Emotional Function in Normal Aging and/or MCI and AD/ADRD (R21 - Clinical Trial Not Allowed) | PAR 18 582

Frequently Asked Questions (FAQs)

What is the main focus of NIH PAR-18-582?

PAR-18-582 supports exploratory, early-stage research to understand how emotional functioning changes across later life. It covers both typical (normal) aging and aging in the context of mild cognitive impairment (MCI), Alzheimer's disease (AD), and Alzheimer's disease-related dementias (AD/ADRD). A central aim is to map emotional trajectories over time and identify neurobiological and brain-behavior mechanisms that shape those trajectories in healthy aging and become disrupted in early disease.

What types of emotional processes does the FOA emphasize?

The FOA highlights multiple components of emotional functioning, including emotion perception, emotional reactivity, emotion regulation strategies, and affective decision-making. It encourages work that clarifies how these processes may shift across adulthood into older age.

Why does the FOA emphasize “trajectories” of emotional change?

Foundational aging research suggests many older adults maintain stable or even improved emotional well-being compared with younger adults. This opportunity pushes beyond that broad observation by encouraging studies that map how emotional functioning changes over time (the shape and timing of change), rather than relying only on cross-sectional comparisons or general statements about age differences.

What does the FOA mean by “mechanism”?

A key theme is linking emotional outcomes to underlying neurobiological and neural-behavioral pathways. The FOA prioritizes projects that connect changes in emotion processing and regulation to measurable neural factors (such as patterns of brain activity, connectivity, or other neurobiological indicators), rather than only describing emotional symptoms.

How does the FOA address normal aging versus MCI and early AD/ADRD?

The FOA is structured to sharpen distinctions between emotional functioning in normal aging and emotional changes that may emerge in MCI and early AD/ADRD. It encourages studies that examine how integrated neural and behavioral systems supporting emotional functioning may begin to operate differently as neurodegenerative changes start, potentially before more severe clinical impairment occurs.

Does this opportunity include research on neuropsychiatric symptoms in dementia?

Yes. The FOA encourages projects that connect emotion-related dysfunction to neuropsychiatric symptoms commonly seen in AD/ADRD. Examples mentioned include anxiety, depression, irritability, apathy, agitation, and other behavioral and psychological symptoms of dementia. The idea is that problems in emotional processing and regulation may help explain how and why these symptoms arise.

What is the three-goal scientific structure described in the FOA?

The FOA describes three interconnected goals: (1) characterize normative developmental or maturational shifts in emotional processes with aging, (2) examine how breakdowns in neural and behavioral systems supporting emotional functioning may emerge in MCI and early AD/ADRD, and (3) link emotion-related dysfunction to neuropsychiatric symptoms common in AD/ADRD.

What grant mechanism is used for this funding opportunity?

This opportunity uses the NIH R21 Exploratory/Developmental Grant mechanism, which is intended for high-potential projects in early, conceptual, or pilot phases, including new ideas, methods, or emerging lines of inquiry.

What is the funding cap mentioned for this R21?

The posted award ceiling is $200,000.

Are clinical trials allowed under this FOA?

No. The FOA is labeled “Clinical Trial Not Allowed.” Proposed studies must not be designed as clinical trials, meaning they cannot prospectively assign human participants to an intervention to evaluate effects on health-related outcomes.

If clinical trials are not allowed, can studies still involve human participants?

Yes. Projects can involve human participants, including clinically relevant populations such as individuals with MCI or early AD/ADRD, as long as the work is not an interventional clinical trial. The FOA frames allowable work as observational, mechanistic, measure-development oriented, or otherwise non-interventional in the clinical trial sense.

What kinds of studies are encouraged if interventions cannot be tested?

The FOA encourages mechanistic and trajectory-focused studies that examine emotion processing and regulation alongside neural factors. It also supports work that clarifies differences between normal aging and early disease. While direct intervention testing is outside scope, the expectation is that mechanistic findings can identify targets for future prevention or intervention efforts.

What populations are relevant to this FOA?

The FOA is relevant to older adults experiencing typical aging as well as people along the aging-to-dementia continuum, including those with MCI and early AD/ADRD. It also emphasizes understanding emotional functioning in relation to neuropsychiatric symptoms seen in AD/ADRD.

What is meant by “brain-behavior mechanisms” in this context?

In this FOA, brain-behavior mechanisms refer to the relationships between neural systems involved in emotion processing and regulation and the observable emotional outcomes or behaviors. The FOA specifically highlights interest in how emotion-related brain systems, and their interaction with cognition, may change in normal aging and become disrupted in MCI and early AD/ADRD.

What types of organizations are eligible to apply?

Eligibility is broad and includes many types of U.S. organizations and institutions, such as public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and state/county/local governments and certain housing authorities.

Does the FOA encourage applications from specific institution types?

Yes. The FOA explicitly welcomes applications from mission-driven and community-rooted organizations and institutions, including Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs).

Are tribal organizations and U.S. territories eligible?

Yes. Eligible applicants include certain tribal organizations and governments, as well as U.S. territories or possessions.

Are faith-based or community-based organizations eligible?

Yes. The FOA includes faith-based or community-based organizations among eligible applicant types.

Can non-U.S. (foreign) organizations apply?

Yes. The FOA indicates that non-U.S. entities (foreign organizations) are included among eligible applicants.

How does this FOA relate to future interventions if trials are not allowed?

Although clinical trials are not permitted, the FOA is designed to produce mechanistic insights and clearer distinctions between normal aging and early disease-related changes. These findings are intended to identify novel targets that could later inform prevention or intervention strategies aimed at reducing emotion dysregulation, strengthening emotional resilience, or addressing neuropsychiatric symptoms across the aging-to-dementia continuum.