Clinical trial NCT04871074
Conditions: Alzheimer Disease
Sponsor: University of Wisconsin, Madison
Start date: 2018-11-18; Completion date: 2025-05-01
Enrollment: 100 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The overarching goal of this project is to use \[C-11\]UCB-J to obtain spatial information on neuronal synapse abundance and inform Alzheimer's disease (AD) progression. The investigators propose to collect longitudinal amyloid, tau, and Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) in participants in the Wisconsin Alzheimer's Disease Research Center (ADRC) and Wisconsin Registry for Alzheimer's Prevention (WRAP) across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive impairment (MCI), and dementia due to AD.

Detailed description:
Synaptic loss is a major feature of symptomatic AD. Conversely, abundance of synapses may confer resilience to cognitive decline in the presence of AD pathology. The pathology-defining features of AD are amyloid plaques and neurofibrillary tangles and their presence and distribution can be spatially estimated in-vivo with amyloid and tau PET. Although these biomarkers can inform on the degree and location of pathology, they do not provide an indicator of their effect on collocated or extended in-network neural damage including synaptic density.

SV2A is expressed ubiquitously in synapses and the capability of assessing SV2A in vivo may provide a direct indicator of synaptic health. Such information would be of high importance for staging the level of synaptic loss or conversely synaptic abundance in the AD continuum and may potentially improve prognostic precision. The PET radioligand \[C-11\]UCB-J is a marker of SV2A.

The overarching goal of this project is to use \[C-11\]UCB-J to obtain spatial information on neuronal synapse abundance and inform upon disease progression. The investigators propose to collect longitudinal amyloid, tau, and SV2A PET in participants in the Wisconsin ADRC and WRAP across the clinical stages of AD, including cognitively unimpaired biomarker negative, unimpaired biomarker positive, MCI, and dementia due to AD.

* Specific Aim 1). Determine the extent to which \[C-11\]UCB-J provides unique information from MRI regarding neurodegeneration. Approach: The investigators will recruit N=60 cognitively unimpaired participants, N=30 MCI participants, and N=30 participants with AD dementia to undergo PET imaging with \[C-11\]UCB-J. MRI will include anatomic and diffusion connectivity MRI. When available, ancillary cerebrospinal fluid (CSF) indicators of neurodegeneration and synapse function will be examined for relationships with UCB-J.
* Specific Aim 2). Determine the rate of synapse loss as reflected by \[C-11\]UCB-J signal across all participants. Rationale: Trajectories of synaptic loss are unknown in vivo. Approach: The investigators will determine the longitudinal trajectories of regional synapse loss that are observed over time among participants who undergo repeat \[C-11\]UCB-J (separated by two years, same participants scanned for Aim 1). The investigators will also examine trajectories by amyloid and tau load. Quantifying longitudinal synaptic loss is expected to eventually facilitate the identification of individuals who are progressing to dementia, as well as inform upon changes that are normal for age.
* Specific Aim 3). Determine the extent to which \[C-11\]UCB-J associates with cognitive decline. Rationale: The investigators expect that lower baseline SV2A density and longitudinal decline in SV2A density in the medial temporal lobe will be associated with faster progression of cognitive decline. The investigators will also test the extent to which harboring multiple pathologies (↑amyloid, ↑tau, and ↓SV2A density) contributes to cognitive decline. Approach: The investigators will examine core indices of cognitive status and continuous measures of cognitive function from the source cohorts and utilize mixed effects models to ascertain the effect of UCB-J amyloid and tau on cognition.
* Specific Aim 4). Determine factors which impact synapse loss. Rationale: Several risk factors for cognitive decline and dementia have been identified including potentially modifiable factors such as insulin resistance and vascular risk factors. Approach: The investigators will determine cross-sectional and longitudinal trajectories of regional synapse loss in relation to risk factors for cognitive decline and dementia. In order to determine insulin resistance, the investigators will perform blood draw and assess fasting glucose and insulin values to determine the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The impact of potentially modifiable risk factors on synapse loss in vivo is currently unknown. This aim will address this gap in knowledge, results which may translate to strategies for reducing dementia risk.

Arms: arm 1: Participants include both cognitively impaired and unimpaired populations to populate a single model to examine variables within the group as a whole.

* Cognitively impaired participants have abnormal cognitive status of MCI or dementia as judged by consensus or expert review using National Institute of Aging and Alzheimer's Association (NIA-AA) 2018 criteria.
* Cognitively unimpaired participants: results of most recent testing with the source cohort indicate the participant is cognitively unimpaired as judged by consensus or expert review.
Interventions: intervention 1: UCB-J intervention 2: MRI Scan intervention 3: PET Scan
Intervention descriptions: intervention 1: PET imaging with UCB-J intervention 2: MRI exams will be performed using a 3T MRI scanner, scan duration is typically 60 minutes intervention 3: PET imaging may be collected using either a PET scanner or a PET/Computed Tomography (CT) scanner, a PET scan will be initiated with the injection of radiotracer

Protocol documents:
Prot_SAP_000.pdf: 
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2018-1283, NCT04871074   
 
SV2A PET Imaging in Alzheimer's Disease 
 
Principal Investigators: 
Barbara Bendlin, PhD 
Brad Christian, PhD 
Sterling Johnson, PhD 
 
Supported by: 
R01 AG062285 (MPI Bendlin, Christian, Johnson) 
 
 
Sponsor of IND: 
Brad Christian, PhD, University of Wisconsin-Madison holds the IND for MK6240 (IND# 134, 516) and 
for SV2A UCB-J (IND# 141177) 
 
Sterling Johnson, PhD, University of Wisconsin-Madison holds the IND for PiB (IND# 177, 114) 


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TABLE OF CONTENTS 
STUDY TEAM ROSTER ...................................................................................................................... 4 
1 
Study objectives ...................................................................................................................... 5 
1.1 
Primary Objectives ...................................................................................................................... 5 
2 
BACKGROUND and Study Context ............................................................................................ 6 
2.1 
Background ................................................................................................................................. 6 
3 
STUDY DESIGN ......................................................................................................................... 7 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS ..................................................................... 7 
4.1 
Inclusion Criteria ......................................................................................................................... 7 
4.2 
Exclusion Criteria......................................................................................................................... 7 
4.3 
Study Recruitment Plan and Enrollment Procedures ..................................................................... 9 
5 
STUDY PROCEDURES .............................................................................................................. 11 
5.1 
Schedule of Evaluations .............................................................................................................. 11 
5.2 
Description of Evaluations and Procedures .................................................................................. 11 
5.2.1 
Screening Evaluation ........................................................................................................................ 11 
5.2.2 
Consenting Procedure ...................................................................................................................... 11 
5.2.3 
MRI Protocol .................................................................................................................................... 12 
5.2.4 
PET Scans ......................................................................................................................................... 13 
5.2.5 
(Optional) Lumbar puncture (LP) ................................................................................................... 155 
5.2.6 
(Optional) FDG ............................................................................................................................... 166 
5.2.7 
Genetic Testing ................................................................................................................................ 16 
5.2.8 
Blood Labs ........................................................................................................................................ 17 
5.2.9 
Neuropsychological testing and assessments, physical and neurological exam .............................. 17 
5.2.10 Consensus Diagnosis (for those not in WRAP or ADRC) ................................................................... 17 
5.3 
Data collection from source study ............................................................................................... 18 
5.4 
Data Banking ........................................................................................................................... 199 
5.5 
Data Sharing .............................................................................................................................. 19 
6 
SAFETY Considerations ........................................................................................................... 20 
6.1 
PET Imaging ([C-11]UCB-J, [F-18]MK6240, [F-18]FDG, and [C-11]PiB radiotracers) ......................... 20 
6.2 
Risks related to disclosure of PET scan results to particpants ........................................................ 20 
6.3 
Adverse Events and Serious Adverse Events Monitoring .............................................................. 21 
6.4 
Follow-up for Adverse Events ..................................................................................................... 22 
7 
STATISTICAL CONSIDERATIONS .............................................................................................. 22 
7.1 
Sample Size Justification ............................................................................................................. 22 
8 
DATA COLLECTION ............................................................................................................... 232 
8.1 
Data Collection Forms ................................................................................................................ 22 
9 
PARTICIPANT RIGHTS AND CONFIDENTIALITY ......................................................................... 22 
9.1 
Institutional Review Board (IRB) Review ..................................................................................... 22 
9.2 
Informed Consent Forms ............................................................................................................ 22 
9.3 
Participant Confidentiality .......................................................................................................... 23 
9.4 
Study Discontinuation ................................................................................................................ 23 


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10 Data Safety Monitoring Plan (DSMP) .................................................................................... 243 
10.1 
Internal Audit and Data Safety Monitoring ................................................................................. 23 
11 Data management tools ....................................................................................................... 243 
11.1 
CoRRIE – CRM database............................................................................................................. 23 
11.2 
PANDA and PACS ...................................................................................................................... 24 
11.3 
BOOKED ................................................................................................................................... 24 
12 PRIVACY .............................................................................................................................. 255 
12.1 
Privacy and Data Storage ........................................................................................................... 25 
12.2 
CoRRIE ...................................................................................................................................... 25 
12.3 
Booked ..................................................................................................................................... 25 
12.4 
PANDA ..................................................................................................................................... 26 
12.5 
REDCap ..................................................................................................................................... 26 
12.6 
FreezerPro ................................................................................................................................. 27 
13 REFERENCES .......................................................................................................................... 28 


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STUDY TEAM ROSTER 
Principal Investigators (MPI): 
Barbara Bendlin, PhD (Contact PI) 
Sterling Johnson, PhD 
Brad Christian, PhD 
Wisconsin ADRC 
Clinical Sciences Center 
600 Highland Avenue, J5/Mezz, Madison, WI 53792 
608-265-2483 
email address: bbb@medicine.wisc.edu 
 
 
Other investigators: 
Charles Stone MD, Nathaniel Chin, MD, Cindy Carlsson, MD 
Sanjay Asthana MD 


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1 
STUDY OBJECTIVES 
Introduction: Synaptic loss is a major feature of symptomatic Alzheimer’s disease (AD) 1. 
Conversely, abundance of synapses may confer resilience to cognitive decline in the presence 
of AD pathology. The pathology-defining features of AD are amyloid plaques and 
neurofibrillary tangles and their presence and distribution can be spatially estimated in-vivo 
with amyloid and tau positron emission tomography (PET). Although these biomarkers can 
inform on the degree and location of pathology, they do not provide an indicator of their 
effect on collocated or extended in-network neural damage including synaptic density. 
Synaptic vesicle glycoprotein 2A (SV2A) is expressed ubiquitously in synapses and the 
capability of assessing SV2A in vivo may provide a direct indicator of synaptic health. Such 
information would be of high importance for staging the level of synaptic loss or conversely 
synaptic abundance in the AD continuum and may potentially improve prognostic precision. 
The PET radioligand [C-11]UCB-J is a marker of SV2A 2-4. The overarching goal of this project is 
to use [C-11]UCB-J to obtain spatial information on neuronal synapse abundance and inform 
upon disease progression. We propose to collect longitudinal amyloid, tau and SV2A PET in 
participants in the Wisconsin ADRC and WRAP across the clinical stages of AD 5, including 
cognitively unimpaired biomarker negative, unimpaired biomarker positive, mild cognitive 
impairment (MCI), and dementia due to AD. 
 
1.1 
Primary Objectives 
Specific Aim 1). Determine the extent to which [C-11]UCB-J provides unique information from 
MRI regarding neurodegeneration. Approach: We will recruit N=60 cognitively unimpaired 
participants, N=30 MCI participants, and N=30 participants with AD dementia to undergo PET 
imaging with [C-11]UCB-J. MRI will include anatomic and diffusion connectivity MRI. When 
available, ancillary cerebrospinal fluid (CSF) indicators of neurodegeneration and synapse 
function will be examined for relationships with UCB-J. 
Specific Aim 2). Determine the rate of synapse loss as reflected by [C-11]UCB-J signal across 
all participants. Rationale: Trajectories of synaptic loss are unknown in vivo. Approach: We will 
determine the longitudinal trajectories of regional synapse loss that are observed over time 
among participants who undergo repeat [C-11]UCB-J (separated by two years, same 
participants scanned for Aim 1). We will also examine trajectories by amyloid and tau load. 
Quantifying longitudinal synaptic loss is expected to eventually facilitate the identification of 
individuals who are progressing to dementia, as well as inform upon changes that are normal 
for age. 
Specific Aim 3). Determine the extent to which [C-11]UCB-J associates with cognitive decline. 
Rationale: We expect that lower baseline SV2A density and longitudinal decline in SV2A 
density in the medial temporal lobe will be associated with faster progression of cognitive 
decline. We will also test the extent to which harboring multiple pathologies (↑amyloid, 
↑tau, and ↓SV2A density) contributes to cognitive decline. Approach: We will examine core 
indices of cognitive status and continuous measures of cognitive function from the source 
cohorts and utilize mixed effects models to ascertain the effect of UCB-J amyloid and tau on 


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cognition. 
 
Specific Aim 4). Determine factors which impact synapse loss. Rationale: Several risk factors 
for cognitive decline and dementia have been identified including potentially modifiable 
factors such as insulin resistance and vascular risk factors. Approach: We will determine cross- 
sectional and longitudinal trajectories of regional synapse loss in relation to risk factors 
for cognitive decline and dementia. In order to determine insulin resistance, we will perform 
blood draw and assess fasting glucose and insulin values to determine the Homeostatic Model 
Assessment of Insulin Resistance (HOMA-IR). The impact of potentially modifiable risk factors 
on synapse loss in vivo is currently unknown. This aim will address this gap in knowledge, 
results which may translate to strategies for reducing dementia risk. 
 
