Clarifying the Relationship between Delirium and Alzheimers Disease and Related Dementias (R21/R33) | PAR 17 037

Opportunity Information: Apply for PAR 17 037

The NIH grant opportunity "Clarifying the Relationship between Delirium and Alzheimers Disease and Related Dementias (R21/R33)" (Funding Opportunity Number PAR 17-037; CFDA 93.866) supports health research aimed at sorting out how delirium and Alzheimers disease and related dementias (ADRD) are biologically and clinically connected. The central motivation is a two-way problem seen in real-world care: people who already have ADRD appear to be more likely to develop delirium and often have worse outcomes when delirium occurs, while people who experience delirium (even if they did not previously have diagnosed dementia) are more likely to go on to develop mild cognitive impairment or ADRD and may decline cognitively faster than comparable patients who never had delirium. The FOA is designed to move beyond simply documenting that these associations exist and instead push applicants to explain why they happen, including the mechanisms, pathways, and patient factors that create this bidirectional risk.

Projects responsive to the announcement can approach the delirium-ADRD relationship from multiple angles. The FOA highlights studies that investigate whether delirium and ADRD share common underlying pathways, whether the conditions unfold in a sequential way (one setting the stage for the other), and whether the relationship could be causative, contributory, or synergistic. This includes work that examines shared biology such as inflammation, vascular injury, neurotransmitter disruption, network connectivity changes, or other neurodegenerative and systemic processes that might make a brain more vulnerable to acute delirium or accelerate longer-term neurocognitive decline after a delirium episode. The FOA also explicitly encourages mechanistic research on how delirium emerges on the background of aging and neurodegeneration, and it calls out the value of appropriate animal models for teasing apart cause-and-effect and testing hypotheses that are difficult to isolate in human studies.

The announcement also welcomes research that identifies risk factors that influence who develops delirium when they already have ADRD, and who develops subsequent cognitive impairment or ADRD after delirium. That can include clinical risk factors (comorbidities, medications, frailty, sensory impairment), biological markers, genetic factors, perioperative or hospital exposures, and social or environmental contributors. Another major theme is improving how each condition is diagnosed and assessed in the presence of the other, since delirium can be hard to recognize in someone with baseline cognitive impairment, and dementia can be hard to diagnose accurately after a delirium episode. Relatedly, applicants can propose studies that define meaningful phenotypes (subtypes) among patients with both conditions, which could lead to better prediction, more tailored management, and clearer outcomes for clinical trials.

In addition to observational and mechanistic work, the FOA supports testing interventions, including both pharmacologic and non-pharmacologic strategies, to prevent delirium, treat it, or reduce its downstream impact in patients with ADRD, as well as strategies aimed at preventing or mitigating longer-term cognitive decline and dementia risk after delirium. In practice, this could include hospital-based or perioperative delirium prevention bundles, targeted medication approaches, sleep and circadian interventions, mobility and rehabilitation protocols, caregiver-mediated strategies, or other care models that reduce delirium burden and improve longer-term cognition and function. Across all these possible project types, the unifying goal is to generate mechanistic insight that improves risk assessment, diagnosis, patient stratification/phenotyping, prevention, and management for both delirium and ADRD.

The mechanism specified is R21/R33, which generally signals a phased approach where early, exploratory work (R21) can transition to a second phase (R33) to expand or further validate findings once pre-specified milestones are met. The FOA is categorized as a discretionary grant in the health area and is administered by the National Institutes of Health. A wide range of organizations are eligible to apply, including federal, state, county, city, and special district governments; public and private institutions of higher education; independent school districts; public housing authorities; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and tribal governments and tribal organizations. The FOA also explicitly lists additional eligible applicant categories such as Historically Black Colleges and Universities, Hispanic-serving Institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions, faith-based or community-based organizations, U.S. territories or possessions, and even non-U.S. entities and regional organizations, reflecting an intent to encourage broad participation.

Key administrative details provided include an original closing date of January 24, 2018, and a creation date of October 27, 2016. The award ceiling and expected number of awards are not specified in the provided listing. Overall, the opportunity is aimed at building a clearer, biologically grounded and clinically actionable understanding of how delirium and ADRD interact, with the expectation that better mechanistic clarity will translate into better detection, prevention, and treatment strategies for patients affected by either or both conditions.

• 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)" 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 2016-10-27.
• Applicants must submit their applications by 2018-01-24. (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.

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