Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional) | PAR 20 159

Opportunity Information: Apply for PAR 20 159

This funding opportunity, titled "Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional)" (PAR 20-159), is a National Institutes of Health (NIH) discretionary grant program in the health category (CFDA 93.242). Its central purpose is to support early-stage, innovative research that digs into the underlying mechanisms that drive neuropsychiatric symptoms in people living with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD). In practical terms, the FOA is aimed at studies that move beyond simply describing symptoms and instead clarify how and why symptoms emerge, worsen, or vary across individuals, with an emphasis on producing mechanistic insights that can ultimately inform better prevention and treatment strategies.

The scientific focus is specifically on mechanisms linked to neuropsychiatric symptoms (NPS) in dementia, which commonly include problems such as agitation, aggression, depression, anxiety, apathy, sleep disruption, psychosis, irritability, and other behavioral or emotional changes that often accompany cognitive decline. The FOA emphasizes that successful applications should strengthen mechanistic understanding across both biobehavioral and neurobiological pathways. That framing signals interest in work that can connect behavior and clinical presentation to measurable biological, physiological, neural circuit, genetic, molecular, or systems-level processes, as well as studies that examine how environmental, caregiving, social, or behavioral factors interact with brain changes to produce NPS. The expected payoff is clearer causal or contributory models of NPS in AD/ADRD rather than purely correlational findings.

A major theme in the announcement is translation potential: by identifying and validating mechanisms, the funded projects are expected to point toward novel therapeutic targets. Even if a given study is not itself a full intervention trial, the goal is that it will generate evidence strong enough to justify future intervention development, including treatments intended to reduce existing neuropsychiatric symptoms or prevent their onset as dementia progresses. The "Clinical Trial Optional" designation means applicants may propose either non-clinical-trial mechanistic studies or clinical trials, depending on what best fits the mechanistic question. This provides flexibility for projects that might include experimental manipulations, proof-of-concept testing, or other designs that meet the NIH definition of a clinical trial, while still keeping the core emphasis on mechanism.

The grant mechanism is an R21, which is typically used by NIH to support exploratory and developmental research projects that are high-risk/high-reward, generate preliminary data, or test novel hypotheses. The opportunity lists an award ceiling of $200,000, aligning with the smaller, pilot-style scope common to R21 projects. While the listing does not specify the number of expected awards, the intent is clearly to seed innovative mechanistic work that can later be expanded into larger projects or intervention programs if findings are compelling.

Eligibility is broad and includes many types of U.S. domestic organizations and, notably, some non-U.S. participation as well. 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; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofit organizations both with and without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly 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 agencies; U.S. territories or possessions; regional organizations; and non-domestic (non-U.S.) entities (foreign organizations). This breadth suggests an interest in attracting diverse research teams and settings, potentially including community-based or underserved populations where NPS burden and care challenges can be substantial.

Key administrative details in the listing include the NIH as the sponsoring agency, the creation date of March 31, 2020, and an original closing date of May 7, 2023. Overall, the opportunity is best understood as a targeted NIH initiative to accelerate discovery of the biological and biobehavioral drivers of neuropsychiatric symptoms in AD/ADRD, with the explicit expectation that clearer mechanisms will open doors to new, more effective therapeutic approaches for patients and caregivers dealing with some of the most disruptive and distressing aspects of dementia.

• 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.
• This funding opportunity was created on 2020-03-31.
• Applicants must submit their applications by 2023-05-07. (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 $200,000.00 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.

Apply for PAR 20 159

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