National Plan to Address Alzheimer's Disease: 2018 Update. Strategy 1.B: Expand Research Aimed at Preventing and Treating Alzheimer's Disease and Related Dementias

10/19/2018

HHS and its federal partners will expand clinical trials on pharmacologic and non-pharmacologic ways to prevent AD/ADRD and manage and treat its symptoms. The Federal Government will address the challenge of enrolling enough people in clinical trials who are representative of the country's population, including racial and ethnic populations that are at higher risk for AD/ADRD, through new partnerships and outreach. These actions will build on ongoing research focused on the identification of genetic, molecular and cellular targets for interventions and build on recent advances in the field.

(UPDATED) Action 1.B.1: Expand research to identify the molecular and cellular mechanisms underlying Alzheimer's disease and related dementias, and translate this information into potential targets for intervention

In the past year, NIA and NINDS have issued several funding opportunity announcements (FOAs) focused on research to help develop a better understanding of the growing list of genetic risk factors and molecular pathways that are involved in AD/ADRD. In response to these FOAs and investigator-initiated studies, researchers are developing a new generation of research tools to identify, explore, and validate a variety of targets with therapeutic potential. These sophisticated tools allow researchers to collect and integrate layers of biological data in novel ways -- opening the door to new insights into the origins and progression of AD/ADRD.

These new tools are also helping researchers gain a clearer picture of the complex underlying mechanisms of these devastating neurological disorders. They are leading to an understanding of the interplay among relevant molecules and systems, the relationship between amyloid and tau proteins, the role of immunity and inflammation, and the involvement of metabolic and cardiovascular pathways. This broader view of the basic biology of AD/ADRD could lead to potential breakthroughs.

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(UPDATED) Action 1.B.2: Expand genetic epidemiologic research to identify risk and protective factors for Alzheimer's disease and related dementias

Another key component in the growing toolkit of precision medicine for AD/ADRD is the Alzheimer's Disease Sequencing Project (ADSP), an international resource of genetics data from multiple centers and studies. Launched in 2012, the ADSP is designed to promote innovative collaboration among scientists to provide genetic samples for sequencing with the goal of identifying from multi-ethnic populations new genetic variants that influence risk and protection from AD/ADRD. In 2017, NIA launched the ADSP Follow-Up Study, which aims to pursue rare variants in a range of different populations, including those that have been underrepresented in sequencing studies.

Leveraging the existing infrastructure of the ADSP, the Follow-Up Study aims to generate whole-genome sequence data in African American, Hispanic, American Indian and Alaska Native, and Asian populations. In addition to the ADSP Follow-Up Study, NIA has several ongoing FOAs that call for research to enhance the ability to uncover the genetic underpinnings of AD/ADRD, furthering our understanding of rare risk and protective variants.

To improve our understanding of geographic and racial disparities in cardiovascular and cerebrovascular risk factors that lead to cognitive impairment and dementia, NIH is supporting the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and the Northern Manhattan Study (NOMAS) which are diverse longitudinal cohort studies of African American or Black, and Hispanic or Latino participants. As the emerging scientific consensus recognizes the role of midlife cardiovascular and cerebrovascular health in cognitive outcomes, the research focus of these two studies has recently been expanded to include investigation of health disparities in risk factors for dementia, and how they relate to stroke risk factors.

To advance further discovery for genetic factors and molecular pathways involved in FTD, NIH is also supporting the FTD Sequencing Consortium. This genetics consortium is composed of researchers at universities in the United States and at NIH who are utilizing whole genome sequence technology to generate sequence for 4,000 autopsy-confirmed and clinical characterized FTD cases.

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(UPDATED) Action 1.B.3: Increase enrollment in clinical trials and other clinical research through community, national, and international outreach

Since 2016, with facilitation by the Alzheimer's Association and in close collaboration with experts from government, private, and academic sectors, NIA has led an effort to develop comprehensive goals and strategies to enhance recruitment into clinical research, particularly focusing on underrepresented communities. To ensure broader input, in 2018 NIA gathered feedback on the recruitment strategies through the IdeaScale crowdsourcing platform. The culmination of these efforts will be the forthcoming National Strategy for Recruitment and Participation in Alzheimer's Disease Clinical Research.

NIA continues to promote participation in AD/ADRD clinical trials, studies, and registries through its Alzheimer's Disease Education and Referral (ADEAR) website portal; clinical trials listing and monthly e-alert to more than 50,000 subscribers; social media messages through Facebook and Twitter; infographics; presentations; and promotion of the Recruiting Older Adults into Research (ROAR) toolkit of customizable materials for aging services and public health professionals to use in community settings and social media in English, Spanish, and Chinese; and collaboration with Administration for Community Living (ACL), Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA) and the Patient-Centered Outcomes Research Institute (PCORI)-funded Alzheimer's and Dementia Patient/Caregiver-Powered Research Network to encourage research participation among older adults. NIA is also developing an online repository of planning tools, best practices, and materials to support researchers' recruitment and retention efforts.

