Clinical Interventions and Diagnostics Portfolio

Supporting the development of novel treatments and diagnostics for Alzheimer's Disease and Related Dementias (AD/ADRD)

The Clinical Interventions and Diagnostics Branch spearheads diverse programs focused on bringing novel therapies and diagnostics for Alzheimer's disease and related dementias to the clinic.

Background

Spurred by the growing threat of Alzheimer’s disease (AD) and AD-related dementias (ADRD) to our loved ones, families, and the health and economic systems, the National Plan to Address Alzheimer’s Disease , an initiative in place since 2012, drives our efforts to find treatments to delay or prevent AD and ADRDs by 2025. Lawmakers have supported that mission with major increases in funding for research toward treatment and prevention. Developed in parallel with this increased congressional support, the AD+ADRD Research Implementation Milestones represent a research framework detailing specific steps and success criteria towards achieving the goals outlined in the National Plan to Address Alzheimer's Disease . The scientific community is galvanized. We are tackling Alzheimer’s and related dementias on an unprecedented scale, moving forward with innovative approaches and new discoveries that will need to be tested as expeditiously and comprehensively as possible. The Clinical Interventions and Diagnostics Branch of the NIA’s Division of Neuroscience is spearheading many of these programs and studies. Please browse our page to learn more about the NIA/NIH supported programs and projects that are moving us closer to treatments and cures for AD and ADRD.

Clinical Interventions

Clinical Trials

NIA’s portfolio of AD/ADRD prevention and intervention trials is diverse with respect to drug and mechanistic targets, as well as the stages of AD/ADRD that are addressed. Our active trials include: early-stage clinical drug development , late-stage clinical drug development , non-pharmacological interventions , clinical therapy development for neuropsychiatric symptoms of dementia, and care and caregiver interventions . Please visit the NIA-Funded Active Alzheimer’s and Related Dementias Clinical Trials and Studies webpage compiles more details about the trials in our portfolio.

The NIA invites applications that propose to develop and implement early-stage and late-stage clinical trials of promising pharmacological and non-pharmacological interventions to treat individuals with age-related cognitive decline and in individuals with Alzheimer's Disease (AD) across the spectrum from pre-symptomatic to more severe stages of disease, and to stimulate studies to enhance trial design and methods.

The Clinical Interventions and Diagnostics Branch also manages many clinical trial infrastructure programs that utilize diverse approaches to target AD/ADRD. Some of these key programs are highlighted below.

Alzheimer's Clinical Trials Consortium (ACTC)

Launched in December 2017, the ACTC is a clinical trials infrastructure designed to accelerate and expand studies for therapies in Alzheimer's disease and related dementias by maintaining a clinical trial ready cohort. ACTC's mission is to provide an optimal infrastructure, utilizing centralized resources and shared expertise, to accelerate the development of effective interventions for Alzheimer’s disease and related disorders.

Dominantly Inherited Alzheimer Network (DIAN)

DIAN is an international research effort focused on dominantly inherited AD, which is a rare form of Alzheimer's that causes memory loss and dementia in individuals -- which typically occurs during individual's 30s to 50s. The disease affects less than 1% of the total population of people with AD. The aim of DIAN is to find solutions to treat or prevent this disease and, potentially, all forms of AD.

Dominantly Inherited Alzheimer Network - Trial Unit (DIAN-TU)

The DIAN-TU , the clinical research arm of DIAN, is an international partnership dedicated to designing and managing interventional therapeutic trials for individuals with and at risk of DIAD. The DIAN-TU’s primary goal is to implement effective, safe and efficient clinical trials that have the highest likelihood of success in advancing overall treatments as well as scientific understanding of inherited Alzheimer's disease. In addition, research within the DIAN-TU is likely to advance broader understanding the spectrum of Alzheimer's disease with regards to causes, early detection/diagnosis, the effects of multiple classes of drugs and the impact of treating Alzheimer's disease early.

Alzheimer's Biomarkers Consortium - Down Syndrome (ABC-DS)

The ABC-DS project is a large research initiative to find biomarkers to track AD in people with Down syndrome. Over a five-year period, researchers will collect information and blood samples from people with Down syndrome and their siblings. Participants may undergo physical exams, neurological tests, brain scans, and assessments to measure cognition, memory, and movement. Additional information will be obtained through personal and family health history, caregiver questionnaires, and genetic studies. Information gained from this initiative may help individuals with Alzheimer's and Down syndrome, as well as individuals with only Alzheimer's disease.

Clinical Trial Design and Innovation Programs

The NIA/NIH is committed to the development of Clinical trial designs that promote and enrich standard practices for defining clinically significant outcomes that treat AD/ADRD. An outline of our goals can be found in the Clinical Trial Innovation section of the AD+ADRD Research Implementation Milestones .

