3.0 Cognitive evaluation  
 
PiB PET-MR Scan 
5.3 Withdrawal Visit 
For a variety of reasons, subjects may decide to withdraw from the study, or the PI may decide to 
terminate a subject’s participation regardless of whether the subject wishes to continue participating.  
Withdrawal visit will consist in one day and the schedule of procedures will be the same as in Intermediate 
Visit 1. If the participant refuses to come to Center for Brain Health, the clinician will perform a clinical 
interview over the phone. 
6 Study Procedures/Evaluations 
6.1 Procedures/Evaluations 
Clinical evaluation:  all subjects will perform a standardized clinical evaluation (UDS 3.0) given to all 
participants seen at the NYU ADC. The purpose of this clinical evaluation is to establish that subjects are 
cognitively normal, identify concurrent medications that may act as confounders (e.g., benzodiazepines, 
trazodone, suvorexant), increase reproducibility of the clinical evaluation, and facilitate collaborative 
research with NACC (see Resource Sharing Plan). Depressive symptoms will be measured using the 
Geriatric Depression Scale (GDS)212;213. We will add information about: health insurance, annual household 
income, perceived discrimination (Index of Race-Related Stress [IRRS]-Brief Version B214), the Weinstein 
Noise Sensitivity Scale (WNSS)215, the Perceived Stress Scale (PSS)216 and the SF36 health behaviors 
survey217 to control for environmental, health and psychosocial factors that might disrupt sleep. In addition, 
all subjects will undergo complete fasting blood tests (CBC with differential and platelet count, highly 
sensitive CRP, ESR, total T3 and T4*, lipid profile, RPR*, comprehensive metabolic profile with insulin, 
folate*, homocysteine*, and vitamin B12*, SMA-18, HbA1c, hemogram)).  Subjects will then complete the 
WHICAP battery and the AMNART test4. The tests comprising this neuropsychological battery were chosen 
because unlike the UDS 3.0, they have race-specific norms5. We will construct three composite scores for 
general cognition, memory, and executive function from factor analyses. We will use total recall, delayed 
recall, and delayed recognition from the Buschke Selective Reminding Test218 to construct the memory 
composite. The executive functioning composite will be created using the Color Trail-Making Test (A and 
B)219, WAIS-R (Wechsler Adult Intelligence Scale-Revised), Similarities, Identities/Oddities subtest of the 
Mattis Dementia Rating Scale220, two cancellation tasks and semantic fluency for animals221. All of the above 
variables, together with phonemic fluency221, the 15-item Boston Naming Test222,  repetition task (high-
frequency phrases of the Boston Diagnostic Aphasia Examination[BDAE]223; and a comprehension task, 
will contribute to the composite for general cognition. Means and standard deviations (SD) will be 
calculated from baseline scores for non-demented WHICAP subjects controlling for age, race and years of 
education using robust norms. Z-scores for each of the cognitive measures will be averaged to create a 
composite z-score for each of the three domains. Only subjects diagnosed as cognitively normal with a z-
score >-1.25 SD of the mean in general cognition will be invited to participate. The time to complete the 
WHICAP test battery will range from 45-90 min. On visit 2, prior to the PET/MR scan, subjects will 
complete the UDS 3.0 cognitive evaluation to facilitate collaborative research with NACC.  
 
Ambulatory home monitoring for OSA followed by actigraphy: 
Subjects will be asked to monitor their sleep using sleep logs during one week. On the first night, OSA 
will be monitored using a WatchPAT (Itamar Medical, Tel Aviv, Israel) (Figure 8). We have experience 
using WatchPAT in AAs with very low failure rate (less than 1%). This self-applied device measures 
peripheral arterial volume changes using a finger-mounted plethysmograph. The information is collated 

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with pulse oximetry and is further analyzed using an automated algorithm. This algorithm associates 
arousals with measurement of O2Sat to determine respiratory effort-related arousals 
showing excellent sensitivity and specificity for identification of OSA, defined as 
AHI4%≥5 on full NPSG224. After automated analysis, all raw data and results are 
reviewed by Dr. Ayappa. Only subjects with an AHI4%<15 and AHI4%>5 with 
Epworth<10 will be invited to participate. Those cases with suspicion of OSA will be 
reviewed by Dr. Rapoport and Varga. If OSA is confirmed, they will be excluded and 
referred to a sleep specialist. Actigraphs (AMI, Ardsley, NY) (Figure 9) with off-wrist 
detection and a sleep diary will be provided to the subjects to use for the 7 days following 
the use of the WatchPAT. The purpose will be to record the sleep-wake cycle and provide 
estimates of total sleep time (TST) in the home. Actigraph will also provide bedtimes 
and wake times for NPSG N1-N2 in accordance with their usual sleep habits.  
 
Measurement of Slow Wave Sleep (SWS) characteristics using NPSG:  
Each in-lab NPSG will record sleep as recommended by the AASM225 as described in 
our previous work156. Electrode attachment will be performed between 8-9 PM. Subjects 
will be then asked to sit quietly and/or read until lights out at their habitual bedtime. 
NPSG N1 will be for habituation, N2 will be for data collection. Arousal index (AI), sleep 
staging, TST, sleep efficiency and wake after sleep onset (WASO) during NPSG will be 
scored by one trained technologist blinded to PET data using standard AASM criteria225. Participants will 
go home between N1-2 provided that they wear the actigraph with off-wrist detection, avoid naps or exercise 
and track their meals. SWS will be scored visually as: 1) TST in SWS in min. (SWS duration); and, 2) %TST 
spent in SWS (%SWS). SWS measurements will be measured in N2.  In addition, we will include: 1) slow 
wave activity (SWA): absolute SWA (defined as power between 0.5-4.0 Hz during NREM), relative SWA 
(SWA divided by power across all 0.4-50 Hz). NREM cycles will be defined as stages NREM2-3 of ≥15 min. 
terminated by REM or wakefulness of ≥5 min.  Delta power will be averaged relative to the number of 
epochs.  2)  SWS continuity: bouts of SWS will be defined as the duration of consecutive 30 sec. epochs of 
sleep scored as SWS, terminated by one or more epochs scored as another stage as described in our previous 
work226;227.   
 