2 
BACKGROUND AND STUDY CONTEXT 
2.1 
Background 
A critical gap in the field is the ability to predict with greater certainty who with AD pathology 
will progress to symptoms, and when. This project will focus on synaptic degeneration as an 
early marker of neurodegeneration and will address important as yet unanswered questions 
regarding the temporal occurrence of synaptic decline in relation to amyloid and tau 
pathology. There are clear implications of such new knowledge from this project in concepts 
relating to brain resiliency as embodied by synapse health, and to improved accuracy of 
cognitive prognosis. 
Synapse loss in AD. Synaptic loss is a key feature of AD, associated with progression from 
healthy cognition to dementia, and preceding neuronal degeneration 6-8. Even early in the 
disease, synapse density is reduced by up to 30%8. Neurogranin, a postsynaptic protein 
primarily localized to the cortex, hippocampus, and amygdala, has been used as a 
cerebrospinal (CSF) biomarker of synapse loss in AD. Using CSF neurogranin, several in vivo 
studies indicate that synapse loss is a feature of dementia and prodromal AD. CSF neurogranin 
levels are elevated in patients with AD and MCI compared to controls 9-11 and this elevation 
appears specific to AD compared to other neurodegenerative diseases 12. Moreover, higher 
CSF neurogranin levels predict conversion from MCI to AD and correlate with a greater rate of 
cognitive decline in MCI 13,14 and older controls 15. While CSF biomarkers may inform upon 
development of AD pathology, they do not provide regional information concerning brain 
areas affected by disease. Regional information obtained in vivo will be especially important 
given mixed literature16-19, and limitations in regional sampling imposed by the logistics of 
post-mortem examination. Imaging measures, such as PET, can inform upon specific regions 
affected by disease, as well as the heterogeneity of disease progression. The temporal 
relationship between the development of amyloid and tau pathology and synapse loss in AD is 
unknown. This project will begin to address this gap in knowledge. 
 
PET imaging of synapses. PET imaging of synapses is a newly developed methodology but 
expected to lead to substantial gains in knowledge of the progression of AD. Development of 
synapse imaging was born out of a medicinal chemistry program to identify antiepileptic drugs 


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with increased affinity at synaptic vesicle glycoprotein 2A (SV2A) which is expressed in 
synaptic vesicles throughout the brain. Research focused on developing PET ligands with high 
SV2A affinity and desirable absorption, distribution, metabolism, and excretion properties led 
to the development of several compounds with favorable in vivo imaging characteristics 3. Of 
these, [C-11]UCB-J is the most recently developed and demonstrates high brain uptake, fast 
kinetics, rapid metabolism, and is safe for multiple administrations3,20. 
 
3 
STUDY DESIGN 
Design: Participants will be recruited to participate in this longitudinal imaging protocol and 
be scanned with [C-11]UCBJ (synapse abundance), [F-18]MK6240 (tau tangles), [C-11]PiB 
(fibrillar amyloid). Additionally, participants will undergo an MRI (if one has not been done in 
the last 12 months), have genetic testing (if not already done with ADRC/WRAP), and 
plasma/serum will be collection for storage. Participants will, also, have the option of 
completing a lumbar puncture and FDG PET scan. Procedures occurring at baseline may be 
repeated approximately 24 months later. See table 1 in section 5: Study procedures. 
 
Patient groups: We will study approximately 120 participants who all fit within two broad 
cognitive groups: 1) cognitively unimpaired, or 2) with cognitive impairment spanning the MCI 
to mild dementia clinical stages due to presumed underlying AD etiology. 
 
Study Location: The entire study including subject recruitment, imaging and analysis will take 
place at the University of Wisconsin-Madison medical campus including the following sites: 
• Waisman Center Laboratory for Brain Imaging and Behavior: where PET and MRI imaging 
will occur as well as analysis. 
• Wisconsin Institute for Medical Research WIMR: where MRI may occur and backup PET 
scanners are located. 
• Alzheimer’s Disease Research Center (ADRC) Imaging Core in the CSC J5/Mezz; K6/3 and 
K6/4 areas of the CSC. At the ADRC Imaging Core, the images will be backed up, 
maintained, and analyzed. 
• Clinical Research Unit: where blood draws and lumbar punctures will be performed. 
• Virtual visits for completing questionnaires, the consent addendum, disclosure, and 
optional disclosure follow up visits, if applicable, may occur via phone call or UW approved 
HIPAA compliant video conferencing software, in addition to UW locations. 
• Dr. Pryzbelski’s clinic: where biomarker disclosure visits may occur 
Enrollment Window and Study Duration: Recruitment and enrollment will require as much as 
2.5 years. Applicable longitudinal imaging may occur about 104 weeks plus/minus 16 weeks 
after baseline imaging. 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1 
Inclusion Criteria 
Cognitively unimpaired adults: 
• Age: Between 55 and 89 


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• Normal Cognition: Results of most recent testing with the source cohort indicate the 
participant is cognitively unimpaired as judged by consensus or expert review 
• General health: Good general health with no conditions/medications affecting cognition or 
imaging 
• Commitment to imaging: Willing to undergo [C-11]UCB-J, [C-11]PIB, [F-18]MK6240 PET 
scans 
• An adequate MRI exam within 12 months prior to baseline. An MRI will be performed if 
not already available. 
Mild Dementia and amnestic Mild Cognitive Impairment 
• Age: 50 years or older 
• Abnormal cognitive status of MCI or dementia as judged by consensus or expert review 
using NIA-AA 2018 criteria5 
• MCIs must be affected in the memory domain but may also have other affected domains 
• Commitment to imaging: Willing to undergo [C-11]UCB-J, [C-11]PIB, [F-18]MK6240 PET 
scans. An adequate MRI exam within 12 months prior to baseline. This MRI exam will 
come from ADRC/WRAP studies. Clinical MRI's (ones obtained outside of our research 
program) will not be adequate. An MRI will be performed if not already available from 
within the research program. 
 
4.2 
Exclusion Criteria 
Candidates meeting any exclusion criteria at screening are not eligible for inclusion: 
• For women: pregnant, lactating or breastfeeding or intention to become pregnant 
• Evidence of unstable or untreated clinically significant gastrointestinal, cardiovascular, 
hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, 
immunodeficiency, pulmonary, or other disorder or disease. Stable, treated chronic 
medical conditions like hypertension, hypercholesterolemia, diabetes mellitus, non- 
metastatic dermatologic or prostatic cancer, etc. are acceptable as long as they do not, in 
the study investigator’s opinion, contribute to cognitive dysfunction or limit participation 
in study procedures. 
• Any illness or other consideration that makes it unlikely that the subject will be able to 
complete the 24-month study 
• Current or prior history (within past 5 years) of significant alcohol or substance abuse as 
determined by the investigator 
• Psychiatric disorders that may interfere with the study including current major Axis I DSM- 
V disorders including but not limited to severe Major depression, current or history of 
bipolar I disorder, or schizophrenia 
• Current use of the anti-seizure medication Levetiracetam, also known as Keppra, Spritam 
or Roweepra 
• Lack of decisional capacity at the time of informed consent 
• MRI exclusion criteria include: 


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o Findings from previous MRIs within the ADRC/WRAP research program that may be 
responsible for neurologic status of the subject such as significant evidence of 
cerebrovascular disease with multiple infarcts, infectious disease, space-occupying 
lesion, normal pressure hydrocephalus, CNS trauma, or any other structural 
abnormality that may impact cognition or image analysis, as judged by the investigator 
o MRI-incompatible implants or devices such as certain cardiac pacemakers or 
defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, 
implanted neural stimulators, CNS aneurysm clips, and other medical implants that 
have not been certified for MRI, or history of claustrophobia in MRI that prevents 
completion of MRI protocol 
• Lumbar puncture exclusion criteria include: 
o Previous lumbar spine surgery 
o Taking blood-thinning anti-platelet medications 
o Taking immunosuppressive medications 
o Being treated or were recently treated for an infection or virus within the last 2 to 3 
months 
 
4.3 
Study Recruitment Plan and Enrollment Procedures 
• Participants may already be in the ADRC clinical core cohort (2015-0030), the WRAP 
cohort (2016-0634), or other relevant ADRC-linked studies. Participants may have had an 
applicable MRI with the ADRC, WRAP, or appropriate linked study. When this is the case, 
we will accept the prior MRI instead of repeating to alleviate subject burden. When 
participants consent to the ADRC clinical core study and WRAP, they agree to be contacted 
about participation in other studies associated with the Alzheimer's Disease Research 
Center or WRAP. Participants may, also, be recruited from the ADRC Registry (2016-0735), 
UW memory clinics, the community, and social media. Subjects will be invited to 
participate via letter, phone, or in-person discussions around the time of their baseline or 
regularly scheduled visit. IRB-approved informational materials may be used. 
• For participants already in an ADRC-linked study, we will conduct database queries and 
screens for participants who meet criteria for controls or patient groups. 
 
• From this general pool, case records will be examined further for eligibility criteria and 
availability of usable MRI. 
o Data reviewed from source protocol records may include memory diagnosis, age, visit 
date(s), sex, race, education level, parental family history of Alzheimer's disease, 
cognitive test results that indicate dementia or MCI, cognitive test results on memory 
and executive function such as list learning, story learning, digit symbol tests, and trails 
tests. Data reviewed may include prior brain imaging and cerebrospinal fluid test 
results that indicate possible risk for dementia, genetic test results such as APOE allele 
carrier status, and other medical history that may affect eligibility for MRI and PET 
imaging such as metal-containing implants, significant neurologic disease or significant 
medical illness. 


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• Candidates who are ostensibly eligible on the record review may be recruited into the 
study in the following ways: 
1. If the participant is not due for an in-person ADRC-linked study in the near future: 
Participants will first be sent a letter in the mail to introduce them to the study. This 
letter will be followed up with a phone call. The screening questionnaire will be 
completed if the participant agrees, and then a study visit will be scheduled in which 
the participant will go over the consent form with a study coordinator. 
 
2. If the participant has an upcoming ADRC-linked study visit: 
The participant will be approached for recruitment at their study visit. They will be 
given a study Information Sheet and will go through the screening questionnaire if 
they agree. If participant would like to take more time to consider, a PET coordinator 
will contact them at a later date. 
 
3. If the participant has an upcoming ADRC or WRAP study visit: 
Participants will be sent a reminder letter in the mail for their upcoming appointment, 
and the letter may include information about this PET scan study opportunity and that 
they will receive more information at their study visit with either WRAP or ADRC. 
Participant may also be approached for recruitment at their WRAP or ADRC study visit. 
 
• Reasons for non-participation of eligible unscreened candidates will be logged. 
 
• Interested candidates will be screened for eligibility using a screening form, either over 
the phone or in person. If all eligibility criteria are met, the participant proceeds to the 
scheduling of a research visit. A screening log will be kept to record reasons for screen 
failures. 
 
• Women of childbearing potential will have a urine pregnancy test within 24 hours prior to 
undergoing each PET scan. The test must be negative to proceed with the scan. 
• Informed consent will be required prior to procedures. Only individuals with capacity to 
consent will be included. Our center has procedures built into the IRB approved 
consenting process to ensure participants have capacity to consent. 
• Exceptions to eligibility criteria are rare but may occur at the discretion of the principal 
investigators. For example, exceptions may be made related to a participant’s potentially 
confounding data. Exceptions will not be made related to a participant’s safety. 


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5 
STUDY PROCEDURES 
5.1 
Schedule of 
Evaluations 
See Table 1. 
Completion of study 
procedures at 
baseline and 
potential follow-up 
visits will take 1-4 
days depending on 
procedures due and 
the schedules of 
participants, staff, 
and facilities. 
5.2 
Description of 
Evaluations and 
Procedures 
5.2.1 Screening Evaluation 
Screening 
assessment: After 
appropriate subjects 
are identified who 
meet study criteria, 
they will be 
contacted by phone 
or mail by trained 
study coordinators 
and invited to 
participate. A 
screening discussion 
will be completed on 
the phone or in 
person. The 
screening is done to 
determine whether 
the participant continues to meet all study inclusion and none of the exclusion criteria and 
assess eligibility for MRI if applicable. 
5.2.2 Consenting Procedure 
Before any study procedures are performed, informed consent will be obtained. A single 
consent form and process will be used. The study coordinator or one of the study 
Table 1. Overview of study design and timeline 
Screening by Staff 
Baseline 
24 months 
Prior to baseline 
0 weeks (day 0) 
104 weeks (±16 weeks) 
Medical history, 
medication review, 
eligibility determination 
Review of medical/surgical 
history, medications, allergies, 
family history 
Review of medical/surgical 
history, medications, allergies, 
family history 
MRI (if not available within 12 
months) 
MRI (T1, T2, DTI) 
[11C]PiB PET 
[11C]PiB PET 
[18F]MK-6240 PET 
[18F]MK-6240 PET 
[11C]UCB-J PET 
[11C]UCB-J PET 
[18F]FDG PET (optional) 
[18F]FDG PET (optional) 
Lumbar puncture (optional) 
Lumbar puncture (optional) 
CDR interviews and NPI-Q, GDS, 
FAS, IQCODE questionnaires (if 
not done with ADRC/WRAP) 
CDR interviews and NPI-Q, GDS, 
FAS, IQCODE questionnaires (if 
not done with ADRC/WRAP) 
Diabetes questionnaire 
Diabetes questionnaire 
Genetic testing (if not done with 
ADRC/WRAP) 
Genetic testing (if not done with 
ADRC/WRAP) 
Blood draw: 
1. Plasma and Serum: all 
participants 
2. Glucose and insulin: all 
participants unless performed 
by parent study (ADRC or 
WRAP) in last 6 months 
3. Whole blood for ApoE: only 
community/clinic participants 
Blood draw: 
1. Plasma and Serum: all 
participants 
2. Glucose and insulin: all 
participants unless performed 
by parent study (ADRC or 
WRAP) in last 6 months 
3. Whole blood for ApoE: only 
community/clinic participants 
Physical and Neurological Exam 
(community/clinic participants or 
those participating in LP) 
Physical and Neurological Exam 
(community/clinic participants or 
those participating in LP) 
Neuropsychological testing 
(community/clinic participants): 
MoCA, Craft Story (recall 
immediate & delayed, Benson 
Complex Figure Copy (immediate 
& delayed), Number Span test 
(Forward & Backwards), Category 
Fluency (Animals & Vegetables), 
Trails Making Test (A & B), MINT 
(Multilingual Naming test), Verbal 
Fluency: Phonemic Test (F,L & C), 
RAVLT– Version 2 (Immediate, 
Delayed & Recognition tasks), 
WAIS-R Digit Symbol 
Neuropsychological testing 
(community/clinic participants): 
MoCA, Craft Story (recall 
immediate & delayed, Benson 
Complex Figure Copy (immediate 
& delayed), Number Span test 
(Forward & Backwards), Category 
Fluency (Animals & Vegetables), 
Trails Making Test (A & B), MINT 
(Multilingual Naming test), Verbal 
Fluency: Phonemic Test (F,L & C), 
RAVLT– Version 2 (Immediate, 
Delayed & Recognition tasks), 
WAIS-R Digit Symbol 
Disclosure of PET scan results (if 
consented) 
Disclosure of PET scan results (if 
consented) 


