D_SOW.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Neuroinflammation as a mechanism linking Alzheimer’s Disease (AD) pathology and vascular risk factors to dementia.

Statement of Need and Purpose:

Alzheimer‘s disease (AD) is a devastating and global public health problem, but with no public health interventions. Cardiovascular risk factors (CVRF), particularly those present in middle age, contribute to later-life dementia. CVRF leads to vascular disease, which creates a chronic inflammatory state, and along with B-amyloid plaques and tau neurofibrillary tangles, lead to neuroinflammatory damage in brains, detected until recently only at autopsy. Recent advances in Positron Electronic Topography (PET) enables us to quantify in vivo the neuroinflammatory load in the brains of well-described cohorts thus giving us the opportunity to relate vascular risk factors, including lifestyle and sub-clinical disease, and AD pathology to inflammation in the brain and to poor brain health, measured with brain Magnetic resonance imaging (MRI) and cognitive testing.

Background Information and Objective:

The objective of this requirement is to obtain a measure of astroglyosis, an indicator of cerebral neuroinflammation. Astroglyosis plays a role in initiating or propagating inflammatory and oxidative processes in the brain and can now be measured with PET scans using the ligand 18F-SMBT-1. For this requirement, scans should be acquired on a sample representative of the community that is diverse; and that has been examined for mid- and late-life cardiovascular risk factors, AD pathology and brain health.

The already established HeartScore ( 2003-on-going) cohort meets the needs of this requirement: Cardiovascular risk factors have been measured in a sample of Black and White participants (n=2000) since its inception in 2003 when the mean age was 59-(SD 7.5) years with 74% <65 years old. Participants were recruited based on their mid-life cardiovascular risk factor load (low, middle, high), and PET scans to detect B-amyloid and tau deposition have recently been acquired. In the most recent follow-up of the cohort (mean age 74.1 years), 41 participants had evidence of a high cardiovascular risk factor load and 75 had a low cardiovascular risk factor load; 20% had evidence of AD pathology.

References:

1. Astroglial Markers Poised for Stardom? Alzforum.org March 25, 2021

2. Shane A Liddelow, Kevin A Guttenplan, Laura E Clarke, et. al. Neurotoxic reactive astrocytes are induced by activated microglia Nature. 2017 Jan 26; 541(7638): 481–487.PMCID:

PMC5404890; NIHMSID: NIHMS854157

3. Borroni E, Bohrmann B, Grueninger F, et. al. Sembragiline: A Novel, Selective Monoamine Oxidase Type B Inhibitor for the Treatment of Alzheimer’s Disease. Journal of Pharmacology and Experimental Therapeutics September 2017, 362 (3) 413-423; DOI:

https://doi.org/10.1124/jpet.117.241653.

https://doi.org/10.1124/jpet.117.241653

4. O'Connor AT, Clark MA. Astrocytes and the Renin Angiotensin System: Relevance in Disease Pathogenesis. Neurochem Res. 2018 Jul;43(7):1297-1307. doi: 10.1007/s11064-018- 2557-0. Epub 2018 Jun 1. PMID: 29858771.

Period of Performance:

The period of performance is for two years, with an anticipated start date of September 1, 2021.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work. General requirements include: an already existing diverse cohort characterized by mid and late-life cardiovascular risk factors and AD pathology load; ability to perform PET scans quantifying astroglyosis load; and ability to process and interpret the PET scans.

Specific Requirements:

1. Select and invite participants who have participated in the baseline and at least one follow-up of the HeartScore Study; and have recent measures of cardiovascular risk load, AD pathology, and measures of brain health, including brain MRI and cognitive tests.

2. The sample should include 15 individuals who have a high cardiovascular risk load; and 15 individuals who have a low cardiovascular risk load. If feasible given the sample size include participants that: a. self-report as Black or Non-Hispanic White; b. carry the Apolipoprotein E*4 allele, a marker of genetic susceptibility for AD.

3. Acquire PET scans using the ligand 18F-SMBT-1 on the above described 30 participants,

4. Based on documented image maps and guidelines for interpretation, process and analyze the PET 18F-SMBT images for the location and level of signal indicating SMBT-1 retention (astroglyosis).

5. Provide electronic excel sheets that include the location and amount of retained 18F-SMBT (astroglyosis).

6. Provide documentation on radiation and other safety measures taken to protect the participants and their data.

7. Provide electronic Excel sheets that include the following data on the participants:

demographics, mid and late-life cardiovascular risk factors; B-amyloid and tau pathology; MRI volumes of brain regions of interest, and cognitive test scores to address the question of neuroinflammation as a mechanism linking AD pathology and vascular risk factors to dementia.

8. Every four (4) months provide a progress report to the National Institute on Aging (NIA) Program Officer.

LEVEL OF EFFORT:

The Study Investigator shall direct the study, including organize selection, invitation, screening and preparation of the participant for the scan; acquisition of the scan; analysis, interpretation and reporting of the data; preparation of the dataset for delivery to NIA. The Study coordinator shall interface with all participant related activities, a regulatory coordinator to monitor the regulatory complexity of this study that includes PET tracers (and the attendant levels of complexity) to inform various groups about the use of the ligand and a Data analyst to analyze the PET data and compile the dataset for delivery to NIA. Further, expert oversight in Neurology, Molecular Imaging and Radiology is needed for protocols and interpretation of data.

DELIVERY OR DELIVERABLES

MS Excel files with de-identified IDs of the 30 participants who meet selection criteria [see above]. Specific files should include:

1. PET 18F-SMBT-1 location and retention by brain regions of interest;

2. Other brain data (PET AD pathology load; MRI volumes of whole brain and regions of interest; cognitive tests);

3. Demographic and mid- and late-life cardiovascular risk factor data;

4. Protocols, including quality control measures, and on any measures to be used as a part of this contract;

5. Documents prepared for Regulatory purposes, and

6. Informed consent documentation.

A final data delivery and report shall be delivered electronically within 12 weeks of completing the preparation of the PET data.

REPORTING REQUIREMENTS

See above

OTHER CONSIDERATIONS

Travel:

No travel required.

Key Personnel:

Senior supervisors in Neurology (expertise Dementia and cognitive aging), Psychiatry (Molecular imaging), and Radiology (PET Methods and Data Analysis); Investigator to coordinate the study, Patient coordinator, Regulatory coordinator, and a Data analyst to merge different data streams and prepare excel files for NIA.

Information System Security Plan:

N/A

Data Rights:

The National Institutes on Aging shall have unlimited rights to, and ownership of, all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.”

Section 508—Electronic and Information Technology Standards:

The contractor shall comply with Section 508 of the Rehabilitation Act (29 U.S.C. § 794d), as amended by the Workforce Investment Act of 1998 (P.L. 105-220), August 7, 1998.

Publications and Publicity:

N/A

Confidentiality of Information:

Data will be de-identified. The link between this study ID and personal data will be kept in a locked area assessable only to the PI of HeartScore follow-up study.