Key clinical trial design and innovation programs are highlighted below.

NIA IMPACT Collaboratory : The National Institute on Aging (NIA) Imbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory works to build the nation's capacity to conduct pragmatic clinical trials of interventions embedded within health care systems for people living with dementia and their caregivers.

Trial Innovation Network : Innovation Centers focused on operational excellence, operational innovation, and quality by design. The TICs are charged with coordinating and providing innovative, high quality operational support for clinical trials.

Clinical Interventions team:

Biomarkers

Biomarkers for Dementia Detection and Research

Many types of biomarker tests are used for research on Alzheimer's disease and related dementias. Changes in the brains of people with these disorders may begin many years before memory loss or other symptoms appear. Researchers use biomarkers to help detect these brain changes in people, who may or may not have obvious changes in memory or thinking. Finding these changes early in the disease process helps identify people who are at the greatest risk of Alzheimer's or another dementia and may help determine which people might benefit most from a particular treatment.

The Diagnosis and Biomarkers Program in our branch covers a broad range of research related to clinical characterization of Alzheimer’s Disease and Related Dementias (ADRD). The science is broad: from genetics to neuroimaging, biochemistry, to machine learning. While some projects include animal or in vitro studies, most research is clinically focused, involving data or samples from human participants. While healthy controls may be studied, characterizing normal aging is not a primary goal. The Program has two complementary foci: understanding the underlying clinical biology of AD/ADRD, and developing tools (biomarkers) for use in clinical AD/ADRD research.

The Program supports a variety of NIH research grant mechanisms including research projects (R03, R21, R01), program projects (P01), and cooperative research agreements (U01, U19). The program also includes small business innovative research (SBIR R41/R43, R44) The Program does not include treatment research, Centers (P30, P50), research resources (R24, U24), or training (K, F, T). Studies of epidemiology and neuropathology or genetics are in the Epidemiology and Genetics Branch.

Examples of research topics include:

  • Development of biofluid (e.g., plasma and CSF) assays
  • Development of PET radioligands, & implementation in clinical cohorts
  • Studying novel MRI (& MRS) sequences in patients and animal models
  • MEG and EEG studies
  • Use of artificial intelligence and machine learning to predict and/or characterize disease progression
  • Application of new technologies in clinical research of early diagnosis and monitoring (e.g., digital biomarkers)

The Program supports several large, longitudinal AD/ADRD cohorts, including

Biomarkers and Diagnostics Program Contacts:

Technology

Older Americans are becoming increasingly tech-savvy, with more than 75 percent using smart phones and wearable devices. As older adults become more comfortable with these and other “smart” tech items like watches and fitness trackers, NIA-supported researchers are working to find innovative ways these devices can monitor and improve physical and cognitive health. We especially hope these efforts will foster earlier detection of cognitive change and improve capabilities for diagnosis and monitoring of AD/ADRD. Please check out our BLOG for information from an NIA workshop focused on the

.

Are you interested in health innovations using smart sensors and related technologies for AD and ADRD? NIA encourages all interested applicants, whether from academia, industry or a small business aimed at product development and commercialization, to contact a Program Director for more information on available funding opportunities.

Training and Technology Program Contact:

Alzheimer's Disease Research Centers

For Patients and Family Members:

Alzheimer’s Disease Research Centers

Since 1984, the National Institute on Aging has supported the Congressionally directed Alzheimer's Disease Research Centers (ADRCs) Centers of Excellence across the United States. The ADRCs provide infrastructure to most of the major NIA funded initiatives and provide resources (like biosamples and data) to researchers at their local institutions and across the country. Researchers at these Centers are working to translate research advances into improved diagnosis and care for people with Alzheimer's disease, as well as working to find a treatment or way to prevent Alzheimer's and other types of dementia. The ADRC’s offer individuals and families affected by Alzheimer's disease and other dementias a number of resources including help obtaining a diagnosis, appropriate medical management information, opportunities to volunteer and participate in clinical trials and other research, support groups and/or other special programs, and also autopsy . Importantly, ADRCs are spread across the country have community outreach to different local populations, to help us understand how dementia occurs in everyone, and they all also need volunteers without dementias to compare findings. Click here to find an ADRC near you !

Alzheimer’s Disease and Related Clinical Trials

Search for clinical trials and studies related to Alzheimer's, other dementias, mild cognitive impairment, and caregiving, as well as a list of featured studies in progress.

