Positron Emission Tomography in GESTALT participants

The National Institutes of Health (NIH), National Institute on Aging (NIA) intends to negotiate, under authority of FAR 6.302-1, on a noncompetitive, sole source basis, with Johns Hopkins University, Baltimore, Maryland. This notice of intent is not a request for competitive proposals. A solicitation document will not be issued, and proposals will not be requested. However, responsible sources may express their interest by submitting a capability statement or proposal. All capability statements or proposals received within this notice's response date will be considered by the Government. A determination by the Government not to complete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will normally be considered solely for the purpose of determining whether to conduct a competitive procurement. BACKGROUND: The National Institute on Aging (NIA) initiated amyloid PET imaging with Pittsburgh compound B (PiB) in the Baltimore Longitudinal Study of Aging (BLSA) in 2005 and tau PET imaging with AV-1451 (T-807) in 2016. Consistent with autopsy data from BLSA and other studies, approximately 30% of cognitively normal individuals have detectable amyloid deposition in the brain on PET-PiB imaging. Individuals with higher levels of ?-amyloid are older, more likely to carry the Apolipoprotein E ?4 allele, have greater longitudinal decline in memory and other cognitive functions, and are more likely to accumulate amyloid over time. In addition, through the BLSA autopsy program, we have shown the correspondence between in vivo imaging and post-mortem values of amyloid burden (13,18). Work by our group has been central to defining the relationship between amyloid burden and memory change (17,23), to characterizing the magnitude and spatial pattern of progression of amyloid burden (2,4,7,11,16), to highlighting the importance of individuals with intermediate amyloid levels that would be considered PiB negative in many binary classification schemes (7,16), and to identifying modifiers of amyloid burden (3,7,9,10,12,20,21). The NIA has also developed an approach for estimating age at onset of amyloid accumulation, providing an individualized index that can be used as a dependent outcome to assess factors that may modify age at onset of amyloid accumulation (4). This approach was applied to demonstrate that Apolipoprotein E ?4 genotype is associated with earlier age of onset of amyloid accumulation in the BLSA sample. The BLSA was initiated in 1958 and is a multi-disciplinary study of physiologic and psychologic aspects of normal aging in community-dwelling men and women. Since 1994, the NIA has been conducting a longitudinal brain imaging study of selected older adults in the BLSA to characterize individual differences in longitudinal brain changes, to investigate the extent to which these brain changes underlie individual differences in cognitive aging, to identify brain changes that may be predictors of cognitive decline and Alzheimer's disease (AD), and to assess the impact of potential modulators of brain and cognitive aging. More recently, the NIA has been collecting in vivo measures of brain amyloid and tau, the hallmark pathologies of AD, using PET scanning. The NIA intends to extend PET amyloid and tau studies to GESTALT (N=50 over 5 years) because BLSA and GESTALT include many overlapping assessments and participants are drawn from similar populations. This will allow the NIA to combine and analyze data across the two studies to increase power, while recognizing the relative strengths and weaknesses of each cohort. The increase in sample size will also result in an increased number of amyloid (and tau) positive individuals, who provide critical information on the earliest stages of preclinical AD. With the more recent initiation of the NIA GESTALT study, NIA is extending these studies of cognitive and brain aging to a group of individuals undergoing deep phenotyping with respect to blood cell markers. The purpose of GESTALT is to perform deep phenotyping to identify biomarkers that change with aging in individuals who are initially healthy, independent of changes in specific PBMC cell types. The data collected in PBMCs will be compared to similar biomarker data obtained from muscle/fat and skin biopsies to understand to what extent biomarkers measured in the blood recapitulate similar changes that occur in different human tissues. These analyses will provide new insights into the biological nature of the aging process and how aging is associated with decline of both physical and cognitive function. PURPOSE AND OBJECTIVES: The objective of this requirement is to extend these PET studies to GESTALT participants. A better understanding of "age-related" changes also requires definition of the various neuropathologies that accumulate in conjunction with advancing age. The Government collects detailed neuroimaging, as well as cognitive measures in both BLSA and GESTALT study participants. The Government acquire measures of regional brain volume (MPRAGE) and vascular lesion burden (T2, FLAIR), white matter integrity (DTI), and functional networks (resting state functional MRI). In a limited number of BLSA participants, we also acquire measures of amyloid and tau through PET molecular imaging and will extend these molecular imaging studies to GESTALT participants. In combination, the longitudinal assessment of these different modalities will provide insights into the neurobiological underpinnings of both disease- and age-related cognitive changes. This information will answer the question of whether accumulating neuropathologies fully account for age-related cognitive change or if there is some degree of age-related cognitive decline that is intrinsic to the aging process, i.e. "normal aging". Specifically, the purpose is to acquire services to perform and quantify in vivo brain scans, including amyloid and tau neuropathology and regional cerebral blood flow, using Positron Emission Tomography (PET) in GESTALT for analysis in combination with BLSA PET data. Studies of changes in amyloid deposition will be conducted using PET and 11C- Pittsburgh Compound-B (PiB) and studies of changes in tau pathology will be conducted using PET and 18F-T807 from Avid Pharmaceuticals (Lilly). The following are two goals to satisfy NIA's objective fully: 1. Investigate changes in brain function and amyloid and tau burden as early biomarkers of cognitive decline and impairment including Alzheimer's disease. 2. Identify possible protective factors which prevent or delay the onset of cognitive impairment in individuals who maintain normal cognition despite substantial amyloid and tau burden. PROJECT REQUIREMENTS: The Government will provide structural MRI scans and the Contractor shall perform PET 11C- PiB, and 18F-T807 scans and assist in sophisticated quantitative analysis of imaging data, using kinetic modeling techniques. The Contractor shall provide: - Assistance with scheduling the PET scan studies. - Assistance with preparation and review of regulatory documents, including materials to meet Institutional Review Board, FDA, and radiation safety regulatory requirements. - Radioisotope administration. - Medical monitoring of participants during PET scan procedures. - Provide parking coupon and lunch to research participants when necessary. REPORTING REQUIREMENTS AND DELIVERABLES The contractor shall provide monthly data transfer and calibration factors, and semi-annual and annual progress reports. ANTICIPATED PERIOD OF PERFORMANCE: One (1) year plus four (4) option years. OTHER IMPORTANT CONSIDERATIONS: (1) The Government is expected to use procedures in FAR Part 6.302-1 and (2) The North American Industry Classification System (NAICS) Code 541714 with a size standard of 1,000 employees. DISCLAIMER AND IMPORTANT NOTES This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. CONFIDENTIALITY No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). The proposed requirement was previously publicized under sources sought notice HHS-NIH-NIDA(AG)-SBSS-18-0523.