Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21 Clinical Trial Optional)
This grant seeks research into the biological and behavioral causes of neuropsychiatric symptoms in Alzheimer's patients to identify new treatment targets.
This grant is no longer accepting proposals
National Institutes of Health has archived this opportunity.
Funder: National Institutes of Health (NIH)
Due Dates: October 16, 2025 (New) | November 16, 2025 (Renewal/Resubmission) | February 16, 2026 (New) | March 16, 2026 (Renewal/Resubmission) | June 16, 2026 (New) | July 16, 2026 (Renewal/Resubmission)
Funding Amounts: Up to $275,000 total direct costs over 2 years, with no more than $200,000 in any single year.
Summary: Supports exploratory research to elucidate neurobiological and behavioral mechanisms underlying neuropsychiatric symptoms in Alzheimer's disease and related dementias to identify novel therapeutic targets.
Key Information: Clinical trial optional; encourages high-risk/high-reward projects without preliminary data; data sharing via NIH repositories required.
Description
This funding opportunity encourages exploratory and developmental research aimed at understanding the mechanisms behind neuropsychiatric symptoms (NPS) in individuals with Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD). NPS include symptoms such as aggression, psychosis, anxiety, apathy, depression, agitation, sleep disturbances, and wandering, which significantly impact patient care and accelerate functional decline.
The goal is to advance mechanistic knowledge of biobehavioral and neurobiological pathways leading to NPS, thereby identifying novel therapeutic targets for treatment and prevention. Research may include basic neuroscience, translational studies, neuroimaging, neurophysiology, gene expression, epigenetics, and behavioral interventions. Studies clarifying mechanisms of action of existing treatments or identifying biomarkers of treatment response are also encouraged, provided they fit the NIH mechanistic clinical trials framework.
The announcement promotes the use of dimensional constructs, such as those from the NIMH Research Domain Criteria (RDoC) initiative, to assess NPS across multiple levels of analysis rather than relying solely on traditional diagnostic categories. It supports integration of epidemiologic, genomic, and mechanistic research, including systems biology approaches, and encourages studies on diverse populations and sex differences.
Examples of research interests include:
- Neural circuits involved in NPS and comparisons with other neuropsychiatric diseases.
- Circadian rhythm disruptions related to agitation and disruptive behaviors.
- Molecular mechanisms underlying NPS, including gut-brain axis and microbiome roles.
- Use of digital technologies and machine learning to characterize behavioral patterns and environmental triggers.
- Development of clinically meaningful outcome measures and biomarkers.
- Distinguishing NPS due to unmet medical or social needs.
This FOA uses the R21 exploratory/developmental grant mechanism, suitable for high-risk/high-reward projects that may lack preliminary data. Clinical trials are optional but must focus on mechanistic understanding rather than safety or efficacy testing.