Sleep-dependent Neuropsychological Tests: 
On NPSG N2, participants will be trained in our published 3-D virtual maze spatial navigational test (see 
Figure 10)141;156 Navigational memory represents a good model to study the effects of sleep-dependent 
memory consolidation. Rodent studies show that patterns of firing in hippocampal place cells during wake 
are replayed both in REM228 and NREM229 sleep. Behaviorally, sharp-wave ripple suppression impairs 
performance on a radial arm maze,230 while REM suppression impairs memory in the radial arm maze231 
and in the Morris water maze232. In humans, overnight sleep enhances virtual 
maze navigation performance233;234, while we have shown that maze 
completion time (CT) is attenuated after REM disruption176 and is correlated 
with SWA in elderly subjects188. Subjects will experience two different mazes 
at baseline and at the 2.5-year follow-up, and mazes will be counterbalanced 
across subjects for which maze is experienced first. Both mazes have been 
designed such that optimal CT is equivalent assuming perfect knowledge of the 
maze layout.  Maze performance will be expressed as % change across sleep in 
maze CT compared to baseline CT before sleep. We have chosen a maze over a 
word-pair test105;235;236 because: 1) it taxes the hippocampus (more than a 
word-pair tasks would); 2) it’s ecologically relevant to AD (i.e. spatial 
disorientation is one of the early clinical AD-symptoms); and 3) there are equivalent rodent models that 
lend insight into the underlying electrophysiological mechanisms (i.e. sharp-wave ripples, which cannot be 
captured with surface EEG).  
 
PiB PET and MRI scans: 
On visit 4, baseline and follow-up subjects will receive a single dose of 11.12 mCi PiB and perform a 
dynamic 60 min amyloid PiB PET-MR scan 35 min after injection.. The radioactive drug (PiB) shall meet 
appropriate chemical, pharmaceutical, and radionuclidic standards. The dose will be radioassayed proper 
to administration to ensure dosimetry data is correct. Further, the mass of the PiB is not expected to 
produce a pharmacologic response. PET/MR scans will be performed on an integrated 3T PET/MR 
Figure 9. Actigraph 
Figure 
8.
WatchPAT 
Figure 10. Bird’s eye view of 
virtual maze 

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(Siemens Biograph mMR, software Syngo MR B18P). For anatomic coregistration, a sagittal 3-D MPRAGE 
sequence will be performed (208 slices, 1mm isotropic voxels). Attenuation correction will be performed 
using a Dixon μ-map with a superimposed bone compartment and linear AC developed at NYU237. 
Modifying the linear AC value and superimposing a model-based bone compartment reduces the whole-
brain SUV estimation bias of Dixon-based PET/MR AC by 95% compared with reference PET/CT AC 
(p<.05), resulting in a residual −0.3% SUV mean bias237. Ultrashort echo time (UTE) will also be acquired 
and combined to the Dixon μ-map to incorporate the bone tissue238.  Simultaneous PET-MR acquisition 
eliminates the need of registering the PiB images to MNI. Instead, we will use the MPRAGE for registration, 
which offers a fine volumetric resolution and high contrast ratio required to precisely differentiate between 
GM and WM. For each patient, the MPRAGE image will be automatically segmented into, neocortical and 
cerebellar hemisphere GM regions of interest (ROIs) using FreeSurfer. These GM neocortical ROIs will be 
collapsed to yield four large volume-weighted ROIs that span prefrontal, lateral temporal, parietal cortex 
and anterior/posterior cingulate gyrus cortices (as described in239). An ADPiBmask index will be the primary 
variable of interest in this study, derived by averaging these mean SUV values to a reference region 
containing the supratentorial WM and whole cerebellum. PiB+ will be defined as a ADPiBmask ≥1.4.  The 
combined region will be used to calculate longitudinal estimates of change in PiB uptake.  
Images for exclusion and structural brain measurements of middle prefrontal cortex (mPFC). Along with 
the PET acquisition we will acquire several sets of images intended to screen for brain disease, stroke or 
extensive white matter lesions. We will we use a thin slice 3D sagittal T1 MPRAGE sequence. Parameters 
are: TR 2100 ms; TE 4.37 ms; TI 900 ms; flip angle 8°; matrix 240 (read) x 256 (phase) x 208 (partitions); 
FOV 256 (read) x 192 (phase) x 240 (partitions) mm; iPAT 2; voxel size 1.0x1.0x1.0 mm; NEX 1; acquisition 
time 4.35’. Whole brain and cortical volumes: automatic brain segmentation, cortical surface reconstruction 
and parcellation will be performed using FreeSurfer (surfer.nmr.mgh.harvard.edu). Segmentations will 
undergo qualitative reviews and volumes will be residualized to intracranial volume (ICV)169.  
Fluid-attenuated inversion recovery (FLAIR): We will obtain complete brain coverage using 3D sagittal 
FLAIR SPACE sequences to quantify white matter lesions (WML). Parameters are: TR 6000 ms; TE 325 
ms; TI 2100 ms; matrix 256 (read) x 248 (phase) x 176 (partitions); FOV 256 (read) x 248 (phase) x 176 
(partitions) mm; iPAT 2; voxel size 1.0x1.0x1.0 mm; NEX 1; acquisition time 2.56’. WML volume (mL) is 
considered a surrogate marker of small vessel disease.240 It will be obtained using an semi-automatic 
approach based on hyperintense (≥mean+2.5SD) voxels in WM with our locally developed software 
FireVoxel241;242 (files.nyu.edu/hr18/public). WML volume will be subdivided into periventricular (PWML) 
and deep (DWML). 
Diffusion Kurtosis Imaging (DKI) is an extension of diffusion tensor imaging (DTI)243 that provides the 
information obtained from DTI, plus additional non-Gaussian diffusion parameters,244 as well as new WM 
tract integrity (WMTI) metrics245;246 that are specific to underlying pathology: (a) axonal water fraction 
(marker of axonal density); (b) Daxon, diffusivity inside the axons (marker of axonal injury); and (c) De|| 
and De┴, extra-axonal axial and radial diffusivity (markers of extracellular inflammation, gliosis and 
demyelination). We will use an optimized protocol in terms of number of shells (b-values) and encoding 
directions, providing the best coverage of q-space for diffusion and kurtosis tensors estimation within a 
short acquisition time (~7 min). The protocol can be summarized as follows: TR 8200 ms; TE 96 ms; b=0 
(4 averages), b=250 (6 directions), b=1000 (20 directions), b=2000 (30 directions), s/mm2, b=0 with 
reversed phase encoding direction (1 average); 50 axial slices; FOV 230 (read) x 230 (phase) mm2; voxel 
size 2.5x2.5x2.5 mm3.  The DKI data will be used to derive parametric maps of DTI and DKI, followed by 
derivation of WMTI maps using our in-house developed processing pipeline (github.com/NYU-Diffusion 
MRI/Diffusion-Kurtosis-Imaging).  Next, all maps will be transformed into standard space using FMRIB’s 
Software Library.  Mean values will then be extracted for each metric to assess the microstructural WM 
damage beyond lesions visible on FLAIR.  
  