Alzheimer’s Disease Research Centers Team:

Recruitment and Retention

The National Institute on Aging of the NIH continues to emphasize the need for careful consideration of recruitment in Alzheimer’s and related dementias studies, to support and disseminate research on effective strategies for study participation, and to conduct further and targeted outreach and information to increase awareness. Specifically, there is a pressing need for increased and diverse participation in research studies as scientific opportunities emerge. Additional studies on new approaches will require greater numbers of people from across the disease spectrum, including healthy and preclinical individuals, and must ensure representation from racial, ethnic, and socioeconomic groups who may be differentially affected by dementia. We will continue to take a leadership role in implementation of the

working with all of you as we follow the guideposts provided therein.

Recruitment in -Action-

Outreach, Recruitment and Engagement (ORE) Cores of the Alzheimer’s Disease Research Centers

The National Institute on Aging funds Alzheimer's Disease Research Centers (ADRCs) at major medical institutions across the United States. Researchers at these Centers are working to translate research advances into improved diagnosis and care for people with Alzheimer's disease, as well as working to find a treatment or way to prevent Alzheimer's and other types of dementia.

Each of the ADRCs has an ORE core. As the name implies, they are responsible for:

  • community outreach regarding Alzheimer's Disease and other types of dementia
  • recruiting participants to research studies, not only those funded through the ADRC, but other affiliated studies as well as national research like ADNI, DIAN and clinical trials
  • engaging local communities including working with community advisory boards and community resources such as Area Agencies on Aging and non-governmental organizations.

The ORE Cores develop outreach and informational materials and share those materials through social media, local outlets and through NIA's ADORE (Alzheimer's and Dementia Outreach, Recruitment, and Engagement Resources). Recruitment efforts differ at each individual center, focusing on local research areas of focus and on local community demographics.

Resources: NIA Based

Alzheimer's & Dementia Outreach, Recruitment & Engagement Resources (ADORE )

ADORE is the NIA repository of resources to support the recruitment and retention of participants into clinical trials and studies on AD and ADRD.

Alzheimer's and related Dementias Education and Referral Center (ADEAR)

The ADEAR Center strives to be a current, comprehensive, unbiased source of information about Alzheimer's disease and related dementias. All our information and materials about the search for causes, treatment, cures, and better diagnostic tools are carefully researched and thoroughly reviewed by NIA scientists and health communicators for accuracy and integrity.

Alzheimer’s Disease and Related Dementias Clinical Studies Recruitment Planning Guide

This NIA guide for investigators, study coordinators, recruitment communications staff, and others involved in clinical research outlines strategies for improving community-based research participation.

ROAR

The NIA, Centers for Disease Control and Prevention (CDC), and the Administration for Community Living (ACL) are collaborating on the Recruiting Older Adults into Research (ROAR) project to encourage older adults and their family caregivers, including underrepresented populations, to consider participating in research. We are starting with a focus on Alzheimer’s and dementia research. Here , you can find a toolkit of easy-to-use, customizable materials that feature information on why research is important to healthy aging, what volunteers need to know about research studies, how older adults can make a difference by participating, and easy steps to take.

Health Disparities Framework

The NIA Health Disparities Research Framework showcases priorities and investments in this important aging research area. This page is designed to serve as a resource for scientists interested in investigating health disparities related to aging.

Recruitment Innovation Center

The Recruitment Innovation Center is focused on becoming a successful, evidence-based Center in recruitment and retention strategies in order to improve both the quality of future clinical trials and to raise awareness of the value of research thereby increasing trial enrollment and health outcomes across America.

Recruitment and Retention Program Contact:

Training, Career Development, and Education

NIA supports a variety of training and career development opportunities for individual pre-doctoral students and postdoctoral fellows , early-career investigators and clinician-researchers, and diversity of research workforce . We are committed to training the next generation of diverse researchers and investigators to conduct innovative and interdisciplinary research focused on AD and ADRD. These well-trained future leaders in the AD/ADRD field are a key component of NIA’s mission to accelerate the development of novel diagnostic tools and therapeutics that will help prevent or delay the progression of AD. Accordingly, NIA encourages students and early-stage researchers to pursue research careers in neurosciences, Alzheimer's disease and healthy brain aging. NIA also supports Institutional training program to Advance Translational Research on Alzheimer's Disease (AD) and AD-Related Dementias (T32, PAR-21-112 ).

For information on all training opportunities and grant mechanisms from NIA, visit here .

Please also review research program priority areas for training and career development by visiting our grants and funding pages , from the Division of Extramural Activities .

Training and Career Development Program Contact:

Clinical Trials Education Program Contacts:

Resources for Clinical Research Investigators

NIA guidance for the development and conduct of clinical trials, the sharing of data from NIA funded studies, and NIA funded infrastructure programs that help streamline these efforts are compiled below.

