Drug Development/Novel Targets: Mechanisms of non-pharmacological interventions

Initiate interdisciplinary research programs that integrate clinical, genomic and mechanistic research including cutting edge systems biology approaches to gain an in depth understanding of the mechanisms by which various non-pharmacological interventions impact brain health and the course of AD and AD-related dementias.

2030 RFA-AT-19-001: Promoting Research on Music and Health: Phased Innovation Award for Music Interventions (R61/R33) RFA-NS-19-008: Promoting Research on Music and Health: Fundamentals and Applications (R01) RFA-NS-19-009: Promoting Research on Music and Health: Fundamentals and Applications (R21) RFA-AT-23-009: Research Networks to Promote Multidisciplinary Mechanistic Studies on Music-Based Interventions for Pain or Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD) (U24 Clinical Trial Optional) 6.H In Progress Initiate interdisciplinary research programs that integrate clinical, genomic and mechanistic research... DN 2012 AD Summit: 5B, 5C, 5D, and 5F 2018 AD Summit: 1A Drug Development - Novel Targets 2016

  • Identification of at least 3 new therapeutic targets for neuroprotection based on knowledge of mechanisms mediating the impact of non-pharmacological interventions of brain health in aging, AD and AD-related dementias.
  • Preclinical proof-of-concept for at least 3 types of non-pharmacological interventions that can inform clinical trial design.

Summary of Key Accomplishments

NIA supports a growing portfolio of research evaluating how various non-pharmacologic interventions may reduce AD/ADRD-related risk factors and biomarkers. For example, NIA collaborated with the National Center for Complementary and Integrative Health to support development of research networks to promote multidisciplinary mechanistic studies of music-based interventions for both AD/ADRD and pain; one network focusing on music-based interventions for dementia is currently active.

Substantial NIA investment in non-pharmacological trials now support extensive efforts to rigorously test whether risk modification can effectively build cognitive resilience to prevent AD/ADRD. NIA also supports projects to evaluate the mechanisms underlying the effects of non-pharmacological interventions like exercise and specific dietary interventions on cognitive function and dementia. Of particular note are projects that support mechanistic interrogation of biosamples and data from participants of the landmark U.S. POINTER clinical trial. These ancillary studies are evaluating effects of the lifestyle interventions on: 1) biomarker trajectories through neuroimaging studies (R01AG062689); 2) vascular and neurovascular mechanisms (R01AG066910); 3) effects of sleep and sleep disturbances (R01AG064440); and 4) impact of diet on gut microbiome (U19AG063744).

The U.S. POINTER trial found that structured, high-intensity lifestyle interventions combining physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring improved cognition in older adults at risk of cognitive decline. These ancillary studies will help identify effectiveness of lifestyle strategies that could have important consequences for prevention of Alzheimer’s disease and related dementias and potential for translation to real-world settings.

The key accomplishments summary is current as of September 2025.