CUHK Researcher participates in the Consensus study on Research Priorities for Preventing and Treatment Alzheimer’s Disease and Related Dementia under the Board on Health Science Policy at the U.S. National Academy of Medicine

Dementia imposes a significant emotional and financial burden on individuals, families, and communities, a burden that is expected to increase with the aging of the global population. Addressing Alzheimer’s disease and related dementias (AD/ADRD), a group of degenerative neurological conditions, is recognized as a critical priority in biomedical research. The National Institutes of Health (NIH) has dedicated substantial funding to this area over the past decade, laying a groundwork of understanding that offers further opportunities for exploration. Despite these efforts, the rate of advancement has not kept pace with the mounting needs of individuals affected by AD/ADRD and those vulnerable to these conditions.

In response to a congressional request, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) commissioned the National Academies of Sciences, Engineering, and Medicine to form a committee. This committee was tasked with evaluating the current biomedical research landscape and identifying key research areas to improve the prevention and treatment of AD/ADRD.

Dr. Kim Hei-Man CHOW, serving as the National Academy of Medicine International Health Policy Fellow, actively contributed to discussions and collaborated on drafting the report alongside the Committee and the Academy’s Staffs throughout the year 2024. The resulting document, named "Preventing and Treating Dementia: Research Priorities to Accelerate Progress," outlines a series of research priorities and associated recommendations designed to overcome obstacles to progress. It was publicly released in December 2024 after vigorous peer review process.

AD/ADRD Research Priorities

The 11 research priorities outlined in the report mirror the collective viewpoint of the committee regarding the most auspicious areas for scientific exploration, aimed at propelling the field forward and bolstering public health. These research priorities are centered on advancing the comprehension of AD/ADRD prevention and treatment. Nevertheless, the committee's primary aim was to ensure that these research endeavors culminate in tangible enhancements in the lives of individuals already grappling with AD/ADRD, while also striving to avert the onset of these conditions in others.

In light of the prevalent occurrence of mixed pathologies among elderly individuals, these research priorities underscore opportunities spanning the entire spectrum of AD/ADRD, rather than exclusively targeting distinct dementia subtypes:

1. Develop better tools, such as innovative biomarker tests and digital assessment technologies, to track brain health throughout all stages of life, enabling widespread screening, prediction, and diagnosis of AD/ADRD.
2. Incorporate advancements in clinical research methodologies and tools to collect data from real-world clinical environments, enhancing insights for future research endeavors.
3. Uncover the factors influencing the risk of AD/ADRD in diverse populations, with a specific focus on understudied and disproportionately impacted groups, to comprehend disease variations, including molecular subcategories and variations in environmental exposures. This exploration aims to pinpoint prevention opportunities and promote equity in health research.
4. Profile the exposome and gene-environment interactions across individuals' lifespans to gain a deeper understanding of biological mechanisms, identifying avenues to decrease the risk of AD/ADRD and enhance resilience.
5. Elucidate the genetic and other biological mechanisms that contribute to resilience and resistance, pinpointing new targets and effective strategies for the prevention and treatment of AD/ADRD.
6. Develop comprehensive molecular and cellular causal models to steer the identification of shared mechanisms underlying AD/ADRD, facilitating the validation of novel targets for prevention and treatment.
7. Integrate innovative methodologies and cutting-edge tools into the planning, design, and execution of research studies to expedite the discovery of effective interventions.
8. Advance the development and evaluation of combination therapies, which include both pharmaceutical and non-pharmaceutical approaches, to comprehensively address the multifaceted complexity of AD/ADRD
9. Assess precision medicine strategies for the prevention and treatment of AD/ADRD to pinpoint interventions likely to be beneficial for specific subgroups of individuals.
10. Promote the adoption of standardized outcome measures for appraising interventions that are precise, individual-focused, clinically significant, and align with the priorities of individuals at risk of or living with AD/ADRD.
11. Investigate the causal impacts of public health interventions on the overall incidence of dementia, particularly among underrepresented or disproportionately affected populations.

Strategies to overcome barriers to progress on AD/ADRD research priorities

In addition to the recommendations on research priorities, the report also presents interrelated suggestions aimed at addressing overarching obstacles to advancing the specified scientific research priorities. In summary, these include:

