Focus on Alzheimer's Disease and Related Dementias

Focus on Alzheimer's Disease and Related Dementias

Sketch of brain being erased

NINDS Program Description

What is AD/ADRD?

Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) refers to the most common forms of dementia. Dementia likely affects more than 5 million people in the U.S. and more than 47 million people worldwide. At this time, there are no known treatments to prevent or stop the progression of dementia. The toll on individuals, caregivers and society is enormous and will only increase as the population ages unless effective interventions are developed. NINDS collaborates with NIH’s National Institute on Aging (NIA), the lead NIH Institute for Alzheimer’s disease (AD) research, to establish research priorities and fund biomedical research in AD as well as several Alzheimer’s disease-related dementias (ADRDs).

While AD is the most common dementia diagnosis, ADRDs share many cognitive and pathological features with and can be difficult to distinguish from AD. In fact, more often than not, patients with a diagnosis of Alzheimer’s disease present with different mixtures of brain pathologies, complicating both the diagnosis, as well as the treatment.

The ADRDs include:

Going forward, NINDS and NIA will continue to partner in AD/ADRD research planning and implementation, and we urge the research community to join in our efforts to accelerate scientific progress toward reducing the enormous burden and cost of dementia.

FOA Concepts Planned for Fiscal Year 2022

We are excited to share with you that NINDS Council recently cleared research concepts for potential future funding opportunity announcements. Please take note and start thinking about what your plans to apply.

It is important to note that a cleared concept doesn’t definitively mean that an award mechanism or funding allocation is imminent or even going to happen. Nothing is official until FOAs are published in the NIH Guide.

Biomarkers for the Lewy Body Dementias RFA-NS-22-001. The purpose of this funding opportunity announcement (FOA) is to support hypothesis-driven clinical research applications that are focused on discovering novel diagnostic, prognostic, and/or therapeutic biomarkers for the Lewy Body Dementias (LBD). Biomarker research must be conducted in patients with LBD, must follow Parkinson's Disease Biomarker Program (PDBP) protocols for clinical assessment and biospecimen collection, and must be broadly shareable through the PDBP repositories. Submission deadline is October 22, 2021.

Clinical and Biological Measures of TBI-related Dementia Including Chronic Traumatic Encephalopathy (R01 Clinical Trial Not Allowed) PAR-22-024. Investigation of biological and clinical measures of TBI-related and CTE-related progressive neurodegeneration and neurocognitive decline associated with increased risk for dementia. Submission deadline is November 10, 2021.

Detecting Cognitive Impairment, Including Dementia, in Primary Care and Other Everyday Clinical Settings for the General Public and Health Equity, Pragmatic Clinical Trials (U01 Clinical Trial Required) RFA-NS-22-009. The purpose of this funding opportunity announcement (FOA) is to invite pragmatic clinical trial applications to test paradigms designed to address the unmet need to detect cognitive impairment, including dementia, in large and diverse populations seen in primary care across the United States when a patient, relative, or care provider indicates concern. Submission deadline is November 10, 2021.

NINDS Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed) PAR-22-022. The purpose of this program is to support a cohort of new and talented, independent investigators from diverse backgrounds (e.g. see NOT-OD-20-031) conducting AD/ADRD research.

NINDS Institutional AD/ADRD Research Training Program - provide support for institutional research training programs in AD/ADRD.

Role of Astrocytes in Degeneration of the Neurovascular Unit - encourage the field to propose basic disease-related research to address basic research on the mechanisms of reactive astrogliosis in degeneration of the neurovascular unit that contributes to cognitive impairment and dementia.

Prodromal Synaptic and Circuit Changes that Contribute to AD/ADRD Onset and Progression - develop and use models to investigate the contribution of synaptic activity and circuit plasticity changes to the progression of disease processes that underlie neurodegeneration in dementia.

Longitudinal Single Cell Characterization of ADRD Postmortem Tissue (R01 Clinical Trial Not Allowed) PAR-22-029. The purpose of this funding opportunity is to support projects to identify cellular changes in ADRD post-mortem brain tissue across disease progression.

