Neuroimaging in Healthy Aging and Senile Dementia (HASD_IND)

Study Overview
=================
Brief Summary
-----------------
To identify factors that signal the transition from asymptomatic (preclinical) to symptomatic Alzheimer disease (AD).

Detailed Description
-----------------
The purpose of this research study is to evaluate the structure and function of the brain in healthy aging and early Alzheimer's disease using positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT) imaging. The study involves imaging the brain to detect the presence of amyloid deposits (plaques in the brain). Amyloid is a protein that may be related to dementia of Alzheimer's disease (DAT). This study will use radioactive tracers called C-11 Pittsburgh Compound B (PIB) and F 18/ AV-1451 (Flortaucipir) which binds to beta amyloid and tau in the brain. These compounds are considered investigational, which means that they have not been approved by the United States Food and Drug Administration (FDA).

Official Title
-----------------
Neuroimaging in Healthy Aging and Senile Dementia (HASD_IND)

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: [11C]-Pittsburgh Compound B ([11C]PiB)
* Drug: F 18 AV-1451 (Flortaucipir)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, any race Age > 18 years Participation in one of the ongoing projects affiliated with the Knight ADRC at Washington University and referred by the MAP staff and a Washington University physician. Normal cognition or early-stage symptomatic AD Willing and able to undergo study procedures. Capacity to give informed consent and follow study procedures Exclusion Criteria: Has any condition that, in the Investigator's opinion, could increase risk to the participant, limit the participant's ability to tolerate the research procedures, or interfere with the collection/analysis of the data (e.g., participants with severe chronic back pain might not be able to lie still during the scanning procedures); Has hypersensitivity to either AV-1451 or PIB or any of its excipients; Contraindications to PET, CT or MRI (e.g. electronic medical devices, inability to lie still for extended periods) that make it unsafe for the individual to participate; Severe claustrophobia; Currently pregnant or breast-feeding. Women must agree to avoid becoming pregnant and must agree to refrain from sexual activity or to use reliable contraceptive methods for 24 hours following administration of Flortaucipir injection; Must not have participated in any clinical trial involving a study drug or device within the 30-days prior to study enrollment; Must not participate in another drug or device study prior to the end of this study participation; Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| African American<br>African American participants receiving [11C]-Pittsburgh Compound B ([11C]PiB) F 18 AV-1451 (Flortaucipir) for imaging. | Drug: [11C]-Pittsburgh Compound B ([11C]PiB)<br>* A dosage range between 6.0 - 20.0 mCi (222-740 MBq) is planned for [11C] PIB. A PET-certified medical professional will prepare and administer the [11C] PIB tracer. Prior to the administration, the dosage will be assayed in a dose calibrator and diluted with 0.9% sodium chloride (normal saline) up to a total 20 mL syringe volume. Participants will receive a maximum intravenous bolus injection of 20.0 mCi of [11C] PIB followed by a 10 mL 0.9% sodium chloride (normal saline) flush.<br>* Other names: PiB;Drug: F 18 AV-1451 (Flortaucipir)<br>* A dosage range between 6.5 - 10.0 mCi (240-370MBq) is planned for [18F] AV-1451. A PET-certified medical professional will prepare and administer the [18F] AV-1451tracer. Prior to the administration, the dosage will be assayed in a dose calibrator. The volume of 18F-AV-1451 dose should not be adjusted by adding normal saline to the syringe. Participants will receive a maximum intravenous bolus injection of 10.0 mCi of [18F] AV-1451 followed by a 10 mL flush of 0.9% sodium chloride (normal saline).<br>* Other names: F 18 AV-1451;|
| Non-Hispanic White<br>Non-Hispanic White participants receiving [11C]-Pittsburgh Compound B ([11C]PiB) F 18 AV-1451 (Flortaucipir) for imaging. | Drug: [11C]-Pittsburgh Compound B ([11C]PiB)<br>* A dosage range between 6.0 - 20.0 mCi (222-740 MBq) is planned for [11C] PIB. A PET-certified medical professional will prepare and administer the [11C] PIB tracer. Prior to the administration, the dosage will be assayed in a dose calibrator and diluted with 0.9% sodium chloride (normal saline) up to a total 20 mL syringe volume. Participants will receive a maximum intravenous bolus injection of 20.0 mCi of [11C] PIB followed by a 10 mL 0.9% sodium chloride (normal saline) flush.<br>* Other names: PiB;Drug: F 18 AV-1451 (Flortaucipir)<br>* A dosage range between 6.5 - 10.0 mCi (240-370MBq) is planned for [18F] AV-1451. A PET-certified medical professional will prepare and administer the [18F] AV-1451tracer. Prior to the administration, the dosage will be assayed in a dose calibrator. The volume of 18F-AV-1451 dose should not be adjusted by adding normal saline to the syringe. Participants will receive a maximum intravenous bolus injection of 10.0 mCi of [18F] AV-1451 followed by a 10 mL flush of 0.9% sodium chloride (normal saline).<br>* Other names: F 18 AV-1451;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AD Biomarkers seen on Amyloid PET at Baseline and Years 1, 2, and/or 3 | This Project aims to identify factors that signal the transition from asymptomatic (preclinical) to symptomatic Alzheimer disease (AD). This will be done by comparing imaging biomarkers seen with amyloid PET and the tracer C-11 PIB at baseline to imaging biomarkers collected longitudinally, at years 1, 2, and/or 3. | 5 years | 
| AD Biomarkers seen on Tau PET at Baseline and Years 1, 2, and/or 3 | This Project aims to identify factors that signal the transition from asymptomatic (preclinical) to symptomatic Alzheimer disease (AD). This will be done by comparing imaging biomarkers seen with tau PET and the tracer Flortaucipir at baseline to imaging biomarkers collected longitudinally, at years 1, 2, and/or 3. | 5 years | 
| AD Biomarkers seen on MRI at Baseline and Years 1, 2, and/or 3 | This Project aims to identify factors that signal the transition from asymptomatic (preclinical) to symptomatic Alzheimer disease (AD). This will be done by comparing imaging biomarkers seen with MRI at baseline to imaging biomarkers collected longitudinally, at years 1, 2, and/or 3. | 5 years | 
| Compare and Correlate Predictive Ability of Biomarkers Seen with Different Imaging Variables for Onset of Symptoms | This project aims to compare and correlate the predictive ability of baseline values and rates of change of molecular biomarkers of AD for onset of AD symptoms with other variables. Variables obtained in this project include: 1) volumetric MRI, 2) MRI measures of vascular burden, 3) functional MRI, 4) amyloid PET, and 5) tau PET. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare and Correlate Predictive Ability of Biomarkers Seen with Other Types of Variables for Onset of Symptoms | This project aims to compare and correlate the predictive ability of baseline values and rates of change of molecular biomarkers of AD for onset of AD symptoms with other variables obtained through Knight ADRC data sharing, which include, 1) clinical (demographic information, socioeconomic status, Clinical Dementia Rating, etiology of cognitive disorder (when present), and comorbid disorders, including cardiovascular disease); 2) cross-sectional and longitudinal cognitive performance, 3) indicators of sleep disruption 4) APOE genotype and genetic variants associated with resilience novel CSF analytes of neurofilament light chain, neurogranin, and SNAP-25 as markers of axonal and synaptic injury. | 5 years | 
| Disparities for molecular biomarkers of AD in non-Hispanic white (NHW) and African American (AA) older adults | The study will also focus on disparities for molecular biomarkers of AD in non-Hispanic white (NHW) and African American (AA) older adults. Aim 2 will compare the risk (or the hazard) of developing AD symptoms by race, and will treat death as a potential competing risk in the progression of dementia. | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dementia, Neuro-Degenerative Disease, Amyloid Plaque, Mild Cognitive Impairment, Brain Disease