NAPA at 10: A decade of Alzheimer’s and related dementias research progress
As we mark the 10-year anniversary of the National Plan to Address Alzheimer’s Disease, which arose from the National Alzheimer's Project Act (NAPA), it’s striking to pause for a moment and consider how far we have come. Thanks to increased congressional funding, NIH spending on Alzheimer’s and related dementias research advanced nearly 4.5-fold between fiscal years 2015 and 2020, reaching $2.87 billion. This momentum has enabled NIA-funded science to take significant strides forward.
Some of the many major accomplishments that the NAPA has made possible include:
Illuminating genetics: Ten years ago, we knew of just 10 genes associated with Alzheimer’s disease, and 20 years ago, we knew of only four. Today, researchers have identified more than 70 associated genetic areas, opening multiple new foci for potential prevention and treatments.
Improving Alzheimer’s disease models: It is extraordinarily difficult to mimic the brain’s complexity in standard lab models. Improving these models will help us better understand brain-related diseases and test existing and novel drugs as potential therapies. Thanks to NIH research, we now have the “Alzheimer’s in a dish” model, the first to contain the amyloid and tau hallmarks of the disease. In recent years, scientists built two additional “disease-in-a-dish” models and have developed more than 50 new mouse models including one that produces a form of the human beta-amyloid protein.
Expanding biomarkers: Before biomarker tests were developed in the early 2000s, the only sure way to know whether a person had Alzheimer’s was via autopsy. Researchers can now use brain imaging methods or lab tests to diagnose people living with the disease. NIA-funded scientists continue to explore novel blood biomarkers for various forms of amyloid, tau, and other promising targets. As one result, NIA small business innovation research funding helped validate and commercialize the PrecivityAD™ test, a more affordable and less invasive alternative to traditional Alzheimer’s tests like spinal taps or brain scans. This blood biomarker-based test is now widely available to doctors and researchers across the United States.
Identifying novel drug targets and therapies: The Accelerating Medicines Partnership® Program for Alzheimer’s Disease has aided discovery of more than 550 novel candidate therapeutic targets and is now exploring a precision medicine approach to therapy development. In a parallel effort, the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study, investigators found that use of certain rheumatoid arthritis drugs is associated with a lower incidence of Alzheimer’s and related dementias in people with cardiovascular disease.
Increasing clinical trials, targets, recruitment, and retention: Today, NIA supports more than 400 clinical trials for Alzheimer’s and related dementias, compared to just 38 in 2015. These prevention and intervention trials reflect diverse drug and mechanistic targets, across different stages of disease. To enhance clinical trial diversity, recruitment, and retention, NIA developed the National Strategy for Recruitment and Participation in Alzheimer’s and Related Dementias Clinical Research and continues to invest in initiatives like the Alzheimer’s and Dementia Outreach, Recruitment, and Engagement repository. To enhance diversity in clinical trials, NIA developed the Clinical Research Operations and Management System (CROMS), which will provide real-time tracking of clinical trial enrollment and retention data. Our institution also launched OutreachPro, which enables researchers to create tailored and tested clinical trial recruitment materials to better reach underrepresented populations.
Paving the way for prevention: Scientists are learning more about risk factors and potential lifestyle changes that may help prevent dementia. In 2019, a randomized clinical trial showed that intensive high blood pressure control may significantly reduce the buildup of brain white matter lesions and the occurrence of mild cognitive impairment. In addition, a 2020 study found that individuals who made multiple healthy lifestyle choices may have a much lower risk for Alzheimer’s.
Building research infrastructure: Targeted strategic investments are helping to expand the research infrastructure for Alzheimer’s and related dementias including the Alzheimer’s Clinical Trials Consortium, the NIA Impact Collaboratory, and the NIH Intramural Center for Alzheimer’s and Related Dementias (CARD), which launched in 2020. These initiatives will expand studies for therapies, enhance recruitment of underrepresented participants, spur innovation around complex care management, and boost basic, translational, and clinical research.
As we take stock of this remarkable decade of discovery, we are inspired by the scientists, clinical trial participants, caregivers, and many other stakeholders whose hard work and dedication are helping to tackle this devastating disease. We hope you will join us as we continue moving forward! To kick things off, we invite you to watch our video series featuring stories of progress from the field, join us online June 15 for the #AlzScience Twitter Chat to discuss this exciting momentum, or share your perspective in a comment below.
Editor's Note: You can also view the Director’s Message from the National Institute on Neurological Disorders and Stroke.
Outstanding And Hopeful Summary! Great job!
Thanks for your ongoing leadership Dr. Hodes!
What functional biomarkers are being developed? Since cognitive functions dynamically proceed very rapidly across time durations, what video recordings of changing neuroglialvascular responses are measuring behavioral responses?
Thanks for the good question!
Several different biomarkers can provide insights into dynamic brain function.
See below and you can read more about NIA biomarker research at https://www.nia.nih.gov/news/topics/biomarkers.
Resting state functional magnetic resonance imaging (rsfMRI) uses blood oxygenation level dependent (BOLD) MRI to image changes in blood oxygenation. Increases and decreases over time in regional BOLD signal reflect changes in oxygen consumption (as well as neurovascular coupling) associated with neuronal activity. Correlation in BOLD signal between different brain regions reflects connectivity between those regions
Brain electrical activity due to neuronal activation can be studied with electroencephalography (EEG): an array of electrodes over the brain. The electrodes are usually placed on the skin and changes in voltage recorded over time, but electrodes are sometimes implanted in the brain, itself, to provide more precise localization of neuronal activity. A related method, magnetoencephalography (MEG) maps changes in magnetic fold associated with brain electrical activity
It’s also possible to map regional cerebral glucose metabolism (rCMGlu) with a neuroimaging method, positron emission tomography (PET) to image brain distribution of radioactively labelled fluorodeoxyglucose (FDG).
Why NIA is delaying notice of Awards for many grants including R01s, training grants and Career Development Awards? It is jeopardizing career progress of many investigators. The federal budget was approved in March and still many investigators are waiting for updates on their funding support. Why there are substantial delays? NIH mission to support research and ECRs.
Thank you for your comments. As you pointed out, the are many delays in the award process. This is primarily driven by the federal budget approval process. Technically the budget should be active for any Fiscal Year on October 1 thru September 30; if the budget approval is delayed as in a Continued Resolution (CR), everything gets backed up because we have to be extremely conservative in what we are allowed to pay during a CR.
This said, those grants that are approved in our October Council and even the January Council are all delayed; as well as all the Type 5s (non-competing awards which are paid at a reduced rate). Once the budget is approved, we then have to catch up; which translates into thousands of actions for our Grants Management staff. Also, as you pointed out in another comment, our pay line does change throughout the fiscal year (usually in a positive direction), but that again adds to the delay for the awardees in the higher pay line.
We understand that this is far from ideal for our extramural scientific community. We are making every effort in trying to get the grants out the door in a timely manner, but are bound by the granting rules and regulations tied to these awards.
Ken Santora, Director, NIA Division of Extramural Activities
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