Multi-Disciplinary Collaborations to Understand Mechanisms of Systemic Immune Signaling and Inflammation in ADRD and its Progression (R01 Clinical Trial Not Allowed) PAR-22-023. Recent findings have raised the hypothesis that systemic immune responses could play direct or indirect roles in brain neurodegeneration leading to AD/ADRD and have been significantly less studied than immune responses confined exclusively to within the brain parenchyma. The purpose of this funding opportunity announcement (FOA) is to support partnerships and new collaborations between neuroscientists and immunologists to expand the research base in this area with the long-term goal of bringing more immunology expertise into the AD/ADRD field and to support further work in this area through investigator-initiated and other mechanisms. Submission deadline is October 22, 2021.

Leveraging Existing Data Resources for Computational Model and Tool Development to Discover Novel Candidate Mechanisms and Biomarkers for ADRD (R01 Clinical Trial Not Allowed) RFA-NS-22-006. The purpose of this funding opportunity announcement is to expand the use of existing ADRD data resources to drive, via computational model development and dissemination, new discoveries that can lead to better understanding of mechanisms, clinical risk assessment and outcomes, and to identify novel candidate biomarkers for ADRD. Submission deadline is October 26, 2021.

Clinical Relevance of the Linkage between Environmental Toxicant Exposures and Alzheimer’s Disease and Related Dementias - conduct mechanistic AD/ADRD research on the actions of neurotoxicants on the nervous system. See NOT-NS-22-004 for more information.

Selectively Target Technology Development to Understand How Changes or Dysfunction at the Capillary, Arterioles, and Small Lymphatic Vessels Level Can Have Long-term Impact on AD/ADRD (R01 Clinical Trial Not Allowed) PAR-22-026. The purpose of this Funding Opportunity Announcement (FOA) is to solicit studies that will advance the mechanistic understanding of small vessel vascular contributions to cognitive impairment and dementia (VCID) through the development of new technologies and innovative methods that enable the imaging and/or functional assessment of the small blood and lymphatic vessels and perivascular spaces of the brain.Submission deadline is November 8, 2021.

Postmortem Pathology, Cellular, and Molecular Analyses to Determine the Significance of White Matter Lesions and other Imaging Findings of Presumed Vascular Origin During Life - understand the pathogenic processes associated with the varied brain lesions of presumed vascular origin seen on MR imaging during life of both healthy elderly individuals and patients who exhibit symptoms consistent with AD/ADRD.

Adding TBI Assessments to AD/ADRD Cohorts NOT-NS-22-022. These administrative supplements will provide funding to existing NINDS-funded AD/ADRD relevant cohort studies to support the inclusion/addition of NINDS Common Data Elements (CDEs) for life-time exposure to TBI (Ohio State University TBI Identification Form), other FITBIR CDE for life-time TBI exposure measures (e.g. FITBIR Injury History Form) or Brain Injury Screening Questionnaire (BISQ), and other relevant TBI-related NINDS CDEs to current clinical assessment batteries. Data will be available to better understand the prevalence of TBI history in these populations and could be hypothesis generating for studying the pathophysiology underlying TBI as a risk factor for AD/ADRDs. Submission deadline is November 15, 2021.

 

AD/ADRD - At-A-Glance

  • AD affects more than 5 million people in the U.S.
  • FTD is the leading cause of dementia in people under age 60
  • LBD affects more than 1 million Americans and slightly more men than women
  • Cerebrovascular disease often co-occurs with AD
  • Reducing vascular risk factors may reduce risk for dementia
  • The majority of all dementia cases (age 65+) are mixed dementias, mainly Alzheimer’s pathology mixed with cerebrovascular disease and/or Lewy bodies
  • No known treatments prevent AD/ADRD onset or progression

Extended Payline for AD/ADRD Investigator-initiated Research

Since FY2016, the NIA has utilized a higher pay line for AD/ADRD research to support investigator-initiated research grants, which it extends to NINDS for applications that meet this bar. This pay line is considerably higher than the pay line for other types of research in either NINDS or NIA. NINDS remains very interested in grant submissions focused on innovative ideas that could lead to prevention or effective treatment of AD/ADRD.

NIH Estimates of Funding for Various Research, Condition, and Disease Categories

Research/Disease Areas* FY 2016
(Actual)
FY 2017
(Actual)
FY 2018
(Actual)
FY 2019
(Actual)
FY 2020
(Actual)
Alzheimer's Disease Including
Alzheimer's Disease Related
Dementias (AD/ADRD)
$986 $1,423 $1,911 $2,398 $2,869
Alzheimer's Disease $929 $1,361 $1,789 $2,240 $2,683
Frontotemporal Dementia $65 $91 $94 $158 $166
Lewy Body Dementia $22 $31 $38 $66 $84

*Dollars in millions and rounded

Proceedings & Outcomes

ADRD 2019 summit poster

AD/ADRD Summits

The National Plan’s Goal 1 aims to prevent and effectively treat (delay onset, slow progression of) AD/ADRD by 2025. To help achieve Goal 1, and as a federal action specified in the National Plan, periodic summits are held to set and refine AD/ADRD research priorities in the National Plan. Visit the Assistant Secretary for Planning and Evaluation (ASPE) to learn more about the National Plan to Address Alzheimer’s disease.

Alzheimer's Disease-Related Dementias Summit 2019

Alzheimer's Research Summit 2018

Alzheimer's Disease-Related Dementias Summit 2016; Proceedings article summarizing the 2016 Alzheimer's Disease-Related Dementias Summit

Alzheimer's Disease Research Summit 2015

Alzheimer's Disease-Related Dementias Summit Conference 2013; Proceedings article summarizing the 2013 Alzheimer's Disease-Related Dementias Conference

Resources and Tools

Research priorities for ADRD are identified and updated through periodic NIH-hosted ADRD Summits.

IADRP reports categories of funded research supported by public and private organizations both in the US and abroad all categorized using the Common Alzheimer's and Related Dementias Research Ontology (CADRO)

A national database of standardized clinical and neuropathological research data (NIA/NIH). The standardized data and neuropathology data are collected at the NIA funded Alzheimer’s Disease Centers.

Tool for tracking funding initiatives and activities aimed at achieving the Research Milestones that were developed from NIH-hosted AD and ADRD Summits. 

NCRAD is an NIA funded biorepository for Alzheimer’s Disease and Related Dementias studies.  NCRAD banks a variety of biospecimens including DNA, RNA, plasma, serum, CSF, LCLs, and PBMCs

Available cell sources currently include fibroblasts and/or induced pluripotent stem (iPS) cells.

BioSEND currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva from 16 different biomarker studies that focus on neurological and neuropsychiatric diseases.

Housing over  DNA samples and cell lines.

AlzPED serves as a knowledge platform for the dissemination of data and analysis in a manner that promotes efficiency, transparency, reproducibility and accuracy of research aimed at preclinical therapy development for AD.

The PDBP facilitates biomarker discovery and validation efforts, leveraging broadly shared clinical and biospecimen data, with the overarching goal of improving clinical trial design and therapeutic development in PD, Lewy Body Dementia (LBD), and Parkinsonisms.

Since 2013, the NIH NeuroBioBank has catalyzed scientific discovery through the centralization of resources aimed at the collection and distribution of human post-mortem brain tissue.

We will create a foundational repository of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR/Cas9-based genetic engineering. Our target goals are 132 variants across 72 AD/ADRD genes, 8 of which are known AD-related genes, 15 are genes linked to Dementia with Lewy Bodies/Parkinson’s Disease, 28 genes are associated with Frontotemporal Dementia/Amyotrophic Lateral Sclerosis, and 21 are genes associated with other neurodegenerative disorders.