Mechanisms of Cognitive Fluctuations in ADRD Populations

Funding Opportunity Number: RFA-NS-25-014

Deadline: June 24, 2024


In order to facilitate unambiguous clinical outcomes in therapeutic trials for patients with AD/ADRDs who experience cognitive fluctuations, a clear understanding of the pathophysiology of these events, including the ability to track, predict, and ameliorate them, will be critical. The goal of this NOFO is therefore to invite research proposals that will elucidate the potential etiologies for these episodes. Applicants may propose to compare cognitive fluctuations across multiple AD/ADRD diagnostic categories (e.g., DLB vs VCID) or focus on one disorder, and may propose to investigate one or more potential mechanisms for these events. The patient population(s) in which cognitive fluctuations will be investigated should be thoroughly described with well-defined inclusion and exclusion criteria. The mechanism(s) proposed to underlie cognitive fluctuations in the identified population(s) should be clearly justified and capable of being measured in a rigorous fashion. Applications may include explorations of risk factors (e.g., genetic) that might predispose subjects to developing cognitive fluctuations, but the bulk of the research should concentrate on establishing a direct link between the events and the proposed mechanism in as close to real time as possible. Given that cognitive fluctuations typically occur unpredictably, continuous monitoring with an appropriate digital device is encouraged to maximize opportunities for capturing data at the onset, during, and after an episode occurs.

When appropriate, applicants are encouraged to leverage existing research resources for their studies. Such resources may include biospecimen samples from NIH-supported biorepositories (e.g., BioSEND, NCRAD or other existing biospecimen, imaging and data repositories (e.g., PDBP, NACC. Leveraging the infrastructure and/or resources of ongoing clinical trials or clinical studies supported through other Federal or private funds is also encouraged.

NINDS, as part of NIH, strives for rigor and transparency in all research it funds. For this reason, NINDS explicitly emphasizes the NIH application instructions related to rigor and transparency ( and provides additional guidance to the scientific community ( For example, the biological rationale for the proposed experiments must be based on rigorous and robust supporting data, which means that data should be collected via methods that minimize the risk of bias and be reported in a transparent manner. If previously published or preliminary studies do not meet these standards, applicants should address how the current study design addresses the deficiencies in rigor and transparency. Proposed experiments should likewise be designed in a manner that minimizes the risk of bias and ensures validity of experimental results.

For more information, please see the opportunity webpage.