Additionally in 2018, NIA released a new FOA -- Examining Diversity, Recruitment and Retention in Aging Research (PAR-18-749) -- to encourage building new, collaborative teams to target gaps in recruitment and retention methods and outcomes, as well as establishing the community infrastructure needed to accelerate studies.

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(UPDATED) Action 1.B.4: Monitor and identify strategies to increase enrollment of racial and ethnic minorities in Alzheimer's disease and related dementias studies

See 1.B.3 for updates regarding the National Strategy for Recruitment and Participation in Alzheimer's Disease Clinical Research that is currently under development. This strategy will include approaches to increase enrollment of racial and ethnic minorities in AD/ADRD studies. In April 2018, NIA released a new FOA -- Examining Diversity, Recruitment and Retention in Aging Research (PAR-18-749) -- to encourage building new, collaborative teams to target gaps in recruitment and retention methods and outcomes, as well as establishing the community infrastructure needed to accelerate recruitment.

Additionally, the National Institute on Minority Health and Health Disparities (NIMHD) has begun a new clinical trial on Addressing the Knowledge and Recruitment Gap in Alzheimer's Disease (AD) and Precision Medicine (PM) among Native People. An innovative pragmatic Randomized Controlled Trial, with 4,000 American Indian and Alaska Native enrollees as a part of the NIH All of Us program, with study will evaluate recruitment strategies for American Indians and Alaska Natives, create culturally tailored materials on AD-PM, evaluate the clarity and acceptability of the materials, and their effect on completion of the AD-PM Module and enrollment in the AD-PM Cohort, identify patient-level predictors of AD-PM cohort enrollment, and evaluate potential differences in the effectiveness of recruitment approach by age, sex, education, cultural identity, and rurality.

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(UPDATED) Action 1.B.5: Conduct clinical trials on the most promising pharmacologic interventions

Launched in 2017, a new clinical trials consortium funded by NIA is expected to accelerate and expand studies for therapies in AD/ADRD. The new NIA-funded Alzheimer's Clinical Trials Consortium (ACTC) will develop and implement cutting-edge participant recruitment and retention strategies, especially in diverse populations and establish a new minority outreach and recruitment team. ACTC is a "next-generation" infrastructure designed to harness best practices and latest methods for Alzheimer's trials.

The ACTC's design allows rapid start-up of clinical trials and provides infrastructure and support in areas such as imaging, biostatistics, data management, and recruitment. It also requires and supports sharing of data and biosamples. With the current funding announcement, NIH anticipates applications to develop and implement Phase I to Phase III clinical trials that would use ACTC coordination and management for promising pharmacological and non-pharmacological interventions.

In addition to the ACTC infrastructure, NIH currently sponsors approximately 140 active trials of interventions to enhance cognitive health in older adults and to prevent, treat, or manage AD/ADRD. NIH also released several FOAs specifically focused on clinical trials for AD/ADRD. These include pharmacologic as well as lifestyle interventions.

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(UPDATED) Action 1.B.6: Continue clinical trials on the most promising lifestyle interventions

See 1.B.5 for updates regarding the ACTC and ongoing clinical trials supported by NIA. Many of the approximately 140 active trials of interventions to enhance cognitive health in older adults and to prevent, treat, or manage AD/ADRD include testing lifestyle interventions such as diet and exercise. NIA has also released several FOAs specifically focused on clinical trials for AD/ADRD.

For more information, see:

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(NEW) Action 1.B.7: Expand research focused on needs related to the intersection of Down syndrome and Alzheimer's disease and related dementias

The FY 2018 omnibus appropriations report provided NIH with the opportunity to not only expand its current efforts on Down syndrome and AD/ADRD, but to build an integrated effort across NIH that will be truly transformative in this area and other commonly co-occurring conditions in individuals with Down syndrome. The INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) project was launched in June 2018 in support of a congressional directive. INCLUDE will focus on three overall goals: (1) conducting targeted, high-risk, high-reward basic science studies on chromosome 21; (2) assembling a large study population of individuals with Down syndrome; and (3) including individuals with Down syndrome in existing clinical trials.

NIA and NICHD have been funding an Alzheimer's Biomarker Consortium -- Down Syndrome since 2015, which aims to identify biomarkers that indicate AD is developing or progressing and track the AD process in people with Down syndrome. NIA is also funding a Phase I clinical trial to investigate the safety and tolerability of an immunotherapy vaccine for treatment of AD in adults with Down syndrome.

NIA and NICHD have also collaborated to produce and disseminate information for people with Down syndrome and their families regarding the interplay of Down syndrome and dementia, and the importance of participating in research. Efforts include a fact sheet, "Alzheimer's Disease in People with Down Syndrome", and outreach via email and social media.

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