Individual Genetic Ancestry Estimation 
Allele frequencies will be ascertained from Utah residents with Northern and Western European 
ancestry and West African (Yoruban from Nigeria) samples available in the HapMap database. Individual 
% African ancestry (%AF) estimates from 0-100 will be computed using a maximum likelihood method for 
inferring individual admixture247. Briefly, an algorithm is used to compute the probability of observing a 
marker genotype given ancestral allele frequencies at a locus. Summing over the logs of individual locus 
probabilities combines information across multiple loci. The admixture proportion that maximizes the 

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probability of obtaining the observed genotype is the maximum likelihood estimate of ancestry for the 
individual199;248. 
6.2 Laboratory Procedures/Evaluations 
 
SOURCES OF MATERIALS: 
The raw data collected in the current proposal will include MRI and PET scans, blood samples for DNA 
genotyping, neuropsychological test scores, and clinical data from medical, neurological, psychiatric exams, 
sleep, cardiologic and respiratory evaluations. Only approved study personnel  will interact with 
participants and have access to subject information. Data will be collected during full-day in-home and 
nocturnal in-laboratory (polysomnography) sleep studies that are standard clinical practice.  Medical 
records will be kept in accordance with state and federal laws concerning the privacy and confidentiality of 
medical information. All efforts will be taken to maintain subject confidentiality and research will be 
conducted following good clinical practices. Each subject will be assigned a unique code number.  
Confidentiality will be maintained by keeping paper study data in a locked drawer in a locked office. All 
electronic data will be stored on the Mount Sinai Integrative Sleep Center (MSISC) and NYU Center for 
Brain Health (CBH) databases such as RedCap, which are password protected and stored within the secure 
Mount Sinai Medical Center Information Technology (MSMCIT) and NYU Langone Medical Center IT 
(NYULMCIT) systems.  Data will only be available to the key personnel.  All have taken HIPAA and IRB 
tutorials. 
 
6.3 Study Specific Biospecimens 
6.3.1 Specimen Collection Procedures 
Collection of Blood. We will collect blood at Visit 1 for the baseline and follow-up visits to perform 
clinical labs and 10 ml of fresh blood to extract DNA (only at the baseline visit) the total amount of blood 
for both baseline and follow-up visits will be approximately 80cc’s. The  fresh blood samples will be sent 
to LGC Genomics where DNA will be extracted and sent back to NYU after GWAS analyses. All data 
regarding DNA samples will be entered into the ADC-CBH database for sample tracking. While a sample 
is being processed, one back-up sample with fresh blood will be maintained. 
6.3.2 Specimen Preparation, Handling, and Storage 
6.3.2.1 Supplies: 
 
 
 
2 PaxGene blood DNA tubes (catalog number 761115) 
 
3 purple-topped tubes,1 red-topped tube, and 2 gold-topped tubes 
 
27 Nalgene™ General Long-Term Storage Cryogenic Tubes (Fisher catalog number 5000-0020). 
6.3.2.2 General blood handling considerations: 
The release of cellular material due to hemolysis into the serum or plasma may introduce additional 
confounding factors in downstream analysis of such samples. When hemolysis is observed (pink to red tinge 
in sample that persists after one cycle of centrifuging), this information will be recorded in the 
plasma/serum (PS) log 
 
6.3.2.3 Serum handling considerations (red topped tubes) 
Serum samples should be left at room temperature at least 30 minutes. If the subject is taking any kind 
of anticoagulant or blood thinner (warfarin, factor Xa inhibitors, heparin, thrombin inhibitors, antiplatelet 
drugs) (variable name ‘anticoag_meds’) at the time of sample collection, leave at least 45 minutes. Check 

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if the clot has formed at 45 and 60 minutes. Record this information in the plasma/serum log (variable ‘clot 
time in minutes’). Steps: 
o 
Check medication list provided by the subject. 
o 
Record any kind of anticoagulant or blood thinner in the PS log 
o 
Record time of blood draw in the PS log. 
o 
Allow blood to clot for a minimum of 30, 40, or 60 minutes in a vertical position at room 
temperature. 
o 
Observe a dense clot. 
o 
Record time of centrifuge start in the PS log. 
6.3.2.4 Plasma Handling Considerations (lavender topped EDTA tubes) 
The volume of blood collected in each tube and adequate mixing of the sample into the additive are 
critical steps. 
o 
Record time of blood draw in the PS log. 
o 
Fill tubes. 
o 
Gently invert tubes 8-10 times. 
o 
Centrifuge at the same time as the serum. 
6.3.2.5 Temperature and Light: 
Protect samples from extreme temperatures. Transport with icepacks on the sides. Make sure icepacks 
are never in direct contact with the samples. Do not place blood tubes in windows as direct sunlight can 
cause the red cells to lyse, and may impact the usability of the specimen. 
6.3.2.6 Processing: 
o 
Put 1cc of whole blood from purple tube in two small vial for genetics (vials GEN1-2) 
o 
 Heat centrifuge to 21 degrees. 
o 
 Spin bloods on at 3000 RPM during 15 minutes. 
o 
 Aliquot EDTA plasma into vials PLM1-10. (1.5cc per vial.) 
o 
 Aliquot EDTA WBC (buffy coat) into vials WBC1-2. (0.5 cc per vial.) 
o 
 Aliquot serum into vials SER1-4. (1.5 cc per vial.) 
o 
Put samples into cryogenic box. 
o 
Transport box to -80C with icepacks on the side. 
6.3.3 Specimen Shipment 
Specimen Shipment: 
Specimens will be shipped on dry ice for DNA extraction and ApoE4 genotyping to LGC Genomics for 
DNA extraction (LGC, 100 Cummings Center, Suite 420H, Beverly, MA 01915, US) and NCRAD once a year. 
Samples will include the 4 digit subject ID only. 
6.4 Questionnaire Administration. 
All questionnaires are part of the clinical evaluation and are included as addendums 
7 Safety and Adverse Events 
7.1 Definitions 
7.1.1 Unanticipated Problems Involving Risk to Subjects or Others: 
Any incident, experience, or outcome that meets all of the following criteria:  
 Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as 
the IRB-approved protocol or consent form, the investigators brochure, etc.). 

