Mechanistic and Hemodynamic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID)(R01 - Clinical Trial Not Allowed) | PAR 24 196

Opportunity Information: Apply for PAR 24 196

This NIH funding opportunity (PAR-24-196) supports R01 research projects focused on understanding the mechanistic and hemodynamic drivers of diffuse white matter disease as it relates to vascular contributions to cognitive impairment and dementia (VCID). The program is motivated by the fact that diffuse white matter disease is extremely common in older adults and is repeatedly linked in clinical studies to later-life cognitive decline and dementia in both men and women. On brain imaging, it is often seen as white matter hyperintensities on MRI or as signal changes on CT, and it can also be confirmed with histology in human tissue or in animal models. Even though clinicians encounter these lesions frequently, the field still lacks a clear, detailed explanation of why they develop, why certain brain regions are more vulnerable than others, how the disease progresses over time, and what it does to the function of axons and neural circuits.

The scientific focus is on basic and translational mechanistic work rather than testing treatments in people. The FOA highlights that diffuse white matter disease likely reflects a mixture of pathologies, including demyelination and/or loss of white matter fibers driven by multifocal infarction and chronic local ischemia. It is commonly associated with arteriosclerosis of deep penetrating arteries and may co-occur with small infarcts in structures such as the basal ganglia, brainstem, or cerebellum. While periventricular white matter is a classic location, subcortical white matter can also be affected. A central theme of the announcement is the need to connect vascular and blood flow related problems (hemodynamics, perfusion deficits, vessel disease) to downstream cellular and molecular injury mechanisms in white matter, and then link those injuries to tissue-level and circuit-level dysfunction that could plausibly explain cognitive symptoms.

Projects responsive to this opportunity would be expected to dig into biological mechanisms at multiple scales, including molecular pathways, cellular responses (for example, oligodendrocytes, myelin maintenance, axonal integrity, glial and vascular cell interactions), tissue vulnerability patterns across brain regions, and the consequences for neural signaling and network behavior. The FOA emphasizes that the physiological impact of diffuse white matter disease on local axons and circuit function remains largely unknown, so studies that clarify how these lesions disrupt communication in the brain and contribute to cognitive impairment fit the program’s stated gaps. The long-term aim is foundational knowledge that can guide future prevention and intervention strategies to reduce the public health burden of VCID, rather than immediate clinical testing.

Administratively, this is a discretionary NIH grant using the R01 mechanism, and clinical trials are not allowed under this announcement. The opportunity is a reissue of prior NIH solicitations in this scientific area (RFA-NS-16-021, PAR-18-413, RFA-NS-19-039), signaling a continued programmatic push to build a stronger mechanistic understanding of age-related cerebrovascular and white matter disease. The listed application due date is 2024-10-04, and the opportunity includes an award ceiling of $500,000 (as provided in the source information).

Eligibility is broad and includes many common U.S. applicant types such as public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and various levels of government (state, county, city/township, special districts), as well as independent school districts and public housing authorities/Indian housing authorities. It also explicitly calls out several categories of institutions and organizations that are often emphasized for inclusive participation, including HBCUs, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions, along with faith-based or community-based organizations and certain tribal governments and regional organizations. Foreign (non-U.S.) entities are not eligible to apply, and non-U.S. components of U.S. organizations are not eligible; however, foreign components, as defined by NIH policy, are allowed, meaning a U.S.-based applicant may include certain well-justified international elements within the project structure if they meet NIH’s definition and requirements. The CFDA numbers associated with this opportunity are 93.853 and 93.866, both under the NIH health research assistance umbrella.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mechanistic and Hemodynamic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID)(R01 - Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2024-04-05.
• Applicants must submit their applications by 2024-10-04. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 24 196

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