Tools for prospective and ongoing Clinical Trials:

Clinical Research Study Investigators Toolbox

The purpose of the NIA Clinical Research Toolbox is to provide a Web-based informational repository for investigators and staff involved in clinical research. The Toolbox contains templates, sample forms, guidelines, regulations, and informational materials to assist investigators in the development and conduct of high-quality clinical research studies relevant to the following topics:

DSMB responsibilities and requirements:

Ensuring the safety of participants enrolled in NIA-funded clinical trials is the highest NIA priority. This goal applies to any trial regardless of a study's phase, stage, size or intervention type. Guidance on the development of a Data Safety and Monitoring Plan (DSMP) and the role and responsibilities of the Safety Officer/DSMB is compiled in the NIA Guidance on Clinical Trials .

Data and Resource Sharing

Data sharing is essential for expedited translation of research results into knowledge, products, and procedures to improve human health. The NIA expects and supports the timely release and sharing of final research data to serve these and other important scientific goals. We recently published a series of blogs that summarize 1) open science translational research programs , 2) new requirements for data and biosample sharing from AD/ADRD clinical trials and 3) Data management and sharing requirements (link will be added soon.) Additional guidance and resources relevant to data sharing principles and practices for NIA funded grants can be found on the NIA Guidance on Data Sharing and the Data Sharing Resources for Researchers webpages.

Data and Resource sharing plans

Currently, NIH policy requires an agreed data-sharing/resource-sharing plan for awards of $500k and over. The policy allows flexibility below the 500k threshold for individual Notices of Funding Opportunity (NOFOs). Many of NIA’s currently open NOFOs require data-sharing or resource-sharing plans as a component of the application regardless of the requested budget. Data Sharing plans should include 5 core elements:

  1. The name of the repository/consortium/enclave where the data or other resource will be stored, or a clear plan and demonstrated capacity for the Investigator to share from their own site(s).
  2. A description and justification of the timetable to release the data and/or other resource(s). Some NOFOs, including the early-stage clinical trial NOFO PAR18-877 and the late- stage clinical trial NOFO PAR18-878, have specific timeframes regarding when data and bio-samples generated by the study should be publicly available. Refer to the Notice of Funding Opportunity or contact your Program Officer for clarification regarding these timelines.
  3. A description of any restrictions on sharing (beyond temporal restrictions) and a legitimate justification.
  4. For studies involving human participants, the Data sharing plan should outline how disseminated data will be deidentified and secured.
  5. A description of how the data and/or other resource(s) will be curated to allow easy access to qualified users.

NIA-funded Resources for the AD/ADRD Scientific Community

Accelerating Medicines Partnership- Alzheimer’s Disease (AMP- AD)

The Accelerating Medicines Partnership-Alzheimer's Disease (AMP-AD) Biomarkers Project is a consortium of two NIA-supported Phase II/III secondary prevention trials ( listed here ) testing several anti-amyloid therapies. Through the AMP-AD partnership, imaging and fluid biomarker panels already included in these trials will be supplemented with tau PET imaging and novel fluid biomarkers.

ACTC

The Alzheimer's Clinical Trials Consortium (ACTC) is a clinical trials infrastructure launched in December, 2017 and designed to accelerate and expand studies for therapies in Alzheimer's disease and related dementias. ACTC's mission is to provide an optimal infrastructure, utilizing centralized resources and shared expertise, to accelerate the development of effective interventions for Alzheimer’s disease and related disorders.

Alzheimer’s Disease Neuroimaging Initiative

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a longitudinal multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer’s disease (AD). Since its launch more than a decade ago, the landmark public-private partnership has made major contributions to AD research, enabling the sharing of data between researchers around the world.

LONI Image and DATA Archive

The Image & Data Archive (IDA) provides tools and resources for de-identifying, integrating, searching, visualizing, and sharing a diverse range of neuroscience data, helping facilitate collaborations between scientists worldwide. The IDA contains data collected for more than 80 studies focused on processes such as development, aging and the progression of specific diseases including AD and ADRD. Many studies have generous data sharing policies and support online access requests. The Featured Studies section of this page provides more details.

National Centralized Repository for Alzheimer’s Disease and Related Dementias

The goal of the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) is to support research focused on the etiology, early detection and therapeutic development for Alzheimer disease and related dementias. NCRAD is a national resource where clinical information and biological materials, such as DNA, plasma, serum, RNA, CSF, cell lines and brain tissue can be stored and requested. NCRAD currently maintains samples from individuals with Alzheimer’s disease and/or related dementias as well as healthy controls.

Notices of Funding Opportunity

NIA is actively soliciting applications for studies that will further our mission. Open Notices of Funding Opportunity (NOFOs) relevant to our work in the Clinical Interventions and Diagnostics Branch are listed below.

Clinical Trials

Drug Repurposing and Combination Therapies