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 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
 Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
 Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
 Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
 results in study withdrawal 
 is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 a congenital anomaly or birth defect 
 an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance.   They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization, or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during 
the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the 
end of the study, any new clinically significant findings/abnormalities that meet the definition of an 
adverse event must also be recorded and documented as an adverse event.  
 

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Post-study Adverse Event 
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  The 
investigator should notify the study sponsor of any death or adverse event occurring at any time after a 
subject has discontinued or terminated study participation that may reasonably be related to this study.  
The sponsor should also be notified if the investigator should become aware of the development of cancer 
or of a congenital anomaly in a subsequently conceived offspring of a subject that has participated in this 
study.  
7.2 Recording of Adverse Events 
At each contact with the subject, the investigator must seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events should be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case report 
form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results should 
recorded in the source document, though should be grouped under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of each event 
should be followed until resolution, stabilization, or until it has been determined that the study treatment 
or participation is not the cause.  Serious adverse events that are still ongoing at the end of the study 
period must be followed up to determine the final outcome.  Any serious adverse event that occurs after 
the study period and is considered to be possibly related to study participation should be recorded and 
reported immediately. 
7.3 Reporting of Serious Adverse Events and Unanticipated Problems 
 
For Narrative Reports of Safety Events 
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of 
the initial report includes: 
 
Study identifier 
 
Study Center 
 
Subject number 
 
A description of the event 
 
Date of onset 
 
Current status 
 
Whether study treatment was discontinued 
 
The reason why the event is classified as serious 
 
Investigator assessment of the association 
between the event and study treatment 
7.3.1 Investigator reporting: notifying the IRB 
Federal regulations require timely reporting by investigators to their local IRB of unanticipated problems 
posing risks to subjects or others.  The following describes the NYULMC IRB reporting requirements, 
though Investigators at participating sites are responsible for meeting the specific requirements of their 
IRB of record.  
 
Report Promptly, but no later than 5 working days: 
Researchers are required to submit reports of the following problems promptly but no later than 5 
working days from the time the investigator becomes aware of the event: 
 
Unanticipated problems including adverse events that are unexpected and related 
– Unexpected: An event is “unexpected” when its specificity and severity are not accurately 
reflected in the protocol-related documents, such as the IRB-approved research protocol, any 
applicable investigator brochure, and the current IRB-approved informed consent document 
and other relevant sources of information, such as product labeling and package inserts.  

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– Related to the research procedures: An event is related to the research procedures if in the 
opinion of the principal investigator or sponsor, the event was more likely than not to be 
caused by the research procedures.  
– Harmful: either caused harm to subjects or others, or placed them at increased risk 
 
Other Reportable events: 
The following events also require prompt reporting to the IRB, though no later than 5 working days: 
 Complaint of a research subject when the complaint indicates unexpected risks or the 
complaint cannot be resolved by the research team. 
 Protocol deviations or violations (includes intentional and accidental/unintentional 
deviations from the IRB approved protocol) for any of the following situations:  
– one or more participants were placed at increased risk of harm  
– the event has the potential to occur again 
– the deviation was necessary to protect a subject from immediate harm 
 Breach of confidentiality 
 Incarceration of a participant when the research was not previously approved under Subpart 
C and the investigator believes it is in the best interest of the subject to remain on the study. 
 New Information indicating a change to the risks or potential benefits of the research, 
in terms of severity or frequency. (e.g. analysis indicates lower-than-expected response rate or a 
more severe or frequent side effect; Other research finds arm of study has no therapeutic value; 
FDA labeling change or withdrawal from market) 
 
Reporting Process 
The reportable events noted above will be reported to the IRB using a Reportable New Information 
submission and will include a description of the event with information regarding its fulfillment of the 
above criteria, follow-up/resolution, and need for revision to consent form and/or other study 
documentation. Copies of each report and documentation of IRB notification and receipt will be kept in 
the Clinical Investigator’s study file. 
 
 
8 Study Oversight 
 
It is the responsibility of the Principal Investigator (Dr. Osorio) to oversee the safety of the study 
alongside with the Co-Investigator (Dr. Jean-Louis).  This safety monitoring will include careful assessment 
and appropriate reporting of AEs as noted above, as well as the construction and implementation of a site 
data and safety-monitoring plan. Medical monitoring will include a regular assessment of the number and 
type of serious adverse events. 
 
The PIs will work to develop all aspects of the proposed study including direct oversight, staff supervision, 
engagement of the Community Advisory Board (CAB), supervision of staff, enrollment and monitoring of 
eligible participants, acquisition and management of subjective and clinical data, analysis and 
dissemination of study results. They will also ensure that stated aims are achieved in a timely manner.  
Moreover, each PI will focus on different but related aspect of the specific aims based on their primary 
expertise.   
 
 

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9 Statistical Considerations 
9.1 Study Hypotheses 
1. 
Hypothesis 1.1: poor SWS characteristics (short SWS duration, low %SWS, low relative SWA, low SWS 
continuity and high AI) at baseline will be associated with high %AF. Hypothesis 1.2: psychosocial 
factors (e.g. perceived discrimination) will partially moderate the above relationships. 
2. 
Hypothesis 2.1:  race will be associated with longitudinal increases in the annual rate of ADPiBmask 
change. Hypothesis 2.2: the effect of race in terms of longitudinal increases in ADPiBmask will be 
partially explained by poor relative SWA at baseline.  
3. 
Hypothesis 3.1: race will be associated with longitudinal changes in global cognition, memory, executive 
function and sleep-dependent spatial navigational memory. Hypothesis 3.2: the association of race in 
terms of cognitive decline will be partially explained by poor relative SWA at baseline. Exploratory 
Hypothesis: absence of improvement in sleep dependent memory consolidation at baseline will be 
associated with longitudinal decreases in global cognition, memory and executive function. 
 
