Autopsy Follow-up of Subjects Previously Imaged With Florbetapir F 18 (18F-AV-45) PET in Trial 18F-AV-45-A07

Study Overview
=================
Brief Summary
-----------------
This study is designed to test the relationship between measurements of brain amyloid using florbetapir F 18 PET imaging and true levels of amyloid plaque density as measured by histopathological assessment. The study will address the following specific aims: To expand the number of subjects included in the A07 (NCT00857415) trial correlation analysis (measuring the correlation between the global visual rating of brain amyloid plaque density on an independent blinded read of the florbetapir F 18 PET scan and the cortical amyloid plaque density at autopsy as assessed by histopathology for subjects in the autopsy cohort). To determine the sensitivity and specificity of an independent blinded visual read assessment of the florbetapir F 18 PET scan (Aβ+ or Aβ-) versus the final blinded neuropathological assessment made at autopsy.

Official Title
-----------------
Autopsy Follow-up of Subjects Previously Imaged With Florbetapir F 18 (18F-AV-45) PET in Trial 18F-AV-45-A07

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: florbetapir F 18


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects are enrolled in this study if they: Met entrance criteria and were enrolled and imaged in trial 18F-AV-45-A07 (NCT00857415) Gave informed consent for the 18F-AV-45-A07 (NCT00857415) study procedures and brain donation consistent with the legal requirements of the State in which they are enrolled and the State in which they die Consent to participate in the 18F-AV-45-A16 (NCT01447719) extension protocol, if required by the IRB Reconfirm their consent to a research brain autopsy, if required by the IRB.

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

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

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

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

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: florbetapir F 18|No study drug administered in this trial. Study subjects previously dosed with 18F-AV-45 in study 18F-AV-45-A07 (NCT00857415) are followed to autopsy in this extension study.|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity Analysis in All Autopsy Population | Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD (Consortium to Establish a Registry for AD) criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative). | at autopsy within 24 months of florbetapir PET scan | 
| Specificity Analysis in All Autopsy Population | Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative). | at autopsy within 24 months of florbetapir PET scan | 
| Correlation of Florbetapir-PET Image and Amyloid Plaque Density | Spearman's rank order correlation of the median visual read of the florbetapir-PET image and the amyloid plaque density assessed post-mortem by quantitative immunohistochemistry (IHC) averaged across 6 brain regions (precuneus, parietal cortex, frontal cortex, temporal cortex, posterior cingulate, anterior cingulate). Spearman's rank order correlation ranges from -1 to +1. A value of -1 indicates perfect negative correlation, and a value of +1 indicates a perfect positive correlation. | at autopsy within 24 months of florbetapir PET scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity Analysis in Subjects With Autopsy Within 1 Year of Scan | Sensitivity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative). | at autopsy within 12 months of florbetapir PET scan | 
| Specificity Analysis in Subjects With Autopsy Within 1 Year of Scan | Specificity of florbetapir-PET scan to detect moderate to frequent amyloid plaques. Plaque density was calculated using CERAD criteria. Florbetpir-PET scans were read by five independent readers blinded to clinical information using the binary read method (amyloid positive/negative). | at autopsy within 12 months of florbetapir PET scan |