This month, we reach an important milestone in dementia research – the 10th anniversary of the National Plan to Address Alzheimer’s Disease, which stemmed from the National Alzheimer’s Project Act (NAPA). The National Plan was created with an ambitious vision: to prevent and effectively treat Alzheimer’s disease (AD) by 2025. The plan and its yearly updates outline goals for a coordinated effort across federal and non-federal partners to accelerate research into Alzheimer’s disease and related dementias (AD/ADRD), and to better meet the needs of families currently facing these diseases.
Congress has signaled its commitment to AD/ADRD research by increasing funding to the NIH. In FY 2020, NIH spent about $2.87 billion on AD/ADRD research, more than 4-fold the amount from five years earlier. Since 2016, NINDS has released more than 60 funding opportunity announcements (FOAs) and initiated 11 large ADRD research consortia. I described some of these major initiatives in a previous message on NINDS contributions to ADRD research activities.
Although we have made much progress in understanding Alzheimer’s disease and related dementias, there is still much to be done to eliminate the burden of these diseases on the nation. The National Plan’s 10th anniversary is an opportune time to assess future research goals and take stock of all that has been accomplished.
Central to guiding AD/ADRD scientific priorities and spurring progress are a series of conferences every three years, held in collaboration with the National Institute on Aging (NIA). These summits help to set national research recommendations with timelines that reflect critical scientific priorities. As part of this process, NINDS leads triennial ADRD summits.
I had the chance to reflect on advances in AD/ADRD research in my opening remarks at the 2022 Alzheimer’s Disease-Related Dementias (ADRD) Summit took place on March 23-24.
ADRDs are the myriad dementias related to Alzheimer’s--progressive brain diseases that slowly destroy brain function, leading to problems with memory, language, and executive functioning. They include frontotemporal dementia (FTD), Lewy body dementia (LBD), vascular contributions to cognitive impairment and dementia (VCID), and mixed dementias. Although Alzheimer’s disease is the most common dementia diagnosis, ADRDs share many cognitive and pathological features. In fact, patients with a diagnosis of Alzheimer’s disease often present with different mixtures of brain pathologies. Since the first ADRD Summit in 2013, it has become increasingly clear that for most people affected by dementia, more than one brain change or disease process is likely to contribute, complicating both diagnosis and treatment.
This year’s Summit – recently featured in the NIH record – was a culminating effort from eight working groups comprised of over 100 research experts and stakeholders. Nearly 1,500 people registered to attend the virtual meeting, including researchers, clinicians, government officials, representatives from industry and nonprofit organizations, caregivers, and patients. This engaging summit enabled a thoughtful and rigorous discussion of draft ADRD research recommendations. Significant portions of the meeting were dedicated to public comment, which encouraged input from all stakeholders.
Based on input received at the Summit, the recommendations will be revised and presented to the National Neurological Disorders and Stroke Advisory Council (NANDSC) for consideration and approval and then submitted to the NAPA Council. Approved recommendations become research milestones in the National Plan to Address Alzheimer’s Disease. If you weren’t able to attend the 2022 ADRD Summit, recordings of the two-day meeting are now available: Day 1, Day 2.
This year’s summit included three special topics related to multiple etiology dementia: Dementia resulting from Traumatic Brain Injury (TBI), the impact of COVID-19 on AD/ADRD risk and outcomes, and a newly identified late-onset dementia (limbic-predominant age-associated TDP-43 encephalopathy, or LATE). The second day of the summit opened with a video made up of personal vignettes from AD/ADRD caregivers. They talked about their stories, struggles, and messages for the research community. If you have an opportunity, I encourage you to view it. It’s a reminder that input from those most intimately affected—caregivers and individuals with dementia—is vital to the National Plan. Their perspective can inform research design and help us better address their needs.
Over two days, ADRD Summit participants carefully examined the research needs of the field, reflecting the exciting period of AD/ADRD research we’ve entered. Much is known—the heterogeneity of AD/ADRD and more about the pathologies involved, for example—but much more remains to be learned. We are still unraveling the risk factors and biological mechanisms related to the development of dementia, and we continue working to advance potential therapies and prevention strategies. The thoughtful recommendations resulting from the summit will undoubtedly drive progress in the field.