9.2 Sample Size Determination 
Power was assessed under the assumption that dropout replacement will allow complete data to be 
acquired from 200 subjects. Based on the existing literature23-32, the coefficient of variation (CV) of SWS 
duration is anticipated to be as high as 90% among AA and 40% among whites. Baseline data from 150 AA 
and 60 whites will therefore provide 80% power at the 5% significance level to detect a mean SWS duration 
among whites that is at least 28% higher than among AA. Based on PD4, the CV of PiB uptake at baseline 
is anticipated to be as high as 35% among AA and 25% among whites, providing 80(90)% power at the 5% 
significance level to detect a mean PiB uptake among AAs that is at least 13%(15%) higher than in whites. 
For Aim 1, the study will have 80% power at the 5% significance level to detect correlations of magnitude 
|r|=0.20   (the study from Halder et al39 showed an R2 of 11, implying an even greater correlation of 0.33 
can be expected in our study). The multivariable regression analysis will have 80% power to detect SWS 
characteristics that can explain 3% of the variance in the longitudinal change in ADPiBmask (Aim 2) or 
cognition (Aim 3) after adjusting for covariates that together explain at least 25% of the variance in 
ADPiBmask/cognition. The detectable effect of 3% variance explained, implies the study can detect partial 
correlations of magnitude 0.1 between SWS and the outcomes adjusted for the cofactors. It is noted that the 
power of the multivariable analyses will improve if the covariates explain >25% of the variance. The study 
will have 80% power to detect sleep measures that explain 10% of the variance in the ADPiBmask ratio even 
if the covariates explain a negligible percentage of the variance.  
 
9.3 Statistical Methods 
 
General considerations: we will incorporate standard techniques such as omnibus tests and appropriate 
adjustments to significance (α) levels (e.g., Bonferroni correction) for post-hoc contrasts to control for 
multiple comparisons. Both selection and attrition biases might occur. Appropriate techniques (e.g., 
Heckman 2-stage approach (GEE Probit Model)254;255 and Monte Carlo (EM algorithm)256 will be used to 
address biases or missing data. Attributes of those who withdrew to follow-up will be contrasted with 
completers to determine sources of attrition biases. Since only two time points will be analyzed, we will use 
linear regression models with the annual rate of amyloid change as dependent variable. Significance will be 
defined by p<.05 where p will be Bonferroni corrected when testing post-hoc contrasts.  
 Hypothesis (1): H1.1) for %AF associations, linear regression models, with each of SWS characteristics 
as the dependent variable, will be regressed on %AF controlling for age, sex, BMI, AHI, TST, sleep 
efficiency and WASO. H1.2) This model will test interaction by including the best SWS predictor as 
dependent variable, the psychosocial factor as a classification factor, %AF and the term created as the 
cross product of psychosocial factors and %AF.  
 Hypothesis 2-3 (H2-3): First we will calculate the associations between race and ADPiBmask 
represented both as binary (AA vs. white) and numeric (%AF). Further analyses will use the 
representation (s) of race significantly associated with amyloid burden. Second, we will use hierarchical 

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linear regression, with rate of change of ADPiBmask as the dependent variable and race as independent, 
adjusting for the matching factors: age, sex, BMI, education and annual income (block 1); ApoE4 and 
ABCA7 (block 2); DWML volumes, DKI indices and mPFC volume (block 3); and SWS characteristic (e.g. 
relative SWA) (block 4). Other covariates (e.g., psychosocial) will be included in the final models if 
significantly different between AAs and whites as indicated by unequal variance t tests. Although we 
anticipate that relative SWA will be the best predictor of longitudinal change in ADPiBmask, the best fitting 
model will be then replicated with each of the other SWS characteristics not listed before.  On a final step, 
we will test whether the effect of SWS on amyloid deposition is different (i.e., stronger) among AAs. The 
model would include ADPiBmask change, the binary indicator of race (AA=1 vs. white=0) and SWA as 
described in H1.2. If the interaction is significant, it will imply that the effect of SWA on amyloid varies as 
a function of race. The sign of the estimated coefficient for this term would indicate whether SWA has a 
significantly stronger or weaker effect among AA. Exploratory Hypothesis: cognitive z-score change in 
subjects that show improvement in maze CT will be compared with those that don’t show improvement 
using ANCOVA controlling for age, sex, BMI, race, education and ApoE4 status. 
 Post-hoc analyses: a subset of post-hoc analyses will be performed by controlling by PiB levels at 
baseline and by splitting the sample into PiB+ and PiB- at baseline and performing a separate analysis for 
each subset. Stratified analyses will also be performed for men and women, as well as for AAs and whites. 
In addition, we will formally test the impact of PiB status (defined as PiB SUVR≥1.4) on the association of 
sleep measures with longitudinal increases in ADPiBmask. Although we do not anticipate that sleep or SWS 
characteristics will change over the follow-up period, post-hoc analyses will be performed by assessing 
longitudinal changes in the sleep measures as correlates and predictors of longitudinal changes in the 
outcomes measures, using paired sample t-tests to assess the change in outcomes and sleep.  
10 Source Documents and Access to Source Data/Documents 
 
Source data is all information, original records of clinical findings, observations, or other activities in a 
study necessary for the reconstruction and evaluation of the study.  Source data are contained in source 
documents.  Examples of these original documents, and data records include: hospital records, clinical and 
office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, copies or transcriptions certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, 
subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments 
involved in the study.  
 
The study case report form (CRF) is the primary data collection instrument for the study.  All data 
requested on the CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left 
blank because the procedure was not done or the question was not asked, write “N/D”.  If the item is not 
applicable to the individual case, write “N/A”.  All entries should be printed legibly in black ink.  If any entry 
error has been made, to correct such an error, draw a single straight line through the incorrect entry and 
enter the correct data above it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE 
OUT ERRORS.  For clarification of illegible or uncertain entries, print the clarification above the item, then 
initial and date it. 
 
Access to study records will be limited to IRB-approved members of the study team. The investigator 
will permit study-related monitoring, audits, and inspections by the IRB/EC, the sponsor, government 
regulatory bodies, and University compliance and quality assurance groups of all study related documents 
(e.g. source documents, regulatory documents, data collection instruments, study data etc.).  The 
investigator will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable University compliance and quality assurance offices. 
 