1. Enhancing longitudinal and intervention research—Long-term cohort studies serve as a crucial tool for gaining a holistic understanding of brain health throughout one's lifetime. As a result, the report suggests that the NIH should give precedence to funding longitudinal research endeavors. This involves utilizing data from current cohorts focusing on various health conditions and establishing new, diverse cohorts with multidimensional aspects to fill the existing knowledge voids concerning the factors impacting brain health across the lifespan.
2. Breaking down barriers to the acceleration of clinical research— Numerous parties play a role in AD/ADRD research, underscoring the need for heightened collaboration to expedite discoveries, hasten the development of effective interventions, and close funding disparities. The report advocates for the NIH to persist in spearheading collaborations among diverse stakeholders to expedite the progression of promising AD/ADRD interventions into clinical trials. Furthermore, it suggests expanding the adoption of innovative strategies to enhance the efficacy of clinical trials.
3. Breaking down silos through collaborative, multidisciplinary research— The report's research priorities do not center on specific types of dementia but rather underscore research opportunities spanning the spectrum of AD/ADRD. This shift aims to move beyond compartmentalized approaches and address the prevalent occurrence of mixed dementia, where multiple pathologies coincide in the brain. According to the report, it is believed that the majority of dementia cases in individuals aged over 65 involve mixed dementia. To combat the existing isolation of research efforts and expedite the advancement of interventions, the report suggests that innovative funding approaches and incentives promoting collaboration will be essential. Effective models, such as multi-institute research consortia fostering coordination and data exchange, as well as public-private partnerships, have exhibited encouraging results, according to the report.
4. Fostering inclusive research—A thorough comprehension of population-level variances in AD/ADRD is crucial; however, disproportionately impacted groups are consistently marginalized in research efforts. The absence of diverse study populations could compromise the generalizability of findings, potentially worsening health inequalities. To address this issue, the report suggests that the NIH promote and steer the adoption of inclusive research methodologies. It recommends that NIH-funded researchers embrace these practices to enhance the inclusivity of clinical and public health research, guaranteeing that study populations accurately reflect those at risk for and affected by AD/ADRD.
5. Enhancing the accessibility and usability of biological samples, data and knowledge to maximize the returns from AD/ADRD research— Effective collaboration in research is hindered when data and samples are not shared. The report suggests that the NIH should establish and back an NIH workgroup to address barriers that obstruct access to data from AD/ADRD research, fostering collaboration. However, mere accessibility is insufficient to ensure the usability of data from prior AD/ADRD studies. To enhance data usability, the report proposes that the NIH invest in various strategies outlined in the detailed report. Additionally, it advises the NIA and NINDS to broaden their support for the collection and preservation of valuable biological samples from NIH-funded AD/ADRD research in a way that optimizes their potential for future utilization.
6. Catalyzing transformational change through innovation in AD/ADRD research— Driving advancements in AD/ADRD prevention and treatment demands a significant shift. Consequently, the report suggests that the NIH should leverage current funding mechanisms and additional incentives to catalyze innovation throughout every phase of AD/ADRD research. For instance, the expansion of public-private partnerships could harness expertise from both industry and academia, incorporating successful strategies from diverse programs and sectors. Additionally, NIH could integrate innovations and resources developed by entities such as the Advanced Research Projects Agency for Health (ARPA-H) into NIH-funded research on Alzheimer's disease and related dementias (AD/ADRD), encompassing advancements tailored to dementia as well as those adaptable from different domains. Collaborating with foundations and other research financiers, NIH could establish cohesive funding channels for pioneering, high-risk research initiatives.

In summary, while the past decade has witnessed notable advancements in AD/ADRD prevention and treatment, there still exists a considerable demand for further progress. By fostering collaborative initiatives throughout the biomedical research sector and implementing the strategies delineated in this report, there is potential to envision a future where dementia is both preventable and treatable.

For the complete report, please visit: https://nap.nationalacademies.org/catalog/28588/preventing-and-treating-dementia-research-priorities-to-accelerate-progress. The study—undertaken by the Committee on Research Priorities for Preventing and Treating Alzheimer’s Disease and Related Dementias—was sponsored by the U.S. Department of Health and Human Services. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, engineering, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.

Brief biography of Dr. Kim Hei-Man Chow

Dr. Kim Hei-Man Chow is an Assistant Professor in the School of Life Sciences, also an Executive Committee member of Gerald Choa Neuroscience Institute (GCNI) at CUHK. She received her graduate training at the University of Hong Kong, pursued postdoctoral training at Cornell University, and later held a research assistant professorship at the Hong Kong University of Science and Technology. Dr. Chow has been honored with multiple international fellowships, including the US National Academy of Medicine International Health Policy Fellowship, US Alzheimer's Association Research Fellowship, World Economic Forum Global Future Council Fellowship, and China NSFC Excellent Young Scientist Fund.

Dr. Kim Hei-Man Chow. The photo was taken at the National Academy of Sciences Building.

(From left) Dr. Michael McGinnis, The Leonard D. Schaeffer Executive Officer of the National Academy of Medicine (NAM), Dr. Kim Hei-Man Chow, NAM International Health Policy Fellow, and Dr. Gregg Margolis, Director of Health Policy Fellowships and Leadership Programs of the NAM. The photo was taken at the Keck Centre of the National Academies.

(From right) Dr. Victor J. Dzau, the President of the National Academy of Medicine (NAM) and Dr. Kim Hei-Man Chow, NAM International Health Policy Fellow. The photo was taken at the George and Cynthia Mitchell Conference Center of the Keck Centre of the National Academies.