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Increase investment in clinical trials that robustly test a variety of lifestyle and other non-pharmacological interventions. Employ precision medicine research principles in non-pharmacologic intervention studies by incorporating deep molecular profiling and digital/wearable technologies for tracking responsiveness to the intervention.
2026 PAR-14-089: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-16-365: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-18-175: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-18-877: Early Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-16-364: Late Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-18-028: Late Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) PAR-18-878: Late Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (R01) 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) PAR-19-298: Non-Invasive Neurostimulation in AD/ADRD (R01) PAR-18-878: Late Stage Clinical Trials for the Spectrum of Alzheimer’s Disease and Age-related Cognitive Decline (R01 Clinical Trial Required) RFA-AG-23-034 Mechanism-Focused Research to Promote Adherence to Healthful Behaviors to Prevent Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD) and AD-Related Dementias (ADRD) (R61/R33 Clinical Trial Required) (Reissue of RFA-AG-22-016) RFA-AG-24-007 Roybal Centers for Translational Behavioral Research on Dementia Care, Caregiver Support, and Prevention of Alzheimer’s Disease and Related Dementias (AD/ADRD) (P30 Clinical Trial Required) (Reissue of RFA-AG-19-007) 8.B Achieved Increase investment in clinical trials that robustly test a variety of lifestyle interventions... DN 2012 AD Summit: 5B, 5C, 5D, and 5F 2017 Dementia Care Summit: 4.1, 5.1, 5.4 and 12.3 2018 AD Summit: 4L and 5H 2021 AD Summit: 6.G, 6.H and 6.I Blog: Setting goals to be more active slows memory decline in older African Americans News: Intensive blood-pressure control slowed white matter disease in adults age 75 and older Daily multivitamin may improve cognition in older adults Highlight: Hearing aids slow cognitive decline in people at high risk Highlight: Could 'musical medicine' influence healthy aging? Workshop: The Landscape of Early (Neuro)Psychological Changes in AD/ADRD Project Webinar Series Workshop: NASEM Research Priorities for Preventing and Treating Alzheimer’s Disease and Related Dementias Highlight: Online conversations show potential cognitive benefit for socially isolated older adults Highlight: Personalized health coaching may improve cognition and lower dementia risks in some older adults Highlight: Tai chi, especially an enhanced version, may improve cognition in older adults with memory problems Non-Pharmacological Interventions NIA Ongoing Alzheimer’s and Related Clinical Trials and Studies Preventing Alzheimer’s Disease with Cognitive Training: The PACT Trial Exercise in Adults with Mild Memory Problems (EXERT) MIND Diet Intervention to Prevent Alzheimer’s Disease Multidomain Alzheimer’s Risk Reduction Study (MARRS) Exercise and Intensive Vascular Risk Reduction in Preventing Dementia Modulation Effects of Baduanjin Mind-body Exercise on Subjective Cognitive Decline Multi-omic Investigation of Exercise Effects in Mild Cognitive Impairment Physical exercise and Blood-brain communication: exosomes, Klotho and choroid plexus US Pointer Ancillaries: Alzheimer’s Gut Microbiome Project US Pointer Ancillaries: US POINTER Neuroimaging Ancillary Study US Pointer Ancillaries: POINTER-ZZZ: Sleep Ancillary to U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk of Alzheimer’s Disease Neuro-exergaming for the prevention and remediation of decline due to Alzheimer's disease and related dementias: A clinical trial of the interactive Physical and Cognitive Exercise System (iPACES v3) Intermittent Hypoxia Training: A Novel Therapy for Mild Cognitive Impairment SynchronyGamma: A Music-Based Intervention for Alzheimer's and Mild Cognitive Impairment The Impact of Weight Loss on Alzheimer's Disease Risk in Adults with Down Syndrome The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study
- Initiate clinical trials for at least 3 non- pharmacological interventions aimed at Alzheimer's Disease (AD) and Alzheimer's Disease Related Dementias (ADRD) treatment and/or prevention. Ensure that the trials are designed to robustly test the therapeutic mechanism and to enable comprehensive success/failure analysis upon the trial completion.
- Incorporate digital health devices and/or deep multi-omic profiling in at least six (6) non-pharmacologic intervention studies to:
- Track adherence to treatment and treatment response;
- Understand mechanisms of action and person-specific trajectories of response;
- Identify optimal ways to integrate digital technologies and optimize the analysis and interpretation of the collected data.
- Support a systematic effort to provide evidence-based guidelines for the development of protocols for the design and delivery of non-pharmacologic interventions.
- Support research focused on identifying effective strategies to modify behavior to increase adherence and compliance in trials and best ways to support and maintain behavior modification and participant engagement across diverse populations, after the trial is complete.
- Employ engaged research models for stakeholder involvement as research partners, including centers and other research networks.
Summary of Key Accomplishments
A variety of lifestyle interventions for primary prevention or treatment of AD/ADRD are currently under study. The efficacy of some lifestyle modifications in slowing or preventing cognitive decline has been established in clinical trials. For example, investigators have demonstrated that intensive control of blood pressure may slow age-related brain damage and the occurrence of mild cognitive impairment, which can be a precursor of dementia.
As of August 2025, NIA is funding more than 150 early- and late-stage clinical trials focused on lifestyle and behavioral interventions, such as cognitive training, brain stimulation, and exercise. For example, a recent NIA-funded study found that tai chi, particularly an innovative form that combines mental puzzles and challenges with the traditional physical movements, improved cognition in older adults with mild cognitive impairment.
Several trials of risk reduction approaches reported out in 2024. One trial found that hearing aids reduced the rate of cognitive decline in older adults at high risk of dementia by almost 50% over a three-year period. Findings from another set of clinical trials suggest that a daily multivitamin modestly improves memory and cognition in older adults; and recent findings from a pilot study of personalized health coaching, aimed at addressing an individual’s specific dementia risk factors led to modest improvements in cognitive composite score, dementia risk factors, and quality of life compared with a health education control group. Additionally, regular, guided online conversations designed to stimulate brain regions associated with memory, executive function, and abstract thought showed potential for helping prevent cognitive decline among socially isolated older adults.
Because adherence to lifestyle modification is a challenge for many individuals, NIA supports the Roybal Center for Promoting Adherence to Behavior Change and Enhancing Cognitive Function. With a focus on physical activity as a strategy for preventing AD/ADRD, the Center is establishing clinical trials that support adherence to the intervention after the trial ends. Interventions will leverage wearable technology and integrate generative artificial intelligence with predictive modeling to deliver precision interventions.
The key accomplishments summary is current as of September 2025.