Several forward-looking themes emerged from the Summit:
- Precise biomarkers that can identify the myriad underlying AD/ADRD disease processes remain a high priority.
- Increase the effectiveness and sophistication of AD/ADRD clinical trials, including increasing the use of pragmatic trial designs, which evaluate the effectiveness of interventions in real-life routine practice conditions.
- Clinical research should focus on both the immediate needs of individuals living with dementia, as well as longer-term research geared towards prevention or cures with personalized medicine that, by design, addresses diverse populations across the country.
- Improving health equity through AD/ADRD research was addressed by a panel and discussed prominently throughout the meeting with the consensus that achieving health equity is a major unmet need in AD/ADRD.
- More research is needed to understand the possible link between COVID-19 and long-term cognitive deficits, including the acceleration of Alzheimer’s disease pathology and symptoms.
I would like to acknowledge the efforts of Dr. Rod Corriveau, the NIH/NINDS Summit lead and Program Director for NINDS ADRD research; Dr. Natalia Rost, the Scientific Chair for this year’s summit; as well as NIA Director Dr. Richard Hodes, who has enabled such a productive collaboration between our Institutes. By the close of the ADRD Summit, I was left feeling optimistic that we stand at the cusp of significant breakthroughs in dementia research. With persistence and the passion of those in the field, guided by the framework provided by the National Plan to Address Alzheimer’s Disease, we have a clear path forward.
In commemoration of the 10th anniversary of the National Plan to Address Alzheimer's Disease, please also see a timeline of milestones and achievements from the Department of Health & Human Services, and an accompanying message from NIA Director Dr. Richard Hodes.
Progress in Dementia Research
A selection of recent AD/ADRD scientific advances:
- Progress in identifying and validating biomarkers. Biomarkers help us learn more about dementia risk in individuals and thus set the stage for better treatments. Diagnostic biomarkers are measurements that can be used to understand what kind of pathology is occurring in the brain. They’re of particular importance given the mixed pathologies in ADRD.
- Research has revealed accurate ways of testing spinal fluid or skin biopsies to detect the synuclein aggregates that are associated with Parkinson's disease and Lewy body disease.
- Certain radioactive scans detect dopamine loss in people who have Lewy body disease, distinguishing it from Alzheimer's disease.
- Predictive studies have examined evidence of Alzheimer pathology in people with Lewy body and Parkinson's disease that contributes to problems with cognition.
- Progress in identifying early signs of VCID and preventing vascular-related cognitive decline. We know that intensively lowering blood pressure in mid-life decreases the risk of cognitive impairment and lessens accumulation of white matter lesions, a known vascular contribution to cognitive impairment and dementia (VCID).
- In 2016, NINDS launched a public health campaign, Mind Your Risks, to raise awareness of the connection between high blood pressure in midlife and risk for stroke and dementia later in late. We are currently updating the campaign to focus on Black men between the ages of 28-45, who are at the highest risk for developing high blood pressure.
- To improve diagnosis of small vessel disease (a contributor to dementia), the NINDS and NIA-supported MarkVCID consortium has developed and is currently validating different biomarkers for use in dementia clinical trials.
- MRIs can track changes in the white matter of the brain commonly associated with hypertension and cerebrovascular disease, thus determining whether a therapy affects disease progression.
- Uncovering the role of TDP-43—researchers recently discovered that the mislocalization of the protein TDP-43 alters the genetic instructions for UNC13A, a protein whose genetic variant has been linked to AD. This provides a possible therapeutic target with implications for treating diseases such as frontotemporal dementia (FTD), and other forms of dementia including TDP-43 proteinopathy in commonly occurring dementias (LATE).
- Advances in cutting-edge neurotechnologies are providing new AD/ADRD research opportunities. Several AD/ADRD projects, major programs, and funding opportunities are leveraging new technologies that can explore cell-by-cell and circuit-by-circuit changes that lead to disease. These technologies include neurovascular imaging and functional and longitudinal single cell characterization, among others.