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investigators will obtain written informed consent, and the original document is stored in 
each participant’s study binder/folder. The coordinator will review the consent form with 
participants at the study visit in person. Once review is complete, an assessor will either 
provide a capacity assessment in person or via phone/internet. Consent and capacity will 
therefore take place at the same time. 
 
Participants who would like to know their amyloid result will also complete the consent 
addendum for disclosure of PET scan results. The consent addendum may be completed in 
conjunction with the main informed consent or after initial study consent and visits if they 
would like more time to consider the option or would like to opt in after previously opting out 
of disclosure in the informed consent. The consent addendum may be conducted in-person, 
via phone call, or via UW approved HIPAA compliant video conferencing software. If the 
consent addendum is not completed in person, participants will be instructed to electronically 
sign the document via an FDA Part 11 compliant software. If the participant is unable to 
electronically sign the consent, the participant will be instructed to mail the signed consent to 
the study team. In instances of remote consent, in which the study is not able to witness the 
signing of the consent, the study team will verify the identity of the signer by confirming 
personal information such as date of birth and current address. Capacity assessment will be 
completed by study clinician or nurse practitioner for individuals with dementia, as applicable, 
before a participant with dementia consents to disclosure of results with the consent 
addendum. If the capacity assessment indicates that the participant lacks decision-making 
capacity at this point, the participant’s assent and surrogate consent may be obtained. 
 
5.2.3 MRI Protocol 
If the participant otherwise meets all inclusion and no exclusion criteria, the MRI will be 
performed if a suitable scan is not available from approximately the prior 12 months to 
baseline from an affiliated study. If participants report a possible history of metal in their eyes 
or a history of working with metal (grinding, welding, etc.), they will receive an orbital x-ray to 
ensure eligibility for MRI. This procedure includes a T1-weighted anatomic volume, a T2- 
weighted fluid attenuated inversion recovery (FLAIR) scan, and diffusion imaging. These 
sequences do not take the place of a clinical MRI examination. If clinically significant 
abnormalities are found, the participant is excluded and referred for further clinical follow-up. 
 
The MRI exams will be performed using a 3T MRI scanner at the Waisman Center or WIMR. 
The scan duration is typically 60 minutes and no longer than 75 minutes and consists of 
established as well as innovative locally developed scan sequences. Participants are asked to 
fast 4 hours prior to MRI. 
The MRI procedure is considered complete if a T1-weighted volume, FLAIR, and DWI scan are 
successfully acquired. When feasible, additional scans will be acquired. The additional 
sequences will make it possible to conduct exploratory comparisons. Sequences may include: 


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T1w Brain Volume: This sequence provides high-resolution volume and region quantification. 
This sequence is required and used for quantifying the PET images. 
T2 Fluid attenuated inversion recovery (FLAIR): This is a 3D volume acquisition and is 
sensitive to ischemic disease and other pathology. This scan will be used to quantify white 
matter hyper-intensity lesion burden. 
 
Diffusion Imaging: A diffusion-weighted may be performed used for whole brain advanced 
DTI studies. Diffusion encoding will be performed using multiple shells and multiple directs 
requisite for NODDI and advanced DTI modeling of white matter tracts. 
 
Other non-required MRI sequences: Additional sequences from the ADRC/WRAP standard 
protocol may be used to maintain continuity with prior and future MRIs with the program. 
These are performed when time schedule and tolerability permit and will be used to conduct 
exploratory analyses. 
Quantitative T1 Mapping with MPNRAGE: This is a locally developed anatomical sequence for 
detailed T1-mapping and tissue segmentation. This is a non-standard sequence conducted in 
Research mode. 
 
Pseudo-continuous arterial spin labeling (pCASL): This provides a perfusion weighted scan 
used to assess flow and aspects of neurovascular function. 
 
4D flow: We will use a novel high-resolution flow-sensitive MRI approach to quantify 
macroscopic CBF in all extracranial and intracranial arteries in a single acquisition. The method 
developed at UW uses radial undersampling and significantly reduces otherwise prohibitively 
long scan times for a vascular examination uses no exogenous contrast agent. The method 
allows for coverage of the entire brain, providing high spatial resolution and flow dynamics 
within an approximately 7-minute exam. This is a non-standard sequence conducted in 
Research mode. 
5.2.4 PET Scans 
PIB: The synthesis and PET scanning with [C-11]PiB will be consistent with the methods 
described in the drug IND. A target dose of 8-15 mCi +/- 10% of PiB bolus is injected over ~30 
second infusion with the participant positioned in the scanner. A 70 minute dynamic PET scan 
will be initiated with the injection of radiotracer. An alternative abbreviated imaging session 
of 50-70 minutes post-injection may be used if the participant is unable to complete a full 70 
minute scanning procedure. If an acceptable PiB scan conducted with our research program is 
available within approximately 12 months of baseline, this scan will not be repeated. 
MK6240: The synthesis and PET scanning with [F-18]MK6240 will be consistent with the 
methods described in the drug IND. A target dose of 5-10 mCi +/- 10% of MK6240 bolus is 
injected over ~30 second infusion. Uptake occurs at rest for approximately 70 minutes 


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followed by imaging across the interval of approximately 70 to 110 minutes from time of 
injection (thus, approximately 40 minutes of imaging). A 20-minute frame within this window 
will be considered sufficient for a successful scan. If an acceptable tau scan conducted with 
our research program is available within approximately 12 months of baseline, this scan will 
not be repeated. 
 
UCB-J: The synthesis and PET scanning with [C-11]UCB-J will be consistent with the methods 
described in the drug IND. A target dose of 5-15 mCi +/- 10% of UCB-J bolus is injected over 
~30 second infusion with the participant positioned in the scanner. A 70 minute dynamic PET 
scan will be initiated with the injection of radiotracer. An alternative abbreviated imaging 
session of 40-70 minutes post-injection may be used if the participant is unable to complete a 
full 70 minute scanning procedure. If an acceptable UCB-J scan conducted with our research 
program is available within approximately 12 months of baseline, this scan will not be 
repeated. 
 
If there is any tracer synthesis failure, we will reschedule the visit to a later date. 
 
PET Scanner: PET imaging may be collected using either a PET scanner or a PET/CT scanner, 
depending on scanner availability. Participants are positioned headfirst and supine with the 
canthomeatal line parallel to the in-plane field of view. The CT or a transmission scan is 
acquired for attenuation correction. 
 
It is possible that this scan will need to be repeated (whether a chemistry issue arose, there 
was a problem with the scan itself, etc.). An additional CT transmission scan contributes a 
radiation dose of 0.2mCv, which is less than 1% of the dose received from the entire protocol. 
 
Blood pressure: A participant’s blood pressure will be taken before and after each PET scan 
they participate in. 
Disclosure of Biomarker findings to participants: Amyloid PET scan results may provide 
important helpful information pertinent to a person’s diagnosis, clinical care, and personal 
planning goals. Results of amyloid PET may be disclosed to participants who consent to this 
and who want to know their results by a trained clinician with expertise in 
dementia/geriatrics. Study staff will contact participants to determine their interest in 
learning their amyloid results with a phone call and follow up with a letter, if needed. The 
study staff will provide and review an educational pamphlet and/or educational PowerPoint 
slides. They will also conduct psychological screening assessments and a pre-disclosure semi- 
structured interview to gauge the emotional readiness of the participant to receive these 
results and to ensure safety after disclosure of results which may include the following: PHQ-4 
(Patient Health Questionnaire – 4), C-SSRS (Columbia-Suicide Severity Rating Scale), 
Alzheimer’s Disease Suicide Questionnaire, and INI-AD (Impact of NeuroImaging in 
Alzheimer’s Disease; completed post-disclosure). If the psychological screening assessments 


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exceed set thresholds, the study team will determine if the participant will either be excluded 
from disclosure or re-screened at a later date by a clinician prior to disclosure. 
These assessments are only applicable for disclosure of PET scan results to participants. If 
during any of the participant interactions (whether in person, by phone, or video 
conferencing) the participant expresses concerns, hopelessness, or suicidal ideation, the study 
coordinator will involve relevant clinical expertise to address participant concerns and issues. 
Follow up will be initiated by the clinical team when warranted. Participants that exceed set 
thresholds or do not have emotional readiness at clinician’s discretion will be excluded from 
the disclosure procedure. Participants will be made aware that a study coordinator or clinician 
will provide a follow-up phone call approximately 24-72 hours post-disclosure to follow up 
and address any further questions or concerns. Any concerns will be immediately followed up 
by a study clinician. Participants may be provided with referrals for mental health treatment 
or encouraged to follow-up with their primary care provider. We are equipped to handle 
potential negative effects from disclosing amyloid status; however, we anticipate that, similar 
to other studies, any negative effects will be mild and temporary. 
The disclosure of PET results occurs within approximately 12 months of PET scanning visits or 
consenting to the disclosure process. The disclosure will be completed in-person or via UW 
approved HIPAA compliant video conferencing software by an experienced clinician, 
practitioner, or social worker within the ADRC research program. This role will be documented 
in the delegation of duties log. Standardized talking points will be followed for the disclosure, 
and the participant will be offered support including clinical referrals as needed, a follow-up 
letter reiterating the results, and any recommendations, and informing the participant’s 
physician if requested. Participants will be offered optional supportive follow up visits, 
including a session to discuss lifestyle/risk reduction and/or a session to review community 
resources and referrals, and participants will be provided with an optional satisfaction 
measure for quality improvement purposes. 
 
Due to the recent progress of anti-amyloid therapies, participants with a diagnosis of MCI or 
dementia and with a positive amyloid PET scan may now receive those results at anytime. PET 
result disclosure may occur with participants who received their PET scan under the ADRC, 
WRAP, an ADRC-affiliated study, or a WRAP-affiliated study when disclosure under the 
protocol conducting the scan isn’t feasible (e.g. the protocol is in data analysis) 
 
5.2.5 (Optional) Lumbar puncture (LP) 
Participants who agree to this procedure will have cerebrospinal fluid (CSF) acquired via LP at 
baseline (if no sample from the past 18 months is available) and at the end of the potential 2- 
year follow-up (if no sample from the past 18 months is available). An experienced clinician 
will collect CSF on all willing and eligible participants according to well-established procedures 
and the infrastructure of the ADRC. The procedure will be done in the Clinical Research Unit 
(CRU) after a 4 hour fast. Though, exceptions to the fasting requirement may be made on a 
case-by-case basis in consultation with a study clinician or PI. 


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All CSF collection is completed according to the guidelines put forth in the “Biospecimens Best 
Practice Guidelines for the ADCs” published by the National Alzheimer’s Coordinating Center 
(NACC) and available on their website. CSF collection occurs at approximately the same time 
at each visit to help control for diurnal variability. LPs will be performed using Sprotte spinal 
needles, drip method and/or gentle extraction technique. Participants are placed in the sitting 
position and asked to maximally flex their knees, hips, back, and neck. The skin over the L3-L4 
or L4-L5 vertebrae is prepped. 1% lidocaine is used as a local anesthetic, followed by insertion 
of a spinal needle with an introducer into the L3-L4 or L4-L5 interspace using sterile technique. 
Approximately 25 mL of CSF will be collected using sterile polypropylene collection tubes. 
Fresh CSF will be analyzed on the Roche analyzer in-house, and the remainder of the extracted 
CSF will be aliquoted, frozen, and stored as usual for future assays. 
 
Vitals will be taken at any CRU visit. 
CSF samples may be sent to Dr. Henrik Zetterberg—an internationally recognized leader in CSF 
biomarker analysis—at his laboratory at the Sahlgrenska Hospital Goteborg University in 
Sweden as a fee-for-service analysis. (APOE genotyping will not be shared outside). All 
samples will be coded with a unique identifier to keep the laboratory blinded to factors such 
as subject identity or group. 
 