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11 Ethics/Protection of Human Subjects 
11.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with Regulations for the 
Protection of Human Subjects of Research codified in 45 CFR Part 46. 
11.2 Institutional Review Board 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval before being used. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the protocol will 
require review and approval by the IRB before the changes are implemented to the study. All changes to the 
consent form will be IRB approved; a determination will be made regarding whether previously consented 
participants need to be re-consented. 
11.3 Informed Consent Process 
Informed consent is obtained from each subject using IRB approved consent forms. In the consent form 
and in discussion with an investigator, participants will be advised fully of the procedures to be used, the 
amount of time required of them, the possible risks and benefits of the procedures, their right to refuse 
participation in the study without prejudice, their right to terminate participation at any moment without 
prejudice, and the name and telephone number of the Principal Investigator (Dr. Osorio). In the informed 
consent form (ICF), participants will be told that the information they provide and all findings will be kept 
strictly confidential, with access limited to the research staff and the possible exception of state or federal 
regulatory personnel. Several steps will be taken to minimize reactions of discomfort, embarrassment, 
fatigue, or boredom. 
11.3.1 Consent/Assent and Other Informational Documents Provided to 
Participants 
Consent forms describing in detail the study procedures, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting procedures. The 
following consent materials are submitted with this protocol: 
– Documentation of Consent Process 
– Informed Consent Form 
– Screening Form 
11.3.2 Consent Procedures and Documentation 
Potential study participants will be pre-screened at recruitment sites in a quiet and private area by the 
study coordinators. A waiver of documentation of consent will be uploaded to the IRB so that people can 
give verbal consent at the time of the pre-screen. A document with eligibility questions will also be uploaded 
for approval as a screening form. Given the strict exclusion criteria for this study, a waiver of documentation 
of consent is necessary in order to avoid wasting participant’s time if something makes them clearly 
ineligible.   The pre-screening interview is minimal risk as it involves only the minimum necessary 
information collected to determine eligibility. This will involve the CES-D, MOSS-F, ARES-TM 
questionnaire’s and review of medical history and medications history.  For eligible subjects who 
subsequently sign consent/authorization to participate, the information becomes part of the subject’s de-
identified study record.  However, information collected during pre-screening will be destroyed 
immediately if a person is deemed ineligible or decides not to participate in the study. 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Extensive discussion of risks and 
possible benefits of participation will be provided to the participants and their families. Consent forms will 
be IRB-approved and the participant will be asked to read and review the document. The investigator will 
explain the research study to the participant and answer any questions that may arise. All participants will 

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receive a verbal explanation in terms suited to their comprehension of the purposes, procedures, and 
potential risks of the study and of their rights as research participants. Participants will have the 
opportunity to carefully review the written consent form and ask questions prior to signing. The participants 
should have the opportunity to discuss the study with family members or think about it prior to agreeing to 
participate. The participant will sign the informed consent document prior to any procedures being done 
specifically for the study. The participants may withdraw consent at any time throughout the course of the 
study. A copy of the signed informed consent document will be given to the participants for their records. 
The rights and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
 
A copy of the signed informed consent document will be stored in the subject’s research record. The 
consent process, including the name of the individual obtaining consent, will be thoroughly documented in 
the subject’s research record. Any alteration to the standard consent process (e.g. use of an interpreter, 
consent document presented orally, etc.) and the justification for such alteration will likewise be 
documented.  
 
11.4 Participant and Data Confidentiality 
Information about study subjects will be kept confidential and managed according to the requirements 
of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a 
signed subject authorization informing the subject of the following:  
 
What protected health information (PHI) will be collected from subjects in this study 
 
Who will have access to that information and why 
 
Who will use or disclose that information  
 
The rights of a research subject to revoke their authorization for use of their PHI.  
 
In the event that a subject revokes authorization to collect or use PHI, the investigator, by regulation, 
retains the ability to use all information collected prior to the revocation of subject authorization.  For 
subjects that have revoked authorization to collect or use PHI, attempts should be made to obtain 
permission to collect at least vital status (i.e. that the subject is alive) at the end of their scheduled study 
period. 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and the 
sponsor(s) and their agents. This confidentiality is extended to cover testing of biological samples and 
genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No information 
concerning the study or the data will be released to any unauthorized third party without prior written 
approval of the sponsor. 
 
The study monitor, other authorized representatives of the sponsor, or representatives of the IRB may 
inspect all documents and records required to be maintained by the investigator, including but not limited 
to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The 
clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long 
a period as dictated by local IRB and Institutional regulations. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at  The Center for Brain Health. This will not include the participant’s contact 
or identifying information. Rather, individual participants and their research data will be identified by a 
unique study identification number. The study data entry and study management systems used by clinical 
sites and Center for Brain Health research staff will be secured and password protected. At the end of the 
study, all study databases will be de-identified and archived at the Center for Brain Health. 
 

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To further protect the privacy of study participants, a Certificate of Confidentiality will be obtained from 
the NIH. This certificate protects identifiable research information from forced disclosure. It allows the 
investigator and others who have access to research records to refuse to disclose identifying information on 
research participation in any civil, criminal, administrative, legislative, or other proceeding, whether at the 
federal, state, or local level. By protecting researchers and institutions from being compelled to disclose 
information that would identify research participants, Certificates of Confidentiality help achieve the 
research objectives and promote participation in studies by helping assure confidentiality and privacy to 
participants. 
 
This study is a genome-wide association study and will comply with the NIH Policy for Sharing of Data 
Obtained in NIH Supported or Conducted GWAS, which calls for investigators funded by the NIH for GWAS 
to 1) share de-identified genetic (genotypic and phenotypic) data through a centralized NIH data repository; 
and 2) submit documentation that describes how the institutions have considered the interests of the 
research participants, such as privacy and confidentiality. Submission of data to the NIH GWAS repository 
will be consistent with the permissions and limitations delineated on the study consent signed by study 
participants. 
11.4.1 Research Use of Stored Human Samples, Specimens, or Data 
 Intended Use: Samples and data collected under this protocol may be used to study the APOE 
gene. Samples are stored indefinitely.  No diagnostic genetic testing will be performed. 
 Storage: Access to stored samples over the course of the study will be limited to the PI and co-
investigators. Samples and data will be stored using codes assigned by the investigators. Data will 
be kept in password-protected computers. Only investigators will have access to the samples and 
data as well as the linking key to re-identify samples. 
 Tracking: Data will be tracked using an Excel tracking file. 
o 
Disposition at the completion of the study: All stored samples will be sent to the Center 
for Brain Health (CBH) biorepository. Study participants who request destruction of 
samples will be notified of compliance with such request and all supporting details will be 
maintained for tracking. 
 
