Mechanism-Focused Research to Promote Adherence to Healthful Behaviors to Prevent Mild Cognitive Impairment (MCI) and Alzheimers Disease and Related Dementias (AD/ADRD) (R61/R33 Clinical Trial Required) | RFA AG 22 016

Opportunity Information: Apply for RFA AG 22 016

This NIH funding opportunity (RFA-AG-22-016) supports mechanism-focused research aimed at improving long-term adherence to healthful behaviors that could help prevent cognitive decline, mild cognitive impairment (MCI), and Alzheimers disease and related dementias (AD/ADRD). The central idea is that many lifestyle and prevention programs show promise, but they only work if people can realistically start them and, more importantly, stick with them over time. Because of that, the FOA is focused less on whether a given behavior is generally "good" (like exercise, diet change, sleep improvement, or cognitive training) and more on identifying the modifiable, meaningful factors that cause better adherence and maintenance in real life, across different people and contexts.

The research emphasis is on understanding how, why, and for whom behavior change interventions work by testing specific psychological and interpersonal mechanisms. In other words, applicants are expected to go beyond simply delivering an intervention and reporting outcomes. Projects should isolate particular features of an intervention (for example, accountability structures, motivational components, social support formats, feedback and self-monitoring tools, habit formation strategies, or stress and emotion regulation elements) and evaluate how those features activate measurable processes that drive adherence. The FOA is looking for mechanisms that are both actionable (something you can actually manipulate in an intervention) and plausibly causal (supported by study designs and analyses that can show that changing the mechanism changes adherence).

The program uses the R61/R33 phased innovation mechanism and requires a clinical trial. The R61 phase is typically used for early, milestone-driven work where investigators develop, refine, and "de-risk" an approach by demonstrating feasibility and showing that the intervention can engage the proposed target mechanism. If predefined milestones are met, the project can transition to the R33 phase, which supports a more rigorous test of the intervention and the mechanism, generally with stronger designs, clearer outcome assessment, and a closer look at how durable adherence is over time. The phased structure is meant to prevent projects from jumping straight into large trials before the intervention is sufficiently optimized or before there is evidence that the intended mechanism can be reliably engaged.

Applications are expected to be framed within the NIH Stage Model for behavioral intervention development (including Stages I through IV). That means the FOA is open to a range of maturity levels, from early-stage work that builds and refines interventions (Stage I) to more advanced studies that test them under real-world conditions and evaluate implementation-related issues (later stages, including Stages II through IV). Regardless of stage, the throughline is that the project should be mechanism-centered: it should clearly specify the adherence problem being addressed, the hypothesized mechanism(s) at the individual and/or interpersonal level, how the intervention will manipulate those mechanisms, and how the study will measure whether the mechanisms were engaged and whether that engagement explains adherence and downstream cognitive health-related outcomes.

Interventions can target adherence to lifestyle behavior patterns as well as other prevention-relevant approaches, with cognitive training explicitly mentioned as an example. The FOA also encourages integrating basic science questions, meaning it supports studies that connect foundational psychological and interpersonal processes to practical intervention design. This includes work aimed at making approaches more effective, more efficient, and more personalized, such as identifying which mechanisms matter most for which subgroups, tailoring intervention components to an individuals barriers and facilitators, or optimizing interventions so they require fewer resources while still producing meaningful adherence.

From an eligibility and participation standpoint, NIH lists a broad set of eligible applicants. This includes many types of U.S. government entities (state, county, city/township, special districts), public and private institutions of higher education, independent school districts, federally recognized tribal governments, tribal organizations that are not federally recognized, public housing authorities, nonprofits with or without 501(c)(3) status, for-profit organizations (other than small businesses), and small businesses, among others. The FOA also highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, faith-based or community-based organizations, U.S. territories or possessions, and even non-U.S. (foreign) organizations and regional organizations, reflecting an interest in diverse settings and populations relevant to aging and dementia prevention research.

Administratively, the opportunity is offered by the National Institutes of Health under the health funding activity category (CFDA 93.866). The original closing date listed is September 15, 2021, and the notice describes it as a discretionary grant opportunity using the R61/R33 mechanism. While an award ceiling and expected number of awards are not specified in the provided summary, the key programmatic expectation is clear: propose a clinical trial that uses a phased, milestone-based plan to develop and test interventions that improve adherence by targeting well-defined, measurable, and modifiable psychological or interpersonal mechanisms tied to prevention of cognitive decline, MCI, and AD/ADRD.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Mechanism-Focused Research to Promote Adherence to Healthful Behaviors to Prevent Mild Cognitive Impairment (MCI) and Alzheimers Disease and Related Dementias (AD/ADRD) (R61/R33 Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.866.
• This funding opportunity was created on 2021-04-06.
• Applicants must submit their applications by 2021-09-15. (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.

Apply for RFA AG 22 016

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