As people live longer, society will grapple with unprecedented demand for prevention, diagnosis and treatment pertaining to certain neurological conditions. For example, researchers expect the number of people living with Alzheimer’s disease to triple by 2025.
Thirteen percent of people over the age of 65 develop the disease, but a portion of the remaining 87% will struggle with cognitive decline due to the normal aging process. They may forget names, become disoriented by simple tasks, or find it difficult to manage their finances. The effects of cognitive decline will have an adverse impact on millions of individuals’ quality of life and exact a toll on the public healthcare system.
With this coming wave of increased need in mind, neurological research funders are pushing the limits of what the field can do to support an aging population. The McKnight Brain Research Foundation (MBRF) and the American Federation for Aging Research (AFAR) are two such grantmakers tackling these looming challenges by ramping up support for cognitive aging research. “Our focus is on how to permit people to remain cognitively healthy for as long as they can,” said MBRF Chair Emeritus J. Lee Dockery, MD. “We’re the only organization that differentiates age-related cognitive decline and memory loss from other neurodegenerative disorders.”
AFAR acknowledges that the more researchers and physicians understand the basic biology of aging, the better equipped they’ll be to delay many chronic diseases, including stroke, Alzheimer’s disease, cancer and diabetes. Its goal is to “establish the field of aging researchers who are looking into the biological mechanisms of why and how we age, and how that affects the diseases of aging, including cognitive decline,” said Executive Director Stephanie Lederman. “There has been a considerable amount of research to the point now that we are on the verge of some important breakthroughs. It’s a very exciting time.”
Long-standing commitments to cognitive aging research
The Orlando-based MBRF defines cognitive aging as “a natural process that can have both positive and negative effects, and these effects vary widely from person to person.” It was established in 1999 by Evelyn F. McKnight, the widow of former 3M Chairman William L. McKnight, who founded the Minneapolis-based McKnight Foundation in 1953. Together with its partners, the MBRF has funded more than $180 million in cognitive aging research since its inception.
The foundation has established Evelyn F. McKnight Brain Institutes at the University of Alabama at Birmingham, the University of Arizona, and the University of Miami; and the Evelyn F. and William L. McKnight Brain Institute at the University of Florida. Its partners include the National Institute on Aging through the Foundation for the National Institutes of Health, the American Academy of Neurology, the American Brain Foundation, and AFAR.
The New York City-based AFAR was launched in 1981 by cardiologist and American Heart Association cofounder Irving Wright. “At the time, there was very little knowledge in the field,” Lederman told me. “But he knew that baby boomers would be getting older, so it was important to better understand how we could keep people healthier for a longer period of time.” In the intervening years, it has awarded $193 million in research grants to over 4,350 investigators. AFAR maintains a list of funding opportunities on its site.
Distinguishing cognitive decline from other conditions
Madhav Thambisetty, MD, Ph.D. is an adjunct professor of neurology at the Johns Hopkins University School of Medicine and leads a research group working on drug discovery in Alzheimer’s disease at the National Institute on Aging. Thambisetty said that when he joined the MBRF board as a trustee in 2015, “the biggest challenge was, how do we define the distinction between what is normal aging and what is Alzheimer’s disease?”
Getting this distinction right or wrong can lead to downstream consequences. Physicians may misdiagnose a patient and prescribe expensive treatments that do not address the underlying condition, or individuals may worry they have Alzheimer’s when, in fact, they’re simply experiencing the effects of aging. This uncertainty can compel individuals to put their faith in unproven treatments or outright scams to stay mentally sharp. “Don’t forget the jellyfish,” Lederman said, alluding to a jellyfish memory supplement that turned out to be a hoax.
The lack of a clear delineation between normal aging and conditions like Alzheimer’s can also stymie efforts to generate private support since many funders seek to galvanize treatments for established diseases. “So much of the funding opportunities for diseases are from benefactors who’ve had a relative or someone that they know who has been a victim of a disease, so they support that cause, and it’s justified that they do so,” Dockery said. “But we don’t have many partners that are interested in funding and investigating aging itself.”
“It doesn’t happen overnight”
The MBRF and AFAR are working to fix this disconnect. Cognizant of funders’ desire to bring promising treatments to market, Thambisetty said that the MBRF’s grantmaking strategy “ensures that the people that we fund, whether individual researchers or the McKnight Brain Research Institutes, have a clear translational focus in all of the research that they do.”
MBRF stakeholders also acknowledge that translational research cannot exist without fundamental basic research, which is typically defined as studies that span disciplines and lead to new knowledge. As a result, Thambisetty said, the foundation “tries to balance our funding portfolio to encourage basic science that has a promise of clinical translation.”
Administered in partnership with AFAR, the McKnight Brain Research Foundation Innovator Awards in Cognitive Aging and Memory Loss bridges these two research approaches. “One of the awards is for basic science and the other is for clinical translational research,” Thambisetty said. “We recognize that both have to be promoted, but one can inform the other, and they can converge and advance meaningful translational findings.”
Looking back on his tenure so far, Thambisetty believes the field of cognitive aging has made tremendous progress since he joined the MBRF board seven years ago. “We are now at the stage where we may have relatively noninvasive, highly accurate tests that allow us to make the distinction between who has pathology in their brain, who’s likely to have Alzheimer’s disease, and who may not have the telltale pathological signs of the disease,” he said.
AFAR, which also funds basic and translational research, embraces the term “geroscience,” which it defines as “a research paradigm based in addressing the biology of aging and biology of age-related diseases.” The idea here is that donors will be more supportive of age-related research once they realize that the biological processes of aging are the greatest risk factors for many chronic diseases. “Interventions that slow the aging processes would dramatically lower healthcare costs, perhaps more than the cure of any single disease, while significantly improving quality of life,” its site reads.
I spoke with MBRF and AFAR reps for an upcoming IP white paper on the state of funding for neurological research organizations. In practically every conversation, leaders implored fundraisers to mix hope-based messaging with healthy doses of pragmatism and patience. “It’s a matter of education,” Lederman said. “So many of the breakthroughs we’ve seen took years to be developed with support from the private sector. It doesn’t happen overnight. That’s just the nature of research.”