Future Use of Stored Specimens: 
 
Subjects will have the option to allow their leftover blood and DNA samples to be banked indefinitely 
for future research related to studies on early diagnosis of Alzheimer’s, disease and/or mechanism of 
neurodegeneration. After the study is completed, the de-identified, archived data will be transmitted to and 
stored at the CBH Biorepository, under the supervision of Dr. Osorio, for use by other researchers including 
those outside of the study. Permission to transmit data to the CBH Biorepository will be included in the 
ICF. The CBH Biorepository will also be provided with a code-link that will allow linking the biological 
specimens with the phenotypic data from each participant, maintaining the masking of the identity of the 
participant which the PI will have access to as well as study team members he gives permission to on a case 
by case basis.   During the conduct of the study, an individual participant can choose to withdraw consent 
to have biological specimens stored for future research. However, withdrawal of consent with regard to 
biosample storage will not be possible after the study is completed. When the study is completed, access to 
study data and/or samples will be provided through the CBH Biorepository. Samples are stored with the 
study number, subject ID number, and book period number so they can be withdrawn if necessary.  
12 Data Handling and Record Keeping 
 
Data and Safety Monitoring 
 A data and safety monitoring plan has been established to ensure the safety of all participants involved in 
the study and to ensure the validity and integrity of the data. Dr. Andrew Varga will conduct data verification 
and validation of all parameters collected for the study against the source documentation in accordance 
with the following plan. Periodic discussion every six months between the P.I., Dr. Jean-Louis, and Dr. 
Varga will ensure a consistent approach to data collection and monitoring techniques for all subjects 
regarding all relevant information and study procedures such as participant reports, data acquisition 

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methods, and any safety/adverse events. The primary responsibility of the DSM will be to monitor the 
progress of the study and recommend modifying the trial or terminating the trial as appropriate.  
 
All studies will be clinically read by a sleep physician  from the Icahn School of Medicine at Mount Sinai. 
These reports will be shared with study subjects. Collected raw data, and processed data exports from the 
sleep studies will stay in a shared drive based at NYU.  Data will be double entered into RedCap by the study 
coordinators and study interns 
 
12.1 Data Collection and Management Responsibilities 
Data collection is the responsibility of the study staff at the site under the supervision of the site PI. The 
investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the data 
reported. 
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity of reproduced copies. When making changes or corrections, 
cross out the original entry with a single line, and initial and date the change. DO NOT ERASE, 
OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the electronic CRF (eCRF) will be provided for use as source documents and maintained for 
recording data for each participant enrolled in the study. Data reported in the eCRF derived from source 
documents should be consistent with the source documents or the discrepancies should be explained and 
captured in a progress note and maintained in the participant’s official electronic study record. 
 
Clinical data and clinical laboratory data will be entered into RedCap, a data capture system provided by 
the NYU School of Medicine . The data system includes password protection and internal quality checks, 
such as automatic range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical 
data will be entered directly from the source documents. Subject information/data are downloaded into 
NYU based drives. Mount Sinai teams will log into our drives via the NYU portal with a username and 
password to process the sleep data and upload the study reports  
 
 
 
12.2 Study Records Retention 
Study documents will be retained for the longer of 3 years after close out or 5 years after final 
reporting/publication. These documents should be retained for a longer period, however, if required by 
local regulations. No records will be destroyed without the written consent of the sponsor, if applicable. It 
is the responsibility of the sponsor to inform the investigator when these documents no longer need to be 
retained. 
12.3 Protocol Deviations 
A protocol deviation is any noncompliance with the study protocol. The noncompliance may be either 
on the part of the participant, the investigator, or the study site staff. As a result of deviations, corrective 
actions are to be developed by the site and implemented promptly. It is the responsibility of the site to use 
continuous vigilance to identify and report deviations within 5 working days of identification of the protocol 
deviation, or within 5 working days of the scheduled protocol-required activity. All deviations must be 
addressed in study source documents, reported to the NIA Program Official. Protocol deviations must be 
reported to the local IRB per their guidelines. The site PI/study staff is responsible for knowing and 
adhering to their IRB requirements. 
12.4 Publication and Data Sharing Policy 
Our plan to share materials and our management of intellectual property will be in accordance with our 
institution’s and NIH policies and guidelines. All investigators involved in this project will adhere to NIH’s 
Data Sharing Policy and Implementation Guidance of March 5, 2003 and NIH Grants Policy on Sharing of 

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Unique Research Resources including the “Sharing of Biomedical Research Resources: Principles and 
Guidelines for Recipients of NIH Grants and Contracts” issued in December, 1999. All reasonable requests 
for additional information or tools developed in-house that are not available from commercial sources will 
be met in a timely fashion. Our image-analysis software FireVoxel can be downloaded at 
http://wp.nyu.edu/firevoxel/ 
13 Study Finances 
13.1 Funding Source 
This grant will be funded by the NIA/NIH 
13.2 Costs to the Participant 
All study-related costs will be paid by the National Institute of Health (NIH). Participants will not incur 
any costs as a result of participating in this study. 
13.3 Participant Reimbursements or Payments 
 
Participants will receive $150 per NPSG and $200 for the PET-MR scan for a total of $500 for the baseline 
evaluation and $500 for the 24 fu visit. Subjecs will be compensated with $75 for the 12 month fu visit, 
totaling $1,075 for entire study completion. Payments are incremental and not contingent upon completing 
the study.  
 
14 Study Administration 
14.1 Study Leadership 
Not applicable.  
15 Conflict of Interest Policy 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this study will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a way 
that is appropriate to their participation in the study. The study leadership in conjunction with the NIH/NIA 
has established policies and procedures for all study group members to disclose all conflicts of interest and 
will establish a mechanism for the management of all reported dualities of interest.  
 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial 
gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by the 
NYU Langone Conflict of Interest Committee with a Committee-sanctioned conflict management plan that 
has been reviewed and approved by the study sponsor prior to participation in this study.  All NYULMC 
investigators will follow the applicable conflict of interest policies. 
 
 

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16 References 
BIBLIOGRAPHY AND REFERENCES CITED: 
 
(1) Gooneratne NS, Richards KC, Joffe M et al. Sleep disordered breathing with excessive daytime sleepiness 
is a risk factor for mortality in older adults. Sleep 2011;34:435-442. 
 
(2) Stone KL, Blackwell TL, Ancoli-Israel S et al. Sleep Disordered Breathing and Risk of Stroke in Older 
Community-Dwelling Men. Sleep 2016;39:531-540. 
 
(3) Munoz R, Duran-Cantolla J, Martinez-Vila E et al. Severe sleep apnea and risk of ischemic stroke in the 
elderly. Stroke 2006;37:2317-2321. 
 
(4) Grober E, Sliwinski M. Development and validation of a model for estimating premorbid verbal intelligence 
in the elderly. J Clin Exp Neuropsychol 1991;13:933-949. 
 
(5) Stern Y, Andrews H, Pittman J et al. Diagnosis of dementia in a heterogeneous population. Development 
of a neuropsychological paradigm-based diagnosis of dementia and quantified correction for the effects of 
education. Arch Neurol 1992;49:453-460. 
 
(6) Chen HY, Panegyres PK. The Role of Ethnicity in Alzheimer's Disease: Findings From The C-PATH Online 
Data Repository. J Alzheimers Dis 2016;51:515-523. 
 
(7) Gurland BJ, Wilder DE, Lantigua R et al. Rates of dementia in three ethnoracial groups. Int J Geriatr 
Psychiatry 1999;14:481-493. 
 
(8) Dilworth-Anderson P, Hendrie HC, Manly JJ, Khachaturian AS, Fazio S. Diagnosis and assessment of 
Alzheimer's disease in diverse populations. Alzheimers Dement 2008;4:305-309. 
 
(9) Potter GG, Plassman BL, Burke JR et al. Cognitive performance and informant reports in the diagnosis of 
cognitive impairment and dementia in African Americans and whites. Alzheimers Dement 2009;5:445-453. 
 
(10) Mayeda ER, Glymour MM, Quesenberry CP, Whitmer RA. Inequalities in dementia incidence between six 
racial and ethnic groups over 14 years. Alzheimers Dement 2016;12:216-224. 
 
(11) Carter JS, Pugh JA, Monterrosa A. Non-insulin-dependent diabetes mellitus in minorities in the United 
States. Ann Intern Med 1996;125:221-232. 
 
(12) Kurian AK, Cardarelli KM. Racial and ethnic differences in cardiovascular disease risk factors: a systematic 
review. Ethn Dis 2007;17:143-152. 
 
(13) Barnes LL, Leurgans S, Aggarwal NT et al. Mixed pathology is more likely in black than white decedents 
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17 Attachments 
These documents are relevant to the protocol, but they are not considered part of the protocol.  They are 
stored and modified separately. As such, modifications to these documents do not require protocol 
amendments.

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Observational Study Template Version: 5 MAY 2017 
Attachment A Baseline 
Schedule of Events 
 
 
 
Activity 
Visit 1 
 
Visit 2 
 
Visit 3 
Visit 4 
 
Study team procedures 
  
  
  
  
Informed Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Physical Exam 
X 
 
 
 
Height 
X 
 
 
 
Weight 
X 
 
 
 
Vitals signs 
X 
 
 
 
UDS-3 
X 
 
 
X 
Neuropsychological Assessment 
X 
 
 
 
3D-Maze 
 
 
X 
 
Cardiology assessments 
 
 
 
 
 Electrocardiogram 
X 
 
 
 
Laboratory Assessments 
 
 
 
 
SMA-18 
X 
 
 
 
CBC with differential 
X 
 
 
 
HbA1c 
X 
 
 
 
Imaging Assessments 
 
 
 
 
 PET-MR with PiB 
 
 
 
X 
Sleep Studies 
 
 
 
 
Home Sleep Studies 
X 
 
 
 
Nocturnal Polysomnography 
 
X 
X 
X 
 
 
 
 
 
 

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Attachment A 12 month follow-up 
Schedule of Events 
 
 
 
Activity 
Visit 1 
 
Visit 2 
 
Visit 3 
Visit 4 
 
Study team procedures 
  
  
  
  
Informed Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Physical Exam 
X 
 
 
 
Height 
X 
 
 
 
Weight 
X 
 
 
 
Vitals signs 
X 
 
 
 
UDS-3 
X 
 
 
 
Neuropsychological Assessment 
X 
 
 
 
3D-Maze 
 
 
 
 
Cardiology assessments 
 
 
 
 
 Electrocardiogram 
X 
 
 
 
Laboratory Assessments 
 
 
 
 
SMA-18 
X 
 
 
 
CBC with differential 
X 
 
 
 
HbA1c 
X 
 
 
 
Imaging Assessments 
 
 
 
 
 PET-MR with PiB 
 
 
 
 
Sleep Studies 
 
 
 
 
Home Sleep Studies 
 
 
 
 
Nocturnal Polysomnography 
 
 
 
 
 
 
 
 
 

Study #: s18-01302 
 
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CONFIDENTIAL 
This material is the property of the NYU School of Medicine and Langone Medical Center.  Do not disclose or use except as authorized in writing by the study sponsor 
Observational Study Template Version: 5 MAY 2017 
Attachment A Follow-up 
Schedule of Events 
 
 
 
Activity 
Visit 1 
 
Visit 2 
 
Visit 3 
Visit 4 
 
Study team procedures 
  
  
  
  
Informed Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Physical Exam 
X 
 
 
 
Height 
X 
 
 
 
Weight 
X 
 
 
 
Vitals signs 
X 
 
 
 
UDS-3 
X 
 
 
X 
Neuropsychological Assessment 
X 
 
 
 
3D-Maze 
 
 
X 
 
Cardiology assessments 
 
 
 
 
 Electrocardiogram 
X 
 
 
 
Laboratory Assessments 
 
 
 
 
SMA-18 
X 
 
 
 
CBC with differential 
X 
 
 
 
HbA1c 
X 
 
 
 
Imaging Assessments 
 
 
 
 
 PET-MR with PiB 
 
 
 
X 
Sleep Studies 
 
 
 
 
Home Sleep Studies 
X 
 
 
 
Nocturnal Polysomnography 
 
X 
X 
X