CSF samples will also be released to the University of Bristol, Dementia Research Group, 
Bristol, England (Dr. Scott Miners). Dr. Miner’s lab will be running new assays to look at 
Alzheimer’s disease and vascular markers. 
 
CSF samples, along with plasma and serum, may also be sent to the Center for Biomedical 
Research, Ulm, Germany (Dr. Patrick Oeckl) for measurement of markers related to Synapses. 
Samples will be coded with a unique identifier to keep the laboratory blinded to factors such 
as subject identity or group. 
 
5.2.6 (Optional) FDG 
Participants are studied after an approximately 4hr fast (water is allowed). The blood sugar 
will be tested (via finger puncture) before an FDG PET scan. Following the 5 mCi (± 20%) 
injection with [F-18]FDG compound, participants rest in a quiet room. Imaging begins 
approximately 30 minutes post injection and takes place over an interval of 30 minutes. Our 
team has obtained PET images for several NIH funded protocols (including the Alzheimer’s 
Disease Neuroimaging Initiative), and thus we are experts in obtaining both of these scans. 
Amyloid, tau and synaptic density PET images will not typically be clinically evaluated as the 
clinical relevance of a positive scan is yet unknown. Approximately 30% of cognitively healthy 
individuals are amyloid positive, and the diagnostic relevance of a positive scan is yet to be 
determined. FDG-PET scans will not typically be evaluated by a clinician because the clinical 
utility of this scan in a healthy participant is not known. FDG is an FDA approved tracer; 
however, this is being used outside of its clinical labeling indications as it is being used for 
research purposes only. 


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5.2.7 Genetic Testing 
Genetic testing (for the APOE gene) will be conducted on participants who have not had this 
testing with the ADRC. The result of this test will not be shared back with the participant. 
Blood will be drawn from subjects for the purpose of genotyping various SNP sequences, 
including Apolipoprotein E (ApoE), at their baseline visit only (who do not have this 
information on file). Genotyping will be performed on batches of stored samples of DNA 
extracted from buffy coat derived from blood collected at baseline. Buffy coat and DNA not 
used for genotyping will be stored for future use. Results of this genotyping will not be 
reported to subjects, nor will it be included in their medical records, as the results of this 
genotyping do not yet aid the participant in future treatment options. 
5.2.8 Blood Labs 
Blood plasma and serum will be collected from all participants to be stored for future research 
to look at markers for AD risk factors. Additionally, fasting glucose and fasting insulin will be 
tested if not already completed by the WRAP/ADRC study the same day. Blood will still be 
drawn if the participant is not fasting. Both procedures will be done at baseline and the 
potential follow-up to allow for the analysis of changes that occur over time. This procedure 
will be done at CRU. 
 
5.2.9 Neuropsychological testing and assessments, physical and neurological exam 
Participants who have not undergone neuropsychological testing or physical/neuro exams 
with the WADRC or WRAP or participant, such as those who are recruited from the memory 
clinic or community, will be required to do so with this study at baseline and the potential 
follow up visit. The neuropsychological testing will consist of a multidimensional set of brief 
measures assessing cognitive, emotional status that can be used as a “common currency” 
across diverse study designs and settings. These will be supplemented by measures that are 
consistent with other national studies of AD, such as the NIH-funded Alzheimer's Disease 
Neuroimaging Initiative (ADNI). Participants will also complete: MoCA, Craft Story (recall 
immediate & delayed), Benson Complex Figure Copy (immediate & delayed), Number Span 
test (Forward & Backwards), Category Fluency (Animals & Vegetables), Trails Making Test (A 
& B), MINT (Multilingual Naming test), Verbal Fluency: Phonemic Test (F,L &C), RAVLT– 
Version 2 (immediate, delayed & recognition tasks ), and WAIS-R Digit Symbol. 
 
For completion of certain assessments, such as the Clinical Dementia Rating [CDR] Scale and 
IQCode, a family member or a friend will be asked to provide information via the telephone. 
 
All tests will be given by trained personnel and will be standardized for reliable 
administration. In some cases, the tests may be audio-recorded to make sure we accurately 
document the participant’s responses. 
 
Physical and neurological exams will be completed by ADRC clinicians. Information on family 
history, medical/surgical history, medications, and allergies will be collected from participants 


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from the community, memory clinic, or those without current information with WRAP or 
ADRC. Participants will be provided forms at a visit. Forms can be completed at a visit, after a 
visit by phone, or at home then returned by mail. 
 
5.2.10 Consensus Diagnosis (for those not in WRAP or ADRC) 
After each study visit, our expert clinician(s) and research staff will meet to review the 
information we collect about the participants and give their opinion about their diagnostic 
status. In this meeting, all data will be reviewed from all participants including those with 
Alzheimer’s disease, mild cognitive impairment, and the healthy older controls. Participants’ 
diagnostic status will be reviewed after every study visit since cognitive function might 
change year after year. No matter the cognitive status, if the memory tests performed in 
this study reveal something unexpected that is of clinical concern, a study team clinician, 
with expertise in diagnosing memory disorders, will contact the participant by phone to 
discuss the results and refer them for clinical evaluation. 
5.3 
Data collection from source study 
This study recruits from WRAP, ADRC, the ADRC Registry, UW memory clinics, linked studies, 
and the community. Relevant information from those sources will be obtained for analysis 
under this protocol. Data collected will be both retrospective and prospective. Information to 
be collected includes the following: 
 
• Cognitive data including all relevant psychometric assessments and alpha-numeric results 
from serial cognitive assessments. Cognitive test results may indicate dementia or MCI. 
Data collected also includes cognitive test results on global cognitive tests, memory, and 
executive function such as list learning, story learning, digit symbol tests, and trails tests. 
Rationale: Using these collected data will facilitate analysis of relationships between 
disease burden and the presumed cognitive effects. 
 
• Clinical data including diagnostic consensus conference summaries. Primary diagnoses 
(such as MCI or dementia due to AD) and any relevant secondary diagnoses (such as 
vascular disease) would be captured. Rationale: Diagnosis is a main grouping variable. 
 
• CSF lab test results if participants have provided CSF. We will access the results of those 
tests. Values will include AD-related assays such as tau and amyloid, inflammation assays 
such as YKL40, neurodegeneration assays such as neurogranin and neurofilament light, 
and other proteins that are relevant to synapse loss, aging, and Alzheimer’s. Rationale: 
These assays are used to cross-validate the molecular PET scans. 
 
• Prior imaging such as existing MRI, PIB and MK6240 images. They will be utilized in 
analyses. Rationale: Reduce participant burden, minimize exposure to procedures and 
radiation (e.g., repeating an MRI or PET scan) when existing data is already available, and 
evaluate longitudinal change in amyloid and tau burden. 


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• Questionnaire data including previously and prospectively collected self-report and 
informant report data from ADRC and WRAP, such as symptom checklists and surveys 
such as clinical dementia rating, quick dementia rating scale, informant questionnaire on 
cognitive decline in the elderly (IQCODE) and independent activities of daily living (IADL). 
May also include survey results such as sleep surveys, diet surveys, and physical or 
cognitive activity surveys. Rationale: These questionnaires provide support for diagnostic 
groups and provide an index of symptom severity and resiliency. 
 
• Genetics including APOE genetic status. Rationale: APOE4 is a risk factor for AD and will be 
analyzed as a predictive marker. 
5.3.1 Visit Sharing 
Participants in this study are also eligible to enroll in LEAD, ALERTT, LIFE, PREDICT3 and the 
ADRC/WRAP PET Study. To reduce participant burden, visits may be shared with other 
studies. In other words, participants may complete more than one study during a single visit. 
Subjects who enroll in Synapse and ALERTT, PREDICT3, ADRC/WRAP PET Study, LEAD, LIFE, 
ADRC, or WRAP may undergo shared study visits, in which the relevant collected information 
will be analyzed in both studies. The synchronization of study visits will be handled by each 
protocol’s primary study coordinator. PET imaging data will be shared amongst studies to 
reduce the PET imaging burden placed on participants. We will not repeat a PET scanning 
procedure if a participant has recently had a tau or amyloid PET scan with another study. 
Participant comfort is assessed at regular intervals. The results of lab tests will be shared 
across protocols. This will reduce subject burden. Only data and samples approved for 
collection under the other study’s protocol will be transferred from this study. Likewise, only 
data and samples approved for collection under this protocol will be transferred from the 
aforementioned studies. Study coordinators of the other protocol will be listed as key 
personnel on this study. Participants will be enrolled and consented for all studies that are 
conducted at the shared visit. Study staff from those protocols will already have access to this 
study’s code-name links. As a step to protect confidentiality, data and samples will be labeled 
with study ID numbers and not names. 
 
5.4 
Data Banking: 
Data banking is a required component of the study; participants must agree to data banking at 
the time of consent. Participants may request to have their data withdrawn from the bank, 
and then, study personnel will remove their data from the bank and will discontinue using it 
for further research. Data collected from this study will be stored on Department of Medicine 
computer servers that are password-protected. Banked data is coded with a subject ID. Only 
approved study personnel have access to the key linking subject ID and identifiable subject 
information. Unless staff are listed as key personnel on this study, they will not be given 
access to the code linking subject identity with subject ID. 


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5.5 
Data Sharing: 
Banked images and their meta-data from this study will be managed by the ADRC imaging 
core. Images may be uploaded to the National Alzheimer’s Coordinating Center or other NIH- 
specified repository. The images will be shared back with the ADRC UP protocol (2013-0178), 
the ALERTT study (2018-1348), the ADRC, and WRAP to address the major specific aims of this 
project. Once the data is shared with the ADRC UP protocol, the data may be used to address 
future unspecified research. Other investigators who wish to use these data may contact Dr. 
Bendlin, and she will collaborate with Dr. Christian and Dr. Johnson to decide how the data 
from this study are shared. Investigators from other departments within UW, institutions 
outside UW, and private companies may contact Dr. Bendlin and request the data. Only coded 
data are shared with researchers that are not listed as key personnel on the projects. The 
multi-PIs (Bendlin, Christian, Johnson) hold ultimate responsibility for data sharing oversight 
and will review all requests. 
 
Coded images and AE data pertaining to MK6240 will also be sent to Cerveau Technologies, 
Inc., the provider of the MK6240 drug precursor. Cerveau will use these data for image quality 
assurance and drug safety profile tracking. Cerveau maintains safety data for all sites using the 
MK6240 drug and is responsible for Investigational Drug Brochure updates. In addition to 
images, Cerveau will have access to brain MR images, unique subject identifiers, amyloid 
images and status, cognitive metrics consisting of MMSE, ADAS-COG and CDR, weight/height, 
scan time, MK6240 dose, scan date, clinical diagnosis, demographic information, and smoking 
status. 
 
Cerveau will provide secure storage of the study data described above, be responsible for 
transferring MRI and PET images, perform Image data quality control, and ensure consistent 
image acquisition and transfer via an electronic image submission system. The electronic 
image submission system is in compliance with 21 CFR Part 11, electronic records, electronic 
signatures and predicate rules. Compliance is achieved through a combination of SOP 
adherence and a structured validation system. Security of this system includes the use of 
passwords that limit user access according to their job responsibilities. Throughout the study, 
an image data back-up will be performed on data storage systems. Off-site image data back- 
up will also be performed. Other electronic data (electronic CRFs, audit trails, database 
contents, electronic documents, etc.) will be stored on a dedicated database server and saved 
daily throughout the study. Access to the data at the clinical site is restricted to authorized 
personnel only. 
 
6 
SAFETY CONSIDERATIONS 
6.1 
PET Imaging ([C-11]PiB, [F-18]MK6240, [C-11]UCB-J, and [F-18]FDG radiotracers) 
Radiation exposure: PET Imaging ([C-11]PiB, [F-18]MK6240, [C-11]UCB-J, and [F-18]FDG 
radiotracers) involves exposure to small amounts of ionizing radiation, which has no known or 
expected harmful effects. The possibility exists for a rare reaction to any of the substances or 
procedures to which the subject is exposed. 


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People who live in the US receive on average a total of 6.4 mSv per year. 50% (3.2 mSv) comes 
from natural background sources (e.g., food we eat, air we breathe) and 50% (3.2 mSv) from 
human sources (e.g., dental and medical exams). 
 
This study consists of up to 8 PET scans including 4 at baseline and 4 at the potential 2-year 
follow up. The scans may take place on a PET/CT or just PET machine. The radiation dose 
calculations include the low dose CT procedure. 
C-11 PiB brain scan (2.9mSv at each of two scans = 6.8mSv) 
F-18 MK-6240 brain scan (12 mSv = 24 mSv) 
C-11 UCB-J brain scan (2.0 mSv at each of two scans = 4.0 mSv) 
F-18 FDG brain scan (4.2 mSv at each of two scans- 8.4 mSv) 
 
The four scans together = 42 mSv total potential exposure over the two-year study (baseline 
and potential follow-up). This is below the guidelines established in 21CFR §361.1 for 
occupational whole body (Annual Limit - 50 mSv) exposure. 
6.2 
Risks related to disclosure of PET scan results to participants 
Although several studies suggest minimal acute psychological consequences to disclosure of 
beta-amyloid results or other AD risk information, there is a risk of increased depression, 
anxiety, or potential for suicidality associated with learning beta-amyloid results. Additionally, 
there is a risk that participants will make decisions based on beta-amyloid results that impact 
other psychosocial outcomes (e.g., financial/retirement plans, long-term care plans) that will 
take longer to fully evaluate. There is a risk that beta-amyloid results will be shared by 
participants with individuals who are also impacted by the information regarding risk for 
development of AD, such as family members. If that happens, there could be consequences 
(emotional, stigma etc.) for both the participant and recipient of the information. It could 
affect relationships with family and friends, affect employment, or make it harder to get 
insurance or a job. Although we will not add study information to medical records, we will 
communicate results to providers at the participants’ request, and it is possible that 
participants could share the information with their healthcare providers who may add it to 
their medical record. Participants will be informed that this has the potential to impact long- 
term care insurance applications or other unforeseen consequences regarding medical care. 
We will ensure that a number of safeguards are in place to protect participants from any 
serious, negative effects of disclosure such as completing the psychological screening 
assessments to assess depressive symptoms, anxiety, and suicidality, the pre-disclosure 
questions, the post-disclosure questions, providing follow up, and offering optional follow-up 
support visits to discuss lifestyle/risk reduction and/or community resources and referrals. 
Participants that exceed set thresholds or do not have emotional readiness at the clinician’s 
discretion will be excluded from the disclosure procedure. 


