Alzheimer’s prevention may be less about new drugs, more about income, zip code and education
That your risk of Alzheimer’s disease depends on your salary, what you ate as a child, or the block where you live may seem implausible. But researchers are discovering that social determinants of health (SDOH) play an outsized role in Alzheimer’s disease and related dementias, possibly more than age, and new strategies are emerging for how to address these factors.
At the 2022 Alzheimer’s Association International Conference, a series of presentations offered evidence that a string of socioeconomic factors—such as employment status, social support networks, education and home ownership—significantly affected dementia risk, even when adjusting data for genetic risk. What’s more, memory declined more rapidly in people who earned lower wages and slower in people who had parents of higher socioeconomic status.
In 2020, a first-of-its kind study in JAMA linked Alzheimer’s incidence to “neighborhood disadvantage,” which is based on SDOH indicators. Through autopsies, researchers analyzed brain tissue markers related to Alzheimer’s and found an association with these indicators. In 2022, Ryan Powell, the lead author of that study, published further findings that neighborhood disadvantage was connected with having more neurofibrillary tangles and amyloid plaques, the main pathological features of Alzheimer's disease.
As of yet, little is known about the biological processes behind this, says Powell, director of data science at the Center for Health Disparities Research at the University of Wisconsin School of Medicine and Public Health. “We know the association but not the direct causal pathway.”
The corroborative findings keep coming. In a Nature study published a few months after Powell’s study, every social determinant investigated affected Alzheimer’s risk except for marital status. The links were highest for income, education, and occupational status.
Clinical trials on new Alzheimer’s medications get all the headlines but preventing dementia through policy and public health interventions should not be underestimated.
The potential for prevention is significant. One in three older adults dies with Alzheimer's or another dementia—more than breast and prostate cancers combined. Further, a 2020 report from the Lancet Commission determined that about 40 percent of dementia cases could theoretically be prevented or delayed by managing the risk factors that people can modify.
Take inactivity. Older adults who took 9,800 steps daily were half as likely to develop dementia over the next 7 years, in a 2022 JAMA study. Hearing loss, another risk factor that can be managed, accounts for about 9 percent of dementia cases.
Clinical trials on new Alzheimer’s medications get all the headlines but preventing dementia through policy and public health interventions should not be underestimated. Simply slowing the course of Alzheimer’s or delaying its onset by five years would cut the incidence in half, according to the Global Council on Brain Health.
Minorities Hit the Hardest
The World Health Organization defines SDOH as “conditions in which people are born, work, live, and age, and the wider set of forces and systems shaping the conditions of daily life.”
Anyone who exists on processed food, smokes cigarettes, or skimps on sleep has heightened risks for dementia. But minority groups get hit harder. Older Black Americans are twice as likely to have Alzheimer’s or another form of dementia as white Americans; older Hispanics are about one and a half times more likely.
This is due in part to higher rates of diabetes, obesity, and high blood pressure within these communities. These diseases are linked to Alzheimer’s, and SDOH factors multiply the risks. Blacks and Hispanics earn less income on average than white people. This means they are more likely to live in neighborhoods with limited access to healthy food, medical care, and good schools, and suffer greater exposure to noise (which impairs hearing) and air pollution—additional risk factors for dementia.
Related Reading: The Toxic Effects of Noise and What We're Not Doing About it
Plus, when Black people are diagnosed with dementia, their cognitive impairment and neuropsychiatric symptom are more advanced than in white patients. Why? Some African-Americans delay seeing a doctor because of perceived discrimination and a sense they will not be heard, says Carl V. Hill, chief diversity, equity, and inclusion officer at the Alzheimer’s Association.
Misinformation about dementia is another issue in Black communities. The thinking is that Alzheimer’s is genetic or age-related, not realizing that diet and physical activity can improve brain health, Hill says.
African Americans are severely underrepresented in clinical trials for Alzheimer’s, too. So, researchers miss the opportunity to learn more about health disparities. “It’s a bioethical issue,” Hill says. “The people most likely to have Alzheimer’s aren’t included in the trials.”
The Cure: Systemic Change
People think of lifestyle as a choice but there are limitations, says Muniza Anum Majoka, a geriatric psychiatrist and assistant professor of psychiatry at Yale University, who published an overview of SDOH factors that impact dementia. “For a lot of people, those choices [to improve brain health] are not available,” she says. If you don’t live in a safe neighborhood, for example, walking for exercise is not an option.
Hill wants to see the focus of prevention shift from individual behavior change to ensuring everyone has access to the same resources. Advice about healthy eating only goes so far if someone lives in a food desert. Systemic change also means increasing the number of minority physicians and recruiting minorities in clinical drug trials so studies will be relevant to these communities, Hill says.
Based on SDOH impact research, raising education levels has the most potential to prevent dementia. One theory is that highly educated people have a greater brain reserve that enables them to tolerate pathological changes in the brain, thus delaying dementia, says Majoka. Being curious, learning new things and problem-solving also contribute to brain health, she adds. Plus, having more education may be associated with higher socioeconomic status, more access to accurate information and healthier lifestyle choices.
New Strategies
The chasm between what researchers know about brain health and how the knowledge is being applied is huge. “There’s an explosion of interest in this area. We’re just in the first steps,” says Powell. One day, he predicts that physicians will manage Alzheimer’s through precision medicine customized to the patient’s specific risk factors and needs.
Raina Croff, assistant professor of neurology at Oregon Health & Science University School of Medicine, created the SHARP (Sharing History through Active Reminiscence and Photo-imagery) walking program to forestall memory loss in African Americans with mild cognitive impairment or early dementia.
Participants and their caregivers walk in historically black neighborhoods three times a week over six months. A smart tablet provides information about “Memory Markers” they pass, such as the route of a civil rights march. People celebrate their community and culture while “brain health is running in the background,” Croff says.
Photos and memory prompts engage participants in the SHARP program.
OHSU/Kristyna Wentz-Graff
The project began in 2015 as a pilot study in Croff’s hometown of Portland, Ore., expanded to Seattle, and will soon start in Oakland, Calif. “Walking is good for slowing [brain] decline,” she says. A post-study assessment of 40 participants in 2017 showed that half had higher cognitive scores after the program; 78 percent had lower blood pressure; and 44 percent lost weight. Those with mild cognitive impairment showed the most gains. The walkers also reported improved mood and energy along with increased involvement in other activities.
It’s never too late to reap the benefits of working your brain and being socially engaged, Majoka says.
In Milwaukee, the Wisconsin Alzheimer’s Institute launched the The Amazing Grace Chorus® to stave off cognitive decline in seniors. People in early stages of Alzheimer’s practice and perform six concerts each year. The activity provides opportunities for social engagement, mental stimulation, and a support network. Among the benefits, 55 percent reported better communication at home and nearly half of participants said they got involved with more activities after participating in the chorus.
Private companies are offering intervention services to healthcare providers and insurers to manage SDOH, too. One such service, MyHello, makes calls to at-risk people to assess their needs—be it food, transportation or simply a friendly voice. Having a social support network is critical for seniors, says Majoka, noting there was a steep decline in cognitive function among isolated elders during Covid lockdowns.
About 1 in 9 Americans age 65 or older live with Alzheimer’s today. With a surge in people with the disease predicted, public health professionals have to think more broadly about resource targets and effective intervention points, Powell says.
Beyond breakthrough pills, that is. Like Dorothy in Kansas discovering happiness was always in her own backyard, we are beginning to learn that preventing Alzheimer’s is in our reach if only we recognized it.
WENDY SCHMIDT is a philanthropist and investor who has spent more than a dozen years creating innovative non-profit organizations to solve pressing global environmental and human rights issues. Recognizing the human dependence on sustaining and protecting our planet and its people, Wendy has built organizations that work to educate and advance an understanding of the critical interconnectivity between the land and the sea. Through a combination of grants and investments, Wendy's philanthropic work supports research and science, community organizations, promising leaders, and the development of innovative technologies. Wendy is president of The Schmidt Family Foundation, which she co-founded with her husband Eric in 2006. They also co-founded Schmidt Ocean Institute and Schmidt Futures.
Editors: The pandemic has altered the course of human history and the nature of our daily lives in equal measure. How has it affected the focus of your philanthropy across your organizations? Have any aspects of the crisis in particular been especially galvanizing as you considered where to concentrate your efforts?
Wendy: The COVID-19 pandemic has made the work of our philanthropy more relevant than ever. If anything, the circumstances of this time have validated the focus we have had for nearly 15 years. We support the need for universal access to clean, renewable energy, healthy food systems, and the dignity of human labor and self-determination in a world of interconnected living systems on land and in the Ocean we are only beginning to understand.
When you consider the disproportionate impact of the COVID-19 virus on people who are poorly paid, poorly housed, with poor nutrition and health care, and exposed to unsafe conditions in the workplace—you see clearly how the systems that have been defining how we live, what we eat, who gets healthcare and what impacts the environment around us—need to change.
"This moment has propelled broad movements toward open publication and open sharing of data and samples—something that has always been a core belief in how we support and advance science."
If the pandemic teaches us anything, we learn what resilience looks like, and the essential role for local small businesses including restaurants, farms and ranches, dairies and fish markets in the long term vitality of communities. There is resonance, local economic benefit, and also accountability in these smaller systems, with shorter supply chains and less vertical integration.
The consolidation of vertically integrated business operations for the sake of global efficiency reveals its essential weakness when supply chains break down and the failure to encourage local economic centers leads to intense systemic disruption and the possibility of collapse.
Editors: For scientists, one significant challenge has been figuring out how to continue research, if at all, during this time of isolation and distancing. Yet, your research vessel Falkor, of the Schmidt Ocean Institute, is still on its expedition exploring the Coral Sea Marine Park in Australia—except now there are no scientists onboard. What was the vessel up to before the pandemic hit? Can you tell us more about how they are continuing to conduct research from afar now and how that's going?
Wendy: We have been extremely fortunate at Schmidt Ocean Institute. When the pandemic hit in March, our research vessel, Falkor, was already months into a year-long program to research unexplored deep sea canyons around Australia and at the Great Barrier Reef. We were at sea, with an Australian science group aboard, carrying on with our mission of exploration, discovery and communication, when we happened upon what we believe to be the world's longest animal—a siphonophore about 150 feet long, spiraling out at a depth of about 2100 feet at the end of a deeper dive in the Ningaloo Canyon off Western Australia. It was the kind of wondrous creature we find so often when we conduct ROV dives in the world's Ocean.
For more than two months this year, Falkor was reportedly the only research vessel in the world carrying on active research at sea. Once we were able to dock and return the science party to shore, we resumed our program at sea offering a scheduled set of now land-based scientists in lockdown in Australia the opportunity to conduct research remotely, taking advantage of the vessel's ship to shore communications, high resolution cameras and live streaming video. It's a whole new world, and quite wonderful in its own way.
Editors: Normally, 10–15 scientists would be aboard such a vessel. Is "remote research" via advanced video technology here to stay? Are there any upsides to this "new normal"?
Wendy: Like all things pandemic, remote research is an adaptation for what would normally occur. Since we are putting safety of the crew and guest scientists at the forefront, we're working to build strong remote connections between our crew, land based scientists and the many robotic tools on board Falkor. There's no substitute for in person work, but what we've developed during the current cruise is a pretty good and productive alternative in a crisis. And what's important is that this critical scientific research into the deep sea is able to continue, despite the pandemic on land.
Editors: Speaking of marine expeditions, you've sponsored two XPRIZE competitions focused on ocean health. Do you think challenge prizes could fill gaps of the global COVID-19 response, for example, to manufacture more testing kits, accelerate the delivery of PPE, or incentivize other areas of need?
