Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional) | PAR 25 065

Opportunity Information: Apply for PAR 25 065

The National Institutes of Health (NIH) is offering an R01 grant opportunity titled "Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01 Clinical Trial Optional)" under Funding Opportunity Number PAR-25-065. This announcement focuses on deepening the scientific understanding of why and how neuropsychiatric symptoms emerge in people living with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD). In plain terms, NIH is looking for rigorous studies that move beyond describing symptoms and instead explain the underlying mechanisms that produce them, with the long-range goal of opening new paths for treatment and prevention.

The central aim is to support research that clarifies the mechanisms associated with neuropsychiatric symptoms (NPS) in dementia. NPS is a broad umbrella that can include symptoms such as agitation, depression, anxiety, apathy, irritability, sleep and circadian disruption, hallucinations, delusions, and related behavioral changes that often appear during the course of AD/ADRD. These symptoms can be among the most distressing aspects of dementia for patients and caregivers, can accelerate functional decline, and frequently contribute to emergency care visits, institutionalization, and increased caregiver burden. NIH is signaling that it wants mechanistic work that can explain the pathways leading to these symptoms rather than only measuring how common they are or how severe they become.

A key feature of this opportunity is its emphasis on both biobehavioral and neurobiological pathways. Biobehavioral mechanisms can include factors such as stress biology, sleep and circadian rhythm dysregulation, pain, sensory impairment, social and environmental triggers, and caregiver-patient interaction dynamics, as well as how these factors interact with disease progression. Neurobiological mechanisms can include brain circuit dysfunction, neurotransmitter and neuroimmune changes, synaptic and network alterations, vascular contributions, and other brain-based processes relevant to the emergence of psychiatric and behavioral symptoms in dementia. NIH is especially interested in studies that can connect observable symptoms to underlying systems and pathways in a way that strengthens causal reasoning, improves prediction, or identifies points where intervention might realistically change outcomes.

Another major goal is translation: NIH expects that mechanistic findings will help identify novel therapeutic targets. That could mean uncovering specific biological processes, neural circuits, or modifiable behavioral and environmental drivers that can be targeted with new drugs, device-based approaches, behavioral interventions, or multimodal strategies. While the FOA does not limit applicants to any single type of approach, it makes clear that the research should contribute to intervention-relevant knowledge, meaning results should plausibly inform the development of strategies to treat NPS once they occur or prevent them from developing in the first place in people with AD/ADRD.

The mechanism of support is the R01 research project grant, and clinical trials are optional. That flexibility allows teams to propose basic-to-clinical mechanistic studies that may or may not include an intervention. For example, an application could focus on observational or experimental human studies designed to uncover mechanisms, or it could incorporate an intervention component if that is the best way to test a mechanistic hypothesis. The key is that the work should be aimed at mechanism, not simply symptom management without an explanatory framework.

Eligibility is broad and includes many types of U.S. organizations and some non-U.S. entities. Eligible applicants listed include state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (as long as they are not institutions of higher education); for-profit organizations other than small businesses; and small businesses. NIH also explicitly highlights additional eligible 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, and non-domestic (non-U.S.) entities (foreign organizations). This broad eligibility list suggests NIH is open to multidisciplinary and cross-sector proposals, including partnerships that reach diverse communities and care settings.

From an administrative standpoint, this is a discretionary grant in the health category, with CFDA numbers 93.242 and 93.866. The opportunity was created on 2024-11-18, and the listed application due date (original closing date) is 2026-09-07. The award ceiling and expected number of awards are not specified in the provided listing, which is common for some NIH FOAs where funding levels depend on the annual appropriation, program priorities, and the number of meritorious applications received.

Overall, this FOA is aimed at advancing the field from symptom description to mechanistic explanation for neuropsychiatric symptoms in Alzheimer's dementia and related dementias. NIH is looking for strong, hypothesis-driven work that can clarify how biobehavioral and neurobiological processes lead to NPS, and that can ultimately point toward new, testable therapeutic targets that could improve quality of life for people living with dementia and reduce the burden on families and care systems.

• 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 (R01 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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