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6.3 
Adverse Events and Serious Adverse Events Monitoring 
The PIs will be apprised of any adverse events and will report any SAEs experienced in the 
study to the IRB. Although no study related serious adverse events or significant trends have 
been reported in the combined experience of our institution and other institutions for either 
radioligand, we will examine AEs for study related trends. If needed, we would modify the 
consent form after consulting with the CTRC Research Subject Advocate and the IRB. 
 
Vitals are assessed prior to and after the PET scans. The participant is given the study team’s 
contact information so that they may report any adverse events that may occur within the 
next 24 hours. If any adverse events are discovered, a clinician will continue to follow up with 
the participant until resolved. 
 
An adverse event (AE) is any unfavorable and unintended diagnosis, symptom, sign (including 
an abnormal laboratory finding), syndrome, or disease which either occurs during the study 
(having been absent at baseline) or, if present at baseline, appears to worsen. Adverse events 
will be recorded regardless of their relationship to the study. 
A serious adverse event (SAE) is generally defined as any untoward medical occurrence that 
results in death, is life threatening, requires inpatient hospitalization or prolongation of 
existing hospitalization, results in persistent or significant disability/incapacity, or is a 
congenital anomaly. 
 
Participants will be advised to inform us of any adverse events following PET scans. 
 
6.4 
Follow-up for Adverse Events 
The investigator is obliged to follow subjects with AE’s until the events have subsided, the 
conditions are considered medically stable, or the participants are no longer available for 
follow up. Subjects who discontinue due to adverse events will be treated and followed 
according to established medical practice. 
7 
STATISTICAL CONSIDERATIONS 
7.1 
Sample Size Justification 
Approximately 120 participants will be enrolled. This will provide a sufficient number of cases 
to achieve the aims described above. 
Prospective power was estimated using MedCalc version 18.2.130. Assuming an AUC of 0.73 
for discriminating MCI and Control participants 31, and a correlation of 0.77 between synaptic 
density and cognition 32, with our proposed sample of NMCI=30 and NCtrl=60, we will have 80% 
power to detect a 10% improvement in AUC with [C-11]UCB-J. A sample of 30 participants 
with dementia due to AD will be imaged to obtain qualitative information concerning synapse 
density loss in phenotypic and biomarker confirmed disease. 


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8 
DATA COLLECTION 
8.1 
Data Collection Forms 
The study coordinator works with the participant at the study visit to collect all relevant data. 
Case report forms will be generated to record the data. CRFs and all participant specific data 
are stored hard copy in an individual binder/folder. 
 
9 
PARTICIPANT RIGHTS AND CONFIDENTIALITY 
9.1 
Institutional Review Board (IRB) Review 
This protocol and the informed consent document and any subsequent modifications will be 
reviewed and approved by the University of Wisconsin-Madison Health Sciences IRB. 
 
9.2 
Informed Consent Forms 
A signed consent form will be obtained from each participant. The consent form will describe 
the purpose of the study, the procedures to be followed, and the risks and benefits of 
participation. A copy will be given to each participant and this fact will be documented in the 
participant’s record. Only participants with cognitive capacity to provide consent will enroll in 
this study. 
 
This study enrolls participants with cognitive capacity, but it cannot be predicted in advance 
who will lose decision-making capacity over the course of the study. We need to enroll those 
who are at risk for losing capacity to determine if the synaptic density significantly varies or 
changes at this stage in the disease. The longitudinal study aims require collecting data on 
synapse density at time points two years apart. 
If the subject has lost capacity to consent during the study, we would request a surrogate to 
re-consent in their place. Surrogates may include a court appointed guardian or next of kin (in 
the order of priority): spouse, adult child (18 or older), parent, adult sibling, grandparent, or 
adult grandchild. If surrogate consent is required, the consent form will be modified to specify 
surrogate consent and instruct surrogates that their decisions should be based on what the 
surrogate believes would be desired by the subject. If that cannot be determined, the 
surrogate would decide based upon what s/he believes is in the subject’s best interest. 
 
9.3 
Participant Confidentiality 
Any data, forms, reports, PET images, and other records will be identified with minimum PHI 
necessary. A participant ADRC identification number (Participant ID, PID) is used to maintain 
confidentiality, and the key to the ID code is never released outside the study team. All 
records will be kept in a locked file cabinet. All computer entry and networking programs will 
be done using PIDs only. Identifying information will not be released without written 
permission of the participant, except as necessary for monitoring by IRB, the FDA, the NIA, 
and the OHRP. 
9.4 
Study Discontinuation 
The study may be discontinued by the IRB, the NIA, the OHRP, the FDA, or other government 


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2018-1283, NCT04871074   
 
agencies as part of their duties to ensure that research participants are protected. 
 
10 
DATA SAFETY MONITORING PLAN (DSMP) 
10.1 
Internal Audit and Data Safety Monitoring: 
Refer to the Study Monitoring Plan, which is a separate document, for the Data Safety 
Monitoring Plan. This observational cohort study does not meet the definition of a clinical 
trial, and an external DSMC is not required from a design standpoint. Further, the radioligand 
is delivered in tracer quantities and has no pharmacological effect. 
The Study Monitoring Plan describes the strategy, responsibilities, and quality management 
activities in place to ensure adequate protection of the rights, welfare, and safety of human 
subjects and the quality and integrity of the resulting data, in compliance with applicable laws, 
regulations, policies, and guidance. 
 
11 
DATA MANAGEMENT TOOLS 
11.1 
CoRRIE – CRM database 
Directly identifiable information and indirectly identifiable (identified by study ID number) 
information will be stored in CoRRIE. 
 
CoRRIE is a contact database that is used by all ADRC-linked studies. It is a web-based, 
electronic database for contact management that is password-protected and managed by 
DOM. 
In addition to storing the names of those who enroll in this study, the CoRRIE database will 
also help the staff to manage their contacts with participants. The database allows for the 
storage of participants’ relationship to our program by stating which studies in our program 
they are enrolled in or have been enrolled in the past. This allows staff to answer the phone 
call of someone with a memory disorder and be able to tell them when their next visit is and 
who they will be seeing. The database also allows us to track and assign activities that take 
place during the course of research (phone calls, letters, screenings). This helps to ensure that 
participants are not needlessly contacted and overall improves the customer service provided 
to our participants by the members of our research program. The purpose of storing this data 
is for programmatic cohesion in working with subjects with memory problems. It is important 
to know which subjects are enrolled in which studies so that we may provide appropriate 
coordination of their study visits. 
 
UNIVERSAL IDENTIFIER 
An internal ID number is generated by the ADRC CoRRIE database and will have “RMRaic00” 
added to it to create a unique participant identifier that will remain with the participant from 
study to study. This number will be used to label brain images collected in affiliated ADRC 
protocols. This will allow physicians who are reviewing the brain scans to look for brain 
changes over time. 


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11.2 
PANDA and PACS 
Image data management tool: Image data are electronically transferred and stored on servers 
at the ADRC imaging core, and metadata is inserted into an imaging database called PANDA. 
Image headers by protocol do not contain identifying information. Additionally, each image is 
automatically inspected, and any PHI is removed. These resources are maintained by the 
Department of Medicine. Some derived numeric image data and cognitive and questionnaire 
data may be maintained in PANDA. User access is protocol specific such that only users 
authorized to see this study’s data will have access. 
 
MRI and PET images labeled with only study IDs as identifiers may also be uploaded to the 
Dept of Radiology PACS directly from the scanner for radiology over-reads. 
 
11.3 
BOOKED 
Directly identifiable information and indirectly identifiable (identified by study ID number) 
information will be stored in Booked. A participant scheduling web application, Booked, has 
been developed by extending the Booked (PHP) free, open source project. The Booked 
application can prevent double booking of staff and resources, provide email notification to 
staff when they are added to appointments, provide email notification if an appointment has 
been cancelled, and provide email reminders before an appointment starts. Staff can be 
linked to multiple roles in appointments. The calendar view can be filtered by resource, staff, 
and study participant. The appointments are color coded by appointment type and staff 
member. Booked reports can track cancelled appointments, cancellation reasons, 
appointment types, resource usage, staff hour totals, and staff appointment counts. Booked is 
limited to https ssl connections. Only users granted protocol specific permissions can log into 
Booked and view study participant information. It is also important to note that the Booked 
software is installed on the DOM production server in the DOM server room; therefore, all 
Booked data will be on the DOM server. Access to Booked via the web is limited to UW 
Networks. Booked is a free, open source project; therefore, there are no connections or 
relationships with the Booked software manufacturer. Participant Name, phone number and 
ADRC Registry ID (2016-0735) are identifiers used in Booked. Booked is an appointment 
scheduling application, so the participant’s name, phone, and Study ID are needed to identify 
the participant. These identifiers will only be visible to users who are on the protocols that the 
participant is enrolled in. 
12 
PRIVACY 
12.1 
Privacy and Data Storage 
Physical data will be kept in locked cabinets in our lab which has space at the UW Hospital. 
Other data will be kept on the Department of Medicine's secure server and at the Waisman 
Center server which comports with HIPAA security requirements. Only individuals in our labs 
will have access to these computers and any PHI. Any data shared with individuals outside of 
our lab (i.e., papers or presentations) will be coded or anonymized. Each subject will also have 
an individual study number to code their study data. Names are never entered at the scanner 
console, only study numbers. Study numbers are used on data collection forms. 


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2018-1283, NCT04871074   
 
Directly identifiable information and indirectly identifiable (identified by study ID number) 
information will be stored on CoRRIE and Booked. 
 
12.2 
CoRRIE 
CoRRIE refers to the ADRC Registry Protocol (2016-0735); however, it is also an electronic 
database/contact management system that stores information (inclusive of PHI) from the 
'First Contact Form' as described in 2016-0735 and tracks study participation. The electronic 
database is web-based, though only accessible within the DOM server, and is password- 
protected. Data are not stored in temporary files. Registered accounts must be approved by 
our research staff supervisors, and access/activity in the database will be monitored. Only 
those listed on the 2016-0735 protocol will be allowed access. 
12.3 
Booked 
Booked is a participant visit scheduling web application that has been developed by extending 
the Booked (PHP) free, open source project. Booked software has been installed on the DOM 
production server in the DOM server room. All Booked data will be on the DOM server. Access 
to Booked via the web is limited to UW DOM Networks. Booked is a free, open source project; 
therefore, there are no connections or relationships with the Booked software manufacturer, 
and data will not be stored online with the software manufacturer. Booked is limited to https 
ssl connections. Only users granted protocol specific permissions can log into Booked and 
view study participant information. Booked is an appointment scheduling application, so the 
participant’s name, phone number, and Registry ID are needed to identify the participant. 
These identifiers will only be visible to users who are on the protocols which the participant is 
enrolled in. The DOM IT department has been consulted with regard to HIPAA security 
requirements. 
12.4 
PANDA 
PANDA (PAN = Greek prefix meaning ‘all’; Data Archive) is a data and imaging management 
tool that has received IRB approval for use in other ADRC and WRAP linked protocols. Data 
and images are electronically transferred to PANDA, which is maintained by the ADRC imaging 
core. PANDA is a Ruby on Rails application using a MySQL backend database, which provides 
secure web interfaces to a repository of MRI, PET and project-specific variables including 
neuropsychology, lab results, questionnaires, and participant properties. Security of the 
database uses best practice guidelines. Viewing and editing data are separately granted 
permissions and are access-controlled at the project level. Editing of data will be locked to all 
but the DBA. In all cases, this also requires a user to be listed on the IRB-approved protocol 
(via ARROW study team list). For security, all login and query downloads are logged and 
traceable by user and date. Further, any logged query, including table fields and selection 
criteria, may be reconstructed at a later date for auditing if needed. The DBA has an interface 
to view the queries by user/time. As imaging data cannot be uploaded, it is the image 
metadata that are uploaded into the SQL database; the images themselves are stored on a 
secure DOM server in the imaging core as well as in Waisman Center brain imaging lab. Data 


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2018-1283, NCT04871074   
 
are transferred to database users using https downloads of queries in CSV text files that can 
subsequently be imported into statistical analysis software. 
12.5 
REDCap 
REDCap is an electronic data management system that will be used to capture, edit, manage, 
and export study data (inclusive of PHI) for analysis. REDCap is a mature, secure web 
application that can be used to collect virtually any type of data; it is specifically geared to 
support data capture for research studies. The REDCap Consortium is composed of 2,514 
active institutional partners in 116 countries who utilize and support REDCap in various ways. 
All communication between the clients and the REDCap application takes place via Hypertext 
Transfer Protocol over Secure Socket Layer or HTTPS. HTTPS provide the ability for normal 
web-based communication over an encrypted Secure Socket Layer (SSL) connection. This 
ensures that data passing between the client and REDCap is protected. 
The REDCap server is housed in a state-of-the-art data center managed by the UW SMPH 
network staff. The levels of security for the server are fivefold and include: 
1. Physical Security 
The server is located in a secure data center under control of UW School of 
Medicine and Public Health (SMPH) ITS. The server is in a dedicated computer 
machine room (passkey access only) containing emergency backup power, an 
uninterruptible power supply (UPS), and an automatic fire detection and 
suppression system. SMPH ITS does not have access to the DOM REDCap server. 
2. Access controls 
Data access is limited to DOM Faculty and staff-approved individuals. 
3. Domain access restrictions 
Access to DOM computing resources, including the DOM REDCap Server, is 
restricted to individuals with a login ID for the DOM Domain. Login IDs are issued 
only upon approval of the Administrator or Principal Investigator (Data Custodian). 
Login IDs are only issued upon confirmation that the individual has completed 
appropriate training. 
 
4. Authentication 
Password protection is used at the network level for all transactions that allow 
entry and editing of data, provide access to EPHI data, or administrative activities. 
5. Firewall 
The DOM REDCap server is located behind the UW-Madison SMPH firewall. The 
SMPH firewall does not allow outside access to the server itself. Outside access to 
the application is allowed through a combination of firewall rules, reverse proxy 
access, and directory level user authentication. 


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2018-1283, NCT04871074   
 
The REDCap database is backed up hourly, daily, weekly, and monthly. These backups are 
stored in an offsite datacenter. The files on the REDCap server are backed up daily and stored 
in an offsite datacenter. 
 
Within the REDCap software itself, there is an audit trail that includes all operations 
performed on the data. Viewing data or exporting data will trigger a record in the audit log. 
Each audit record includes the operation, date, time, and the user who performed the 
operation. 
At the server level, logs are compiled to track users who login to the server. The server is only 
accessed directly by administrators for administrative or maintenance purposes. Any failed 
login attempts are tracked in order to log potentially malicious activity. 
 
12.6 
FreezerPro 
FreezerPro is a sample management system created by Brooks Automation, Inc. that will link 
each participant’s study visits and their associated biological sample collection kits. The 
application and data will be hosted on the DOM server. Access to the web application is 
managed through DOM LDAP authentication and FreezerPro’s role-based authorization. 
Access to the system is encrypted via HTTPS/TLS secure handshake certificate, and it is not 
accessible from outside the DOM network. Registered accounts must be approved by our 
research staff supervisors, and access/activity in the database will be monitored by system- 
specific supervisors. Additionally, the database will be accessible to a limited number of users 
(coordinator, PI, and other laboratory personnel) with password protection. 
 
13 
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expression of synaptic proteins occurs early during progression of Alzheimer's disease. 
Neurology. 2001; 56: 127-129. 
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Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. 
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A 
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Christian BT, Vandehey NT, Floberg JM, Mistretta CA. Dynamic PET denoising with HYPR 
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Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, Meltzer CC, Schimmel K, Tsopelas 
ND, DeKosky ST, Price JC. Simplified quantification of Pittsburgh Compound B amyloid imaging 
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Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios 
without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996; 
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26. 
Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang 
SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, 
Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, 
Suhara T, Votaw JR, Wong DF, Carson RE. Consensus nomenclature for in vivo imaging of 
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Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K. Staging of Alzheimer disease- 
associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta 
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Alzheimer's disease. Brain. 2015; 138: 2814-2833. 10.1093/brain/awv236 
29. 
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in 
Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011; 70: 
960-969. 10.1097/NEN.0b013e318232a379 
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MedCalc [computer program]. Version 18.2.1. Ostend, Belgium: MedCalc Software; 2018. 
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Colliot O, Chételat G, Chupin M, Desgranges B, Magnin B, Benali H, Dubois B, Garnero L, 
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10.1002/ana.410270502 

ICF_001.pdf: 
Study #: 2018-1283
V7 28FEB2023
Page 1 of 19
     University of Wisconsin-Madison
Consent to Participate in Research
and
Authorization to Use and/or Disclose 
Protected Health Information for Research
Study Title:
The Synapse Project
Study Sponsor:
National Institutes of Health
Principal Investigators:
Barbara Bendlin, PhD
Bradley Christian, PhD
Sterling Johnson, PhD
Contact Information:
CSC J5/1Mezz
600 Highland Avenue
Madison, WI 53792
Phone: (608) 265-2483
Email: bbb@medicine.wisc.edu
Participant Consent
____________________________________
  SYN__________________________
Participant name
  Study ID
Invitation
We invite you to take part in a research study about neuronal synapse abundance as 
shown by PET imaging. We are inviting you to participate in this study because you 
participate in the Alzheimer’s Disease Research Center (ADRC) Clinical Core, the 
Wisconsin Registry for Alzheimer’s Prevention (WRAP) study, or an ADRC-linked study. 
This study enrolls people with healthy memory function, and those with memory disorders 
such as mild cognitive impairment or Alzheimer’s disease.  
The purpose of this consent and authorization form is to give you the information you 
need to decide whether to be in the study. It also explains how health information will be 
used for this study. Data we collect from you will be banked and shared with others for 
future research and we request your authorization (permission) to use your health 
information.  Ask questions about anything in this form that is not clear. If you want to talk 
to your family and friends before making your decision, you can. Once we have answered 
all your questions, you can decide if you want to be in the study. This process is called 
“informed consent.”  
IRB Approval Date: 3/28/2023              
University of Wisconsin – Madison


Study #: 2018-1283
V7 28FEB2023
Page 2 of 19
Why are researchers doing this study? 
The purpose of this research study is to collect brain 
scans that will provide images of “synapses” and to 
determine how synapse health is related to 
Alzheimer’s disease progression and pathology.  
The synapse is located at the end of a neuron (brain 
cell) and is the point at which an electrical or 
chemical signal passes between neurons (see 
photo on the right). Synapses are important for 
neuronal “communication”. As part of this study, 
researchers will evaluate whether the amount of 
synapses that can be measured in the brain are 
related to a person’s cognitive function. The ability 
to image synapses may allow researchers to better 
understand why some people develop Alzheimer’s 
disease dementia. This study will also examine how 
synapse health is related to amyloid and tau 
pathologies (features of Alzheimer’s disease). We 
are doing this research because we have the 
capability to see the pathology that occurs in 
Alzheimer’s disease, and we want to study 
synapses in various stages of the disease.
This study is being done at the University of Wisconsin-Madison (UW-Madison). A total 
of, about, 120 people will be asked to participate in this study between ADRC, WRAP, 
ADCP, and clinics. Funding for this study is provided by the National Institutes of Health.
What will happen in this study? 
PET SCANS: If you decide to participate in this research study, you will participate in 3-
4 Positron Emission Tomography (PET) scans, totaling about 6-8 hours. Approximately 
two years later, we may invite you to undergo the same scans again under this protocol 
or a different protocol as funding allows. Two different scanners are used in this study: a 
PET scanner and a PET/CT (Positron Emission Tomography/Computerized Axial 
Tomography) scanner. Before participating in the scans, people who can become 
pregnant will have a pregnancy test. Additionally, your blood pressure will be taken before 
and after each PET scan you complete, and your blood sugar will be tested (via finger 
puncture) before an FDG PET scan. PET (and PET/CT) scans use very small amounts 
of radioactive compounds that allow researchers to image processes in the brain such as 
synaptic density, amyloid plaques, and tangles. The scans will be performed at the 
Waisman Center or the Wisconsin Institutes for Medical Research (WIMR). Three scans 
will be performed: [C-11]UCB-J to detect synapse density, [F-18]MK6240 to detect 
tangles, and [C-11]PIB to detect amyloid. A possible fourth scan will be performed with 
[F-18]FDG to detect brain activity. For each scan, an IV (needle) will be placed in a vein 
in your arm or hand in order to inject the compounds. Before the main scan begins, a 
Close-up view of synapses. From: 
http://www.nia.nih.gov/alzheimers/p
ublication/alzheimers-disease-
unraveling-mystery/preface
IRB Approval Date: 3/28/2023              
University of Wisconsin – Madison


Study #: 2018-1283
V7 28FEB2023
Page 3 of 19
short transmission scan will occur. If you are scanned on the PET/CT scanner, this 
transmission scan is a CT scan. This transmission scan may need to be repeated. The 
scan will slightly increase your exposure to radiation. After the UCB-J, MK6240, PIB, or 
FDG is injected through the IV, you will be scanned for up to 120 minutes. In some cases, 
the scan duration can be shortened, or may include an “uptake” period where you will sit 
quietly while the compound is absorbed into your body. When you are being scanned, 
you should relax and keep as still as possible. 
UCB-J, PIB or MK6240 have not been approved by the FDA and are considered 
investigational new drugs. We have obtained permission from the FDA to conduct 
research with these compounds. UCB-J is a newly developed compound that binds to (or 
temporarily sticks to) synaptic vesicle glycoprotein 2A (SV2A) which is expressed in 
synaptic vesicles throughout the brain. This reveals information about synaptic density. 
The National Institute on Aging has called SV2A PET imaging a “potentially game-
changing biomarker in AD and AD-related dementias”.
Most participants enrolling in this PET imaging study will also be enrolled in other PET 
imaging sub-studies in our Alzheimer’s disease program. If you have recently participated 
in other PET imaging sub-studies in our program that collect amyloid and tau scans, then 
you will be asked to participate in only the UCB-J scan of the four Positron Emission 
Tomography (PET) scans.  
If completing all four PET (or PET/CT) scans, multiple day visits will occur (but will not 
exceed 4 days). The overall time to complete three PET scans at baseline and potentially 
2 years later will not exceed eight hours total (six if only three scans are being done).   
If any tracer synthesis failure occurs, we will reschedule the visit to a later date.
After the PET (or PET/CT) scans, please 
drink extra fluids and empty your bladder to 
help clear the compounds from your system. 
The compound will clear your system within 
a few hours after the injection.
Participants who have not undergone an 
MRI within the last 12 months in our 
Alzheimer’s disease program will be invited 
to have an MRI. This MRI scan should last 
approximately 60 to 90 minutes and may be 
added to the schedule on days that PET 
imaging occurs.
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MRI SCAN: The MRI scanner will be used to collect detailed pictures of your brain while 
you are lying still on the scanner table. You are asked not to eat for at least 4 hours prior 
to this procedure. Two monitors may be comfortably secured to you to measure your 
pulse and respiration rates during the scan. During the scans it is essential for you to 
remain as still as possible so as not to blur the images. Your head may be held in place 
by foam padding to help you keep still during the scan. The procedure takes up to 120 
minutes. We will situate you as comfortably as possible and then run several scans that 
take 2-15 minutes each. In between scans, you will be able to communicate to the scan 
operator through an intercom. The MRI will be performed at the Waisman Center, WIMR, 
or the University of Wisconsin Hospital and Clinics (UWHC) at the University of 
Wisconsin. Some of the MRI data will be acquired using investigational software and 
hardware installed in addition to the standard software and hardware. The investigational 
software and hardware enable newly developed features that are not yet FDA approved 
for clinical use. Before your scan you will be asked a series of medical history questions 
to make sure it is safe for you to go into the scanner. 
BLOOD DRAW: A blood draw will be done to conduct genetic testing for the APOE4 gene 
(if you have not already done this) as well as to collect plasma and serum for storage and 
test for fasting glucose & insulin. The blood draw will require a minimum 8-hour fast. The 
purpose for an APOE genetic test is to potentially help researchers gain 
information about the genetics of Alzheimer’s disease and if genetics may affect 
the brain activation. Because the clinical utility of the APOE test is not established and 
because it will not be used as part of your clinical care, you will not be told the results of 
the test. The result of the test is not useful in treatment. The result will not go into your 
medical record and will remain confidential. If you have already had APOE testing as part 
of your participation in related studies in our research program, the test will not be 
repeated. If you have your blood drawn on the same day as a study visit for another study 
in the Wisconsin Alzheimer’s Program, we could draw a total of up to 140 mL (about 9.5 
tablespoons).
NEUROPSYCHOLOGICAL TESTING and QUESTIONNAIRES (if not previously done 
with ADRC or WRAP): You will have up to 2 hours of memory and thinking tests and 
questionnaires. These tests will evaluate your memory and other thinking abilities. We 
may ask you questions about your age, health history, medications, family history, 
lifestyle, activities, daily function, mood, quality of life, years of schooling and where you 
live. These will include psychiatric questions about your mental health. Some of the 
questions included in the questionnaires can be embarrassing or stigmatizing. These 
tests may be audio-recorded to make sure we accurately document your responses. You 
may become bored, tired, or frustrated with the difficulty of certain tasks. We will offer 
breaks to you as needed.  
Consensus Diagnosis (if not previously done with ADRC or WRAP): After each 
study visit, our expert clinician and research staff will meet to review the information we 
collect about you and give their opinion about your diagnostic status. In this meeting, we 
review all data from all participants including those with Alzheimer’s disease, mild 
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cognitive impairment, and healthy older controls. We review your diagnostic status after 
every study visit because your cognitive function might change as you continue to see 
our research team year after year. We will protect your identity by not using your name 
or other identifying information during this meeting. You will be contacted if there are 
unexpected findings of clinical concern.
(Optional) LUMBAR PUNCTURE: A lumbar puncture is a procedure in which a needle 
is used to remove spinal fluid from the lower back. An experienced clinician will perform 
the lumbar puncture if you are eligible and meet all the necessary requirements. You will 
be screened prior to scheduling and again on the day of the procedure. For this fasting 
(4 hour fast) lumbar puncture, you will be asked to lie on your side with your knees drawn 
as close to the chest as possible or to sit with your arms and head resting on a table.  
Your lower back will then be numbed with a drug called Lidocaine. Lidocaine will help 
reduce any pain that may be caused by this procedure. A thin needle (typically 1/48 of an 
inch wide, and 3.5 to 4 inches long) will be placed into the space that contains the spinal 
fluid, which is below where the spinal cord ends. One and a half tablespoons of spinal 
fluid will be removed, and the needle withdrawn. If you have your lumbar puncture for this 
study done at the same time as a lumbar puncture for another study, then we might draw 
up to 25 ml (about 5 teaspoons of fluid) from your back. During any lumbar puncture 
procedures, if no spinal fluid is obtained on the first attempt, a second attempt will be 
made after numbing the area with Lidocaine. If the sample of spinal fluid is not drawn 
correctly, you will not undergo another lumbar puncture. The lumbar puncture procedure 
will take approximately 30 minutes. After the lumbar puncture is completed, you will lay 
on your back for about 20 minutes. 
(Optional) ORBITAL X-RAY: If you have a history of metal in your eye(s) as a result of 
past injuries, hobbies, employment, or other life experiences, an x-ray of your eye(s) may 
be done as a safety precaution. This x-ray is optional. However, if you have a history of 
metal in your eye(s) and choose not to participate in the x-ray, you will not be able to 
undergo an MRI. 
Procedures for all 
participants
Additional procedures, if not recently completed via 
another study in our program
<0000>
Vital signs 
(blood pressure, 
pulse, weight)
 
UCB-J scan
 
Blood draw
 
MK6240 scan 
 
PiB scan
 
MRI scan
 
Medical History
 
Physical/Neurological 
Exam
 
Neuropsychological testing
 
CDR interviews
 
Questionnaires
 
(Optional) Lumbar puncture 
 
(Optional) FDG scan
Completion of study procedures will take 1-4 days depending on procedures due and 
the schedules of participants, staff, and facilities. If you are enrolled in a partnering 
ADRC, WRAP, or ADRC-affiliated study, some of your study visits may take place at the 
same time.
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Data use and banking
If you are a participant in either the ADRC, WRAP, ADCP, or another ADRC-linked study, 
researchers will access your ongoing research records from those linked studies to 
determine if you are eligible for PET scans and to determine how results from these PET 
scans relate to  diagnosis, other medical conditions that can affect memory and thinking, 
cognitive testing results, other brain imaging such as MRI and PET scans, results from 
cerebrospinal fluid tests, questionnaires such as sleep and lifestyle surveys, family history 
of Alzheimer’s disease, and APOE genetic test results.
Brain images from this study will be stored for future use so that they can continue to be 
used to better understand memory disorders and dementia. Data banking is explained in 
more detail later in this form.
How long will I be in this study?
You will be a part of the study for approximately 2 years. You will complete the PET (or 
PET/CT) scans (one UCB-J scan, one PiB scan, and one MK6240 scan), an MRI (if one 
from the past 12 months is not available), and a blood draw at a baseline visit and may 
be asked to come back in approximately 2 years to complete the procedures again. An 
optional lumbar puncture and FDG PET scan may occur at both time points as well. 
The researchers may take you out of the study at any point, even if you want to continue, 
if
●
your health changes, and the study is no longer in your best interest
●
you no longer meet the requirements to be in the study
Do I have to be in the study?  What if I say “yes” now and change my 
mind later?
No, you do not have to be in this study. Taking part in research is voluntary. This means 
that you decide if you want to be in the study. If you decide not to take part in the study, 
or if you choose to leave the study, your choice will not affect any treatment relationship 
you have with healthcare providers at UW-Madison, UW Health or any affiliated 
organizations, or any services you receive from them. No matter what decision you make, 
and even if your decision changes, there will be no penalty to you. You will not lose 
medical care or any legal rights.
How we will use your protected health information (PHI) 
Protected health information, also called PHI, is information about your physical or mental 
health that includes your name or other information that can identify you, like your date of 
birth or medical record number. To do this study, we will use the following kinds of PHI:
 
Results of procedures done as part of this study
 
Data described in the “What will happen in this study?” section above that is 
collected at prior and future study visits as part of your participation in the ADRC 
Clinical Core study or WRAP study
 
Things you tell the researchers about your health
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How long will my permission to use my health information last?
Your authorization for researchers to use your protected health information (PHI) does 
not have an end date. However:
●
You can choose to take back your authorization for researchers to use your 
health information. You can do this at any time before or during your participation 
in the research. 
●
If you take back your authorization, information that was already collected may 
still be used and shared with others, but the researchers will no longer be able 
to collect NEW information about you.  
●
If you take back your authorization, you will not be able to take part in the 
research study.
●
To take back your authorization, you will need to tell the researchers by writing 
to the Lead Researcher, Barbara Bendlin (see contact information on page 1). 
Will being in this study help me in any way?
Being in this study will not help you directly. Your participation in the study may benefit 
other people in the future by helping us learn more about Alzheimer’s disease.  
What are the risks? 
Risks of PET imaging: The types of PET (or PET/CT) scans you will have are a [C-
11]UCB-J brain scan (synapse density), [C-11]PIB scan (amyloid scan), an [F-18]MK6240 
scan (tau  scan), and an optional [F-18]FDG scan (brain activity). PET compounds use 
small amounts of radiation to generate images of your brain. This radiation exposure is 
not necessary for your medical care and is for research purposes only. The total amount 
of radiation exposure you could receive from this study is about 12 years’ worth of 
background radiation from natural environmental sources. This amount will not be given 
all at once, but instead spread throughout the course of the study. This amount is well 
below the annual limit set by the federal government for research subjects and, to 
minimize risks, this study uses the lowest possible dose of radioactivity needed to obtain 
a clear image.  
PIB and UCB-J have been used in people extensively worldwide in research with no 
adverse results reported.  
MK6240 is a newer compound but is now being investigated at several institutions 
worldwide (including the UW) with no related serious adverse results reported in over 
6000 scans. In 6378 MK6240 scans completed worldwide, the most commonly occurring 
adverse events possibly related to injection of MK6240 include headache (occurred in 10 
out of 6378 participants, or 0.16%) and dizziness (occurred in 2 out of 6378 participants, 
or 0.03%). The following occurred in only one participant out of 6378, or 0.02%: abdominal 
distention (bloating or swelling in the belly area), injection site bruising, arthralgia (joint 
pain), dysgeusia (altered sense of taste), parosmia (altered sense of smell), insomnia 
(difficulty falling asleep), and dysuria (discomfort when urinating). All reported adverse 
events were considered mild in intensity, and resolved shortly after the scan. There is a 
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risk of mild to moderate pain (e.g. a burning or stinging sensation) with the injection of the 
compound, which typically goes away after a few seconds.
FDG is considered safe and there has not been a report of an adverse event with its use.
Despite this information, there is a risk of having an allergic reaction to the FDG. However, 
this is very rare. Each compound undergoes rigorous safety testing before injection. 
There are no known side effects besides radiation, and the compounds will clear the body 
within a few hours. If you believe you are experiencing adverse symptoms as a result of 
the PET scans, please let the researchers know. 
In general, for PET scans, there is a slight risk of discomfort, bruising, fainting, or infection 
with the placement or removal of the IV needle used for injection. There are no other 
known side effects, and the compounds will clear the body within a few hours. If you 
believe you are experiencing adverse symptoms as a result of the PET (or PET/CT) 
scans, please let the researchers know. 
Reproductive risks: The radiation in this study may be harmful to a fetus or 
breastfeeding baby. For this reason, if you are pregnant or breastfeeding, you cannot take 
part in this study. If you can become pregnant, you must have a negative urine pregnancy 
test on the day of the PET scans. This test will be performed at no cost to you.
Risks of MRI: Some people should not participate in MRI studies. These include persons 
with shrapnel or certain metallic implants, such as prostheses, or aneurysm clips, or persons 
with electronic implants, such as cardiac pacemakers or implanted hearing devices. The 
magnetic field generated by the MR machine can cause a displacement or malfunctioning 
of these devices. There are no other known risks to body tissues associated with the 
magnetic field strength used in this study. Some people report anxiety or claustrophobia in 
the MR scanner since the head must be placed fully inside the scanner tube. If anxiety or 
claustrophobia occurs, please let us know and we will stop the scan right away. Fatigue and 
physical discomfort are also possible. The MRI scanner makes a great deal of noise when 
taking images. You will be fitted with disposable earplugs to reduce the noise volume. 
These will not eliminate all sound, so that communication with you is still possible.
X-ray exam: If you might have any metal in your body as a result of past injuries, hobbies, 
employment, or other life experiences, an x-ray of the affected part of your body may be 
done as a safety precaution before your MRI.
Fasting before MRI, PET, blood draw, or LP: You may be asked to fast before your 
MRI, LP, and blood draw. Fasting means that you cannot eat or drink anything except 
water for 4 hours before an MRI, PET, or LP, and for 8 hours before a blood draw. If you 
are a smoker, nicotine should be avoided for 1 – 2 hours prior to your MRI scan.
 
You may take your usual medications with water only during the fast.  
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Risks of the (optional) Lumbar Puncture (LP): Approximately 22-25 milliliters of spinal 
fluid may be taken during each LP and your body will make up for the loss. During the 
procedure, you may have temporary pain and discomfort in your back. The most common 
complication of spinal fluid collection is a headache. When done in most clinical settings, 
headache occurs in about 10 out of every 100 people who have the procedure. On the 
other hand, the number of people who get headaches is less than 2 out of every 100 
people when a special needle is used. This special needle is used for spinal fluid 
collection in every lumbar puncture in this study. Drinking a lot of fluids before the spinal 
fluid collection may also help prevent headaches, and drinks with caffeine may help treat 
headaches from spinal fluid collections. We will call you the day after your spinal fluid 
collection to see if you have any side effects. During the spinal fluid collection, about 13 
out of every 100 people feel brief electric shocks if the needle touches a nerve. Damage 
to the nerves that come off the spinal cord can rarely occur. In 1 out of every 150,000 
people, bleeding from a broken blood vessel can cause a pocket of blood. If the procedure 
is performed at the improper level, the needle may injure the spinal cord. A doctor does 
a physical exam before the spinal fluid collection to make sure you have no neurological 
conditions that would make spinal fluid collection unsafe. 
Lidocaine: Lidocaine is the drug used to numb the lower back before the collection of 
spinal fluid. There are rare cases of allergic reactions to lidocaine, such as redness and 
swelling of the skin. If you have had a previous reaction to lidocaine, please inform study 
personnel right away.
Risks of Blood Pressure Check: The risk of the blood pressure test is minimal. You 
may experience a few seconds of discomfort as your arm is squeezed by the blood 
pressure device.
  
Risks of blood draw and blood sugar finger test: There may be some discomfort, 
minor bruising, or fainting associated with having blood sampled by venipuncture. There 
is also a very small chance of infection (less than 1%) at the needle puncture site.
Risks of genetic tests: If you take part in the genetic test, the results may create risks for 
you. These risks may include emotional upset, insurance or job discrimination, and/or 
family conflicts from learning unknown information about your parents or blood relatives. 
To protect you from this, results will be deemed for research only and will not be entered 
into the medical record or given to you or family members.
In some cases, a new federal law call the Genetic Information Nondiscrimination Act 
(GINA) makes it illegal for health insurers and employers to discriminate against you 
based on your genetic information. But you should know that there are limitations to this 
law; for example, it does not apply to businesses that employ fewer than 15 people or life 
insurance, disability insurance or long-term care insurance. An abnormal genetic test 
could result in denial or much higher rates for life insurance, disability insurance, or long 
term care insurance if your genetic test results were to become known.
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Risks of neuropsychological testing: These tests may be recorded to make sure we 
accurately document your responses. Recordings will be kept until your tests are scored 
and will be destroyed following scoring. You may become bored, tired, or frustrated with 
the difficulty of certain tasks. We will offer breaks to you as needed.  
Risks of the (optional) Orbital X-ray: Orbital x-rays involve exposure to radiation, 
equivalent to 12 days of background radiation (living on Earth for 12 days). 
Risk of Breach of Confidentiality: Because your personal information will be retained, 
there is a small possibility that your information could become available to unauthorized 
persons. If this happens, it could result in damage to your reputation, which could also 
affect your relationships with family and friends, affect your employment, or make it harder 
to get insurance or a job. As part of this study, researchers are analyzing data collected 
during your WRAP or ADRC participation, which includes sensitive information such as 
memory diagnosis, other medical conditions that can affect memory, cognitive testing 
results, family history of Alzheimer’s disease, and APOE genetic test results. 
Will I be paid or receive anything for being in this study? 
You will be paid as follows:
$100 for a UCB-J scan
$100 for an FDG scan (if being collected as part of this research study)
$100 for a PiB scan (if being collected as part of this research study)
$100 for an MK6240 scan (if being collected as part of this research study)
$75 for an MRI scan (if being collected as part of this research study)
$100 for a lumbar puncture (if being collected as part of this research study)
$25 total for blood draw, physical exam, and cognitive testing (if being collected as 
part of this research study)
You could be paid up to $600 for your baseline participation in this study, and up to $600 
for the potential 2-year follow-up. You will be paid even if you decide to discontinue study 
participation during that visit. Your study partner will be paid $25 for each study visit.
As appreciation for your participation, you may receive a souvenir picture of your brain.  
What happens if I am injured or get sick because of this study?
Being injured during this research is very unlikely. However, accidents can happen. If you 
are injured or get sick because of this study, medical care is available to you through UW 
Health, your local provider, or emergency services, as it is to all sick or injured people. 
 
If it is an emergency, call 911 right away or go to the emergency room. 
 
For non-emergency medical problems contact your regular health care provider.
 
Call the Lead Researcher, Barbara Bendlin, at (608) 265-2483 to report your 
sickness or injury.
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Here are some things you need to know if you get sick or are injured because of this 
research: 
 
If the sickness or injury requires medical care, the costs for the care will be billed 
to you or your insurance, just like any other medical costs. 
 
Your health insurance company may or may not pay for this care.
 
No other compensation (such as lost wages or damages) is usually available.
 
UW-Madison and UW Health do not have a program to pay you if you get sick or 
are injured because of this study.
 
By signing this consent form and taking part in this study, you are not giving up 
any legal rights you may have. You keep your legal rights to seek payment for care 
required because of a sickness or injury resulting from this study. 
How is being in this study different from my regular health care?
The PET and MR scans that you will receive in this study are NOT the same as those 
used to diagnose medical problems. These images, test results and any reports are not 
entered into your medical record. If you are having symptoms that you believe may be 
related to an illness or disease, you should see your primary physician, who will then 
order the types of studies that are required for your medical care.
Possible Discovery of Unanticipated Findings
When brain scans are performed for research, there is a chance of finding something 
unexpected, given your health history. Unexpected findings can be medically important, 
or medically unimportant. Findings that are medically important have clear clinical 
significance and are those for which treatment might be available, and for which we 
generally know the risks of non-treatment.
You will only be informed of findings with clear clinical significance, which may be 
revealed 
during 
the 
MR 
imaging 
procedure 
or 
neuropsychological 
testing/questionnaires. You will not be informed of findings judged as medically 
unimportant by our clinicians.
To assist us in interpreting the results of your tests and brain scans, we are also seeking 
permission to review your medical records if you are or have been a patient at UW 
Hospital and related clinics. Clinical research staff will have access to your entire UW 
Hospital and Clinics Medical Record. 
There may be benefits to learning such results (early detection and treatment of a medical 
condition), but there are risks as well (problems with getting insurance or a job or feeling 
worried about a finding for which no treatment is required or appropriate). Please note 
that any further clinical care or tests you receive from your doctor might lead to costs 
incurred by you or your insurance company. The research team and University of 
Wisconsin will not reimburse you for those additional tests.
You may also choose to have your physician informed of any findings of clear clinical 
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significance that we report to you by checking the box below. Please note, however, 
that if you choose to have your physician informed of findings of clinical significance, 
that report may be placed in your medical records by your physician. We will discuss 
this with you at the time you are informed.
Please indicate your preference by signing your initials on the appropriate line: 
______   Please inform me and my doctor of findings of clinical significance.  
______   Please only inform me. Do not inform my doctor of findings of clinical 
significance.
Name of Physician to contact: 
_________________________________________________
City or Clinic:
_________________________________________________
Additional Contact by Mail, Telephone or Email
Being part of this study means that you will be contacted by study staff before and after 
each visit. We will contact you to make sure that things are going well for you, and that 
we have all the necessary details in place for your next visit.
Sometimes study participants prefer to be contacted via email to arrange scheduling or 
other participation-related details. If that is preferable to you, we will collect your email 
address. Email is generally not a secure way to communicate about your health as there 
are many ways for unauthorized users to get access to email. Please avoid sending 
sensitive, detailed personal information by email. Email should also not be used to convey 
information of an urgent nature. If you need to talk to someone immediately due to a 
medical emergency, call 911. For non-emergency calls, you may also contact our on-call 
clinician: call 608-263-6400 to reach the UW page operator and provide the name of the 
clinician from your last visit. Clinicians involved on this study include Dr. Nathaniel Chin 
and Dr. Cynthia Carlsson. You do not have to provide your email address to participate 
in this study. If you agree to share your email address, please provide it here:
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Continued Participation
Some persons may progress to the point where they are no longer able to competently 
make their own decisions regarding medical research. If we suspect you have lost this 
capacity, we will evaluate this. You can choose now if you want to continue in this study 
should you lose mental capacity to make this decision later. Please initial one of these 
options:
______   Yes, I wish to continue participating even if my decisional capacity becomes 
impaired.
______   No, If I become impaired, I wish to stop participating in this study.
If you would like to continue your participation in the study, please write the name of the 
surrogate you would like to make decisions on your behalf.
Name of Surrogate
How will the researchers keep my research information confidential? 
We have strict rules to protect your personal information and protected health information 
(PHI). We will limit who has access to your name, address, phone number, and other 
information that can identify you. We will also store this information securely. We may 
publish and present what we learn from this study, but none of this information will identify 
you directly without your permission. 
However, we cannot promise complete confidentiality. Federal or state laws may permit 
or require us to show information to university or government officials responsible for 
monitoring this study.
Others at the UW-Madison and its affiliates, who may need to use your health 
information in the course of this research: 
 
UW-Madison regulatory and research oversight boards and offices
 
Accounting and billing personnel at the UW-Madison
 
Research support services staff at the UW-Madison and its affiliates
Others outside of UW-Madison and its affiliates who may receive your health 
information in the course of this research: 
 
U.S. Office for Human Research Protections
 
The sponsor of the study, National Institute of Health
 
National Alzheimer’s Coordinating Center (via Laboratory of Neuroimaging (LONI))
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Cerveau Technologies, provider of the MK6240 compound
 
Authorized representatives of the U.S. Food and Drug Administration (FDA)
 
Researchers conducting work relevant to dementia or aging who apply to use your 
coded data
 
Other NIH-specified repositories
Will information from this study go in my medical record?
Authorizing the research team to use your PHI means that we can release it only to the 
people or groups listed above, and only for the purposes described in this form. However, 
once your health information is released outside UW-Madison or UW Health it may not 
be protected by privacy laws and might be shared with others.  
Also, if ALL information that can identify you is removed from the health information 
collected in this study, then it is no longer PHI, and this authorization will no longer limit 
how the remaining information can be used. This means the information could be used 
or shared for reasons other than the ones described in this form such as a research study 
about another kind of disease. It also means that the information could be shared with 
researchers working at institutions that are not listed above.
The PET images, MRI images, and spinal fluid samples collected in this study will be 
coded with unique participant numbers. This coding means no one except study 
personnel will know your identity and test results. If you participate in a partnering ADRC 
or WRAP study, researchers from that study will have access to the code and images. 
Any data that leaves the UW will be coded.
Because some of the study procedures you will undergo will be on the Clinical Research 
Unit (CRU) unit, your visit to the CRU will be recorded in an electronic medical record. If 
you receive care through UW Health, this information will be included in your existing 
medical record. If you do not already receive health care through UW Health, a record will 
be created for you.
This means that if you receive health care from UW Health, your UW Health providers will 
see that you took part in a research study. If you are participating in a study as a “normal 
healthy volunteer” (for example if you might be at risk for Alzheimer’s disease but you 
don’t have it), the title and purpose of the research study you are taking part in will not 
appear in the electronic medical record and you will be identified as a healthy volunteer 
to help protect your privacy.
Some of the results of the procedures or tests performed for the study will be recorded in 
your electronic medical record and others will not. Results that would not link you to 
Alzheimer’s disease or results that are not considered sensitive information will be placed 
in your electronic medical record, such as nursing documentation, results of blood work, 
and the results of cell counts performed after the Lumbar Puncture. 
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Study results that would link you to Alzheimer’s disease or are considered sensitive 
information will not be placed in your electronic medical record without your consent. This 
means that if you have UW Health care providers, they may be able to discover the results 
of those study tests that are put in your electronic medical record. Because the 
procedures being done for this study are being done for research purposes only, the study 
team does not plan on reporting the results back to you unless they suggest a clinical 
concern. However, because the results of your tests are resulted in your UW Health 
record, your usual health care providers may follow up with you regarding the tests. If 
your health care providers discover your results and want to perform additional follow up 
tests, that is up to them. If your UW Health care provider asks you why you visited a UW 
Health facility, such as the CRU, and had procedures or tests done, you can simply state 
that you participated in a research study and do not need to share the details of the study.
If you have any questions about what information will go into the electronic medical record 
created for you, ask the study team for more information.
Certificate of Confidentiality
To help us protect your privacy, we have obtained a Certificate of Confidentiality from the 
National Institutes of Health. The researchers can use this Certificate to legally refuse to 
disclose information that may identify you in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings, for example, if there is a court subpoena. 
The researchers will use the Certificate to resist any demands for information that would 
identify you, except as explained below.
The Certificate cannot be used to resist a demand for information from personnel of the 
United States federal or state government agency sponsoring the project and that will be 
used for auditing or program evaluation of agency funded projects or for information that 
must be disclosed to meet the requirements of the Federal Food and Drug Administration 
(FDA). You should understand that a Certificate of Confidentiality does not prevent you 
or a member of your family from voluntarily releasing information about yourself or your 
involvement in this research. If an insurer, medical care provider, or other person obtains 
your written consent to receive research information, then the researchers will not use the 
Certificate to withhold that information.
If you indicate your intent to harm yourself or others, the Certificate of Confidentiality 
cannot be used to prevent disclosure of that intent to state or local authorities. 
Data Banking for Future Unspecified Research 
In the future, there may be additional research studies conducted on the data we collect 
to better understand memory disorders and dementia. By storing your brain images and 
test results for future study, researchers may be able to develop or test future biological 
markers. Your brain images will be stored indefinitely in the UW Hospital, Wisconsin 
Institutes for Medical Research, or VA Hospital in Madison, WI. The data and images may 
be shared with other researchers at the University of Wisconsin-Madison and outside the 
University. If you want to have your data removed from the study, you may contact Dr. 
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Bendlin at the address or phone number listed on page 1 of this form. The brain images 
will be marked with a code and not your identifiable information.
Sharing Results
As a participant of the Alzheimer’s Disease Research Center Clinical Core (ADRC) or the 
Wisconsin Registry for Alzheimer’s Prevention (WRAP), you agree that prior and future 
results from the main ADRC or WRAP study be made available to this linked study so we 
can relate the findings to your ADRC or WRAP tests. These prior results include 
neuropsychological testing (i.e., memory testing), laboratory and genetic tests, surveys, 
medical history (including family history of AD), MRI brain images, PET brain images, and 
cerebrospinal fluid results. By signing this consent, you also give permission for us to 
share the information gathered in this study with the main ADRC or WRAP study, 
depending on which study you are a participant in.
Data sharing
As the sponsor of this study, the NIH requires that we share the data collected from you 
with other researchers to increase the scientific value of the data. The Lead Researcher, 
Dr. Bendlin, will be responsible for deciding how and with whom your data will be shared. 
Information about you will only be shared in a coded manner so that you will not be directly 
identifiable. Data sharing may include sending your coded data to a “bank,” or repository 
of brain images, including ones maintained by the NIH. Those repositories will keep your 
data and may send your coded data to other investigators who apply to use it. Data 
sharing may also include sharing your coded data with private, for-profit institutions or 
companies who apply to use it. 
By signing this consent form, you agree to the sharing of your brain images and data with 
qualified UW and non-UW researchers. Other researchers must apply to use the data 
and may only use it for the approved purposes. 
What if I have questions? 
If you have questions about this research, please contact the Lead Researcher, Barbara 
Bendlin, PhD at (608) 265-2483. If you have any questions about your rights as a research 
subject or have complaints about the research study or study team, call the confidential 
research compliance line at 1-833-652-2506.  Staff will work with you to address concerns 
about research participation and assist in resolving problems.
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Pregnancy Screening
The radiation in PET (and PET/CT) scans may be harmful to a fetus. For these reasons, 
this study is not approved for the enrollment of pregnant women. You should only take 
part in this study only if you are certain you are not pregnant. If applicable, a pregnancy 
test will be conducted prior to each PET visit.
I confirm that I am not pregnant and am not planning on becoming 
pregnant during this study.
Signature of Participant
Date 
N/A (Participant is male)
Souvenir Picture
As appreciation for your participation, you may receive a souvenir picture of your brain. If 
you have questions about your health, contact your primary care provider. You (or your 
insurance company) will be responsible for costs related to any follow-up care. 
______   Yes, I wish to receive a souvenir picture.
______   No, I do not want a souvenir picture.
N/A (MRI is completed under a different protocol.)
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Consent Form Questions
Do you have to participate in this study?
____________________________________________________________________
____________________________________________________________________
What would you do if you decided that you no longer wanted to participate?
____________________________________________________________________
____________________________________________________________________
Do you understand that there is a small risk of harm?
____________________________________________________________________
____________________________________________________________________
Do you want to participate in the procedures that have just been described to 
you?
______________________________________________________________________
____________________________________________________________________
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Agreement to participate in the research study
AND
Permission to use and/or disclose my health information
You do not have to sign this form. If you refuse to sign, however, you cannot take part in 
this research study.
If you sign the line below, it means that:
●
You have read this consent and authorization form.
●
You have had a chance to ask questions about the research study, and the 
researchers have answered your questions.   
●
You want to be in this study.
●
You give authorization for your protected health information to be used and 
shared as described in this form.
 
______________________________________________________________________
Printed Name of Research Participant
_____________________________________________________________________
Signature of Research Participant                       
                                Date                                    
______________________________________________________________________
Signature of Person Obtaining Consent and Authorization                           Date
****************************************************************************************************
Please provide the research team with your study partner’s contact information, so we 
can contact her/him to schedule an interview about you.
Name (study partner)
Phone number
Mailing address
Relationship to Participant
N/A (Participant is a part of the ADRC or WRAP studies.)
**You will receive a copy of this form**
IRB Approval Date: 3/28/2023              
University of Wisconsin – Madison