Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) | PAR 25 064

Opportunity Information: Apply for PAR 25 064

The National Institutes of Health (NIH) is offering a discretionary grant opportunity titled "Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional)" under funding opportunity number PAR-25-064. This announcement uses the R21 mechanism, which is typically designed to support early-stage, exploratory, or high-risk/high-reward studies that can open up new research directions. The central aim is to fund projects that deepen scientific understanding of the mechanisms that drive neuropsychiatric symptoms in people living with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD). Neuropsychiatric symptoms in this context commonly include issues such as agitation, depression, anxiety, apathy, irritability, sleep and circadian disturbances, hallucinations, delusions, and related behavioral changes that can be distressing for patients and caregivers and often complicate care.

The focus of the opportunity is on mechanism-oriented research rather than purely descriptive work. NIH is explicitly encouraging studies that clarify the pathways leading to NPS, including both biobehavioral and neurobiological mechanisms. In practical terms, that means projects might investigate how changes in brain circuitry, neurotransmitter systems, neuroinflammation, vascular injury, synaptic dysfunction, stress physiology, sleep disruption, or other biological processes contribute to the emergence or worsening of behavioral and psychological symptoms in AD/ADRD. At the same time, the FOA highlights biobehavioral pathways, which can include interactions among behavior, environment, caregiving context, social factors, and physiology, as well as how these interact with underlying neurodegenerative processes. The expectation is that funded studies will move the field closer to an integrated, mechanistic understanding of why NPS occur, how they progress, and why they vary so widely across individuals.

A major intended payoff of this research is the identification of novel therapeutic targets. By pinpointing causal or strongly contributing mechanisms, applicants can help set the stage for developing more effective interventions to treat NPS or prevent them from developing in the first place. The announcement is "clinical trial optional," meaning applicants may propose studies that include a clinical trial component if appropriate, but they are not required to do so. This flexibility supports a range of approaches, from preclinical or translational mechanistic studies to human-centered investigations that may involve interventions, experimental manipulations, or proof-of-concept trials designed to test mechanistic hypotheses.

Eligibility is broad and includes many organization types that commonly apply to NIH research grants. Eligible applicants include state, county, and local governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments; Native American tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofit organizations (both 501(c)(3) and non-501(c)(3), excluding institutions of higher education in those categories); for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly calls out additional eligible applicant groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, tribal governments other than federally recognized entities, and non-U.S. entities (foreign organizations). This breadth signals an interest in attracting diverse perspectives, populations, and research settings, which is especially relevant for AD/ADRD where symptom expression, access to care, and caregiver burden can differ across communities.

From the published source details, the activity category is Health and the CFDA numbers listed are 93.242 and 93.866. The opportunity was created on 2024-11-18, and the original closing date is 2026-09-07. The award ceiling and expected number of awards are not specified in the provided listing, which usually means applicants should consult the full FOA text on NIH or Grants.gov for budget limits, project period expectations, and any institute-specific guidance. Overall, the announcement is aimed at accelerating new mechanistic insights into neuropsychiatric symptoms in AD/ADRD in ways that can directly inform next-generation strategies for treatment and prevention.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.866.
• This funding opportunity was created on 2024-11-18.
• Applicants must submit their applications by 2026-09-07. (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.

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