Clarifying the Relationship between Delirium and Alzheimers Disease and Related Dementias (R21/R33 Clinical Trial Optional) | PAR 18 181

Opportunity Information: Apply for PAR 18 181

This NIH grant opportunity (PAR-18-181) supports research aimed at untangling how delirium and Alzheimer's disease and related dementias (ADRD) influence one another. The core problem the FOA targets is the two-way relationship seen in clinical care: people who already have ADRD tend to be more vulnerable to delirium and often do worse when delirium occurs, while people who develop delirium (often during hospitalization, surgery, critical illness, or acute infection) appear more likely to develop later mild cognitive impairment or ADRD and may decline faster than similar patients who never became delirious. The opportunity is meant to move beyond simple association by generating evidence about mechanisms and pathways that explain why these patterns occur and how they can be identified earlier and managed better.

The FOA encourages projects that clarify whether delirium and ADRD share biological pathways, whether one condition accelerates or unmasks the other, or whether both arise from overlapping vulnerabilities such as aging-related brain changes, neurodegeneration, inflammation, vascular injury, synaptic dysfunction, or impaired brain resilience. A major emphasis is on mechanistic insight: studies can look for common, sequential, causative, contributory, or synergistic mechanisms linking delirium and ADRD, including research that examines how acute physiologic stressors interact with an already vulnerable or degenerating brain. The announcement explicitly welcomes work that uses appropriate animal models to study how delirium-like states emerge in the context of aging and neurodegeneration, since experimental models can help isolate triggers and biological cascades that are hard to disentangle in human studies.

Beyond mechanisms, the FOA highlights several practical research directions. One is identifying risk factors that predict delirium onset or worsening among people with ADRD and, conversely, identifying features of delirium that predict later cognitive impairment or dementia. Another is improving diagnosis and assessment when the two conditions overlap, since delirium can be difficult to recognize in someone with pre-existing cognitive impairment, and dementia can be missed or mischaracterized during or after an acute delirium episode. The FOA also supports efforts to define meaningful phenotypes among patients who experience both conditions, for example, subtypes based on symptom profiles, biomarker patterns, precipitants, course and recovery, or differential response to interventions. Finally, the opportunity allows for testing pharmacologic and non-pharmacologic strategies that prevent delirium, treat it, or reduce its downstream impact in patients with ADRD, and likewise strategies that might reduce dementia risk or progression in patients who have experienced delirium. Clinical trials are optional, meaning applicants may propose observational, mechanistic, translational, or interventional work depending on the scientific question.

The funding mechanism is the R21/R33, which is typically used for phased innovation: an early exploratory stage (R21) that can transition to a larger, more definitive stage (R33) if milestones are met. In practice, this structure fits projects where preliminary mechanistic signals, feasibility, or initial phenotyping must be demonstrated before scaling to more extensive validation, longitudinal follow-up, or broader intervention testing. The overall intent is to produce results that improve risk assessment, detection, phenotyping, prevention, and clinical management for both delirium and ADRD, with the long-term goal of reducing poor outcomes such as prolonged cognitive decline, loss of independence, and increased morbidity and mortality.

Administrative details in the source indicate this is a discretionary NIH grant opportunity in the health category (CFDA 93.866). Eligibility is broad and includes many types of U.S. institutions and organizations: state, county, and local governments; public and private institutions of higher education; federally recognized tribal governments and certain tribal organizations; nonprofits (with or without 501(c)(3) status); for-profit organizations (other than small businesses) as well as small businesses; and other entities. The FOA also notes additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving institutions, HBCUs, tribally controlled colleges and universities, faith-based or community-based organizations, U.S. territories or possessions, and even non-U.S. (foreign) entities and regional organizations. The original closing date listed in the provided data is January 7, 2020, and no award ceiling or expected number of awards is specified in the excerpt.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Clarifying the Relationship between Delirium and Alzheimers Disease and Related Dementias (R21/R33 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.866.
• This funding opportunity was created on 2017-11-01.
• Applicants must submit their applications by 2020-01-07. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 18 181

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