Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) | PAR 23 208

Opportunity Information: Apply for PAR 23 208

The National Institutes of Health (NIH) is soliciting applications under Funding Opportunity Announcement PAR-23-208, titled "Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional)." This is a discretionary grant opportunity in the health area (CFDA 93.242 and 93.866) using the R21 mechanism, which is generally geared toward early-stage, exploratory, or high-impact concept studies that can generate strong preliminary data and clarify feasibility for future, larger projects. The central purpose of the FOA is to fund research that deepens understanding of the mechanisms underlying neuropsychiatric symptoms in people living with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD), with an emphasis on uncovering pathways that could eventually point to new therapeutic targets.

The scientific focus is specifically on neuropsychiatric symptoms (NPS) that frequently occur in AD/ADRD and can be among the most distressing and disabling aspects of dementia for patients and caregivers. While the announcement text does not list particular symptoms, NPS in this context commonly includes issues such as agitation, depression, anxiety, apathy, irritability, sleep disturbances, and psychosis-like symptoms, which can worsen quality of life, increase caregiver burden, and contribute to earlier institutionalization. The FOA is framed around advancing mechanistic knowledge, meaning proposed projects should go beyond describing symptoms or documenting prevalence and instead aim to explain why these symptoms emerge and how they are biologically and behaviorally generated in AD/ADRD.

A key feature of this opportunity is its interest in both biobehavioral and neurobiological mechanisms. In practice, that can include studies that connect behavior and clinical presentation to brain circuitry changes, neurotransmitter and neuromodulator disruptions, immune and inflammatory pathways, neuroendocrine stress systems, sleep and circadian biology, vascular contributions, genetics and epigenetics, and other disease-related processes that may drive or modulate NPS. The overall expectation is that the resulting findings will help map the pathways leading to NPS, clarify causal or contributing factors, and identify leverage points that could be translated into intervention strategies. Importantly, the FOA explicitly notes that mechanistic discoveries may provide insight into novel therapeutic targets that can be advanced into future interventions aimed at treating NPS or preventing their development in AD/ADRD.

The announcement is labeled "Clinical Trial Optional," which signals flexibility in study design. Applicants may propose projects that do not involve a clinical trial (for example, mechanistic observational studies, experimental medicine approaches without a trial, biomarker-focused work, or human and animal translational studies), or they may propose a clinical trial if it is appropriate for testing a mechanistic hypothesis or target engagement concept. The unifying requirement is that the study should materially advance mechanistic understanding of NPS in the context of AD/ADRD, rather than focusing only on symptomatic management without a clear link to underlying pathways.

On the funding details provided, the award ceiling is listed as $275,000. The opportunity lists an original closing date of 2026-09-07. The record does not specify the number of expected awards in the provided fields, but the mechanism and scope suggest a competitive, proposal-driven process where awards depend on scientific merit and program priorities.

Eligibility is broad and inclusive, spanning many organization types. Eligible applicants include state, county, city/township, and 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; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; small businesses; and other categories. The FOA also highlights additional eligible applicant types such as Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and 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 government agencies; regional organizations; U.S. territories or possessions; and non-U.S. entities (foreign organizations). This broad eligibility indicates NIH interest in attracting diverse perspectives, settings, and study populations, including community-based and underserved contexts, as well as international expertise where relevant.

Taken together, this FOA is best understood as a targeted call for innovative, mechanism-forward research on the neuropsychiatric dimensions of Alzheimer's and related dementias. It aims to move the field beyond describing NPS and toward explaining the biological and biobehavioral processes that produce them, with the longer-term goal of catalyzing new, mechanism-based therapeutic strategies to treat or prevent these symptoms in people living with AD/ADRD.

• 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 2023-06-14.
• 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.)
• Each selected applicant is eligible to receive up to $275,000.00 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.

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