Assessment of TBI-related ADRD Pathology Related to Cognitive Impairment and Dementia Outcomes (U01 - Clinical Trial Not Allowed) | RFA NS 24 003

Frequently Asked Questions (FAQs) - RFA NS 24 003 (NIH U01)

What is RFA NS 24 003?

RFA NS 24 003 is an NIH funding opportunity that uses a U01 cooperative agreement mechanism to support a coordinated, multisite research effort focused on the relationship between traumatic brain injury (TBI) and Alzheimer's disease and related dementias (ADRD). The emphasis is on understanding how TBI is linked to ADRD-relevant neuropathology and how those brain-based findings relate to real-world clinical outcomes such as cognitive impairment and dementia.

What is the main goal of this funding opportunity?

The central aim is to comprehensively characterize ADRD-relevant neuropathology in people with a history of TBI and connect neuropathological burden identified after death with antemortem symptoms and clinical presentation documented during life. In practice, the work is expected to link postmortem brain findings to cognitive trajectories, neuropsychiatric features, and dementia-related outcomes.

What type of award mechanism is used (and what does U01 mean here)?

This opportunity is a U01 cooperative agreement. Compared with a standard research project grant, a cooperative agreement typically involves substantial NIH programmatic involvement. Awardees should expect coordination expectations, milestone-driven progress, and collaboration requirements consistent with a multisite effort and shared-resource goals.

Are clinical trials allowed under this opportunity?

No. The opportunity is explicitly labeled "Clinical Trial Not Allowed." Applicants should not propose prospective interventional clinical trials under this NOFO.

What scientific questions is NIH expecting projects to address?

Projects are expected to clarify how TBI is associated with ADRD-related pathology and how that pathology corresponds to cognitive impairment and dementia outcomes. NIH also expects applicants to investigate why outcomes differ across individuals by examining both personal factors and injury-related factors that may modify neuropathology and clinical outcomes.

Which personal factors does the NOFO highlight as important to analyze?

The NOFO specifically calls for analyses that consider variables such as sex, age at the time of injury, time since injury, and social determinants of health. It also allows for other potentially important modifiers as appropriate to the research approach.

Which injury-related factors are emphasized?

NIH emphasizes careful characterization of injury severity and injury frequency. The NOFO recognizes that a single severe TBI and multiple repetitive TBIs may have different biological signatures and long-term consequences, and it expects projects to examine how these differences relate to neuropathology and dementia-related outcomes.

What role do brain banks play in this funding opportunity?

A brain-bank-centered approach is encouraged. The NOFO emphasizes comparing and harmonizing findings across participating sites and brain banks to strengthen the field's ability to identify which neuropathological features are most strongly associated with TBI history and which may reflect non-TBI pathways to dementia.

What does the NOFO expect regarding diagnosis prevalence and patterns in brain banks?

A major expected deliverable is improved clarity on the prevalence and patterns of TBI-associated neurodegenerative diagnoses within participating brain banks. This includes documenting the prevalence of TBI-related ADRD diagnoses and evaluating chronic traumatic encephalopathy (CTE) pathology, especially in the context of repetitive head impacts.

Is chronic traumatic encephalopathy (CTE) specifically mentioned?

Yes. The NOFO explicitly calls for evaluating CTE pathology, recognizing its relevance to repetitive head impacts and the need to understand how it relates to TBI history and neurodegenerative outcomes.

Should projects use existing samples, collect new samples, or both?

NIH signals strong interest in applications that combine retrospective resources with forward-looking sample acquisition. Competitive projects are expected to leverage existing retrospective samples (such as previously collected brain tissue and associated records) while also including plans to acquire new brain tissue specimens to expand the resource and address gaps in representation, exposure history, and clinical characterization.

What does "retrospective resources" mean in the context of this NOFO?

Within the information provided, "retrospective resources" refers to previously collected brain tissue and associated records already held by participating sites or brain banks that can be analyzed to address the NOFO goals.

What does NIH expect regarding antemortem clinical data?

Applicants are expected to incorporate methods for assessing antemortem symptomatology and clinical presentation. The NOFO stresses that neuropathology findings should not be interpreted in isolation; they should be linked to documented clinical outcomes observed during life, such as cognitive trajectories, neuropsychiatric features, and dementia-related outcomes.

How important is data sharing in this opportunity?

Data sharing is framed as a critical element of successful applications. The NOFO highlights broad sharing of clinical and neuropathological data as a key feature, rather than a minor administrative requirement.

Does the opportunity require building any specific sharing infrastructure?

Yes. Beyond standard data sharing, the NOFO specifically calls for developing a digital resource intended to support distribution and sharing of assessed neuropathological tissue. This suggests an expectation for scalable infrastructure that enables the broader research community to discover, access, and reuse harmonized information and potentially tissue-related outputs (for example, digitized pathology, standardized neuropathology assessments, or other shareable derivatives).

What kinds of harmonization or coordination are implied across sites?

The NOFO points toward cross-site harmonization, use of common data elements, and governance processes to enable responsible sharing while protecting privacy and maintaining scientific rigor. It also emphasizes comparing and harmonizing findings across sites to strengthen interpretability and consistency.

Who is eligible to apply?

Eligibility is broad and includes many U.S.-based organizations and governmental entities. Examples listed include state, county, and local governments; special districts; independent school districts; public housing authorities/Indian housing authorities; public and private institutions of higher education; federally recognized tribal governments and other tribal organizations; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other eligible entities.

Are specific institution types explicitly highlighted as eligible?

Yes. The NOFO explicitly highlights additional eligible applicant categories including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, regional organizations, and U.S. territories or possessions.

Can non-U.S. (foreign) organizations apply?

No. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply.

Are foreign collaborations allowed in any form?

Yes, in a limited way. While non-U.S. entities cannot apply as the applicant organization, foreign components (as defined by the NIH Grants Policy Statement) are allowed. This means a U.S. applicant may include certain eligible foreign collaborations when justified and compliant with NIH policy.

What are the CFDA numbers associated with this opportunity?

The opportunity is listed under CFDA numbers 93.853 and 93.866.

What is the maximum award amount mentioned?

The award ceiling shown is $1,300,000.

What is the closing date shown for this opportunity?

The original closing date shown is 2023-07-28.

What does "multisite" mean for applicants in practical terms?

Based on the description provided, "multisite" indicates the work is expected to be coordinated across multiple participating sites (such as brain banks or associated research groups). As a cooperative agreement, the project structure is expected to support collaboration, shared goals, harmonized methods, and milestone-driven progress across sites.

What outcomes are projects expected to connect to neuropathology findings?

Projects are expected to connect ADRD-relevant neuropathology and neuropathological burden with clinical outcomes observed during life, including cognitive impairment, dementia-related outcomes, cognitive trajectories, and neuropsychiatric features.

Does this opportunity focus only on a single type of TBI exposure?

No. The NOFO emphasizes both single severe TBI and repetitive TBIs, noting they may differ in biological signatures and long-term consequences. Applicants are expected to examine how injury severity and frequency influence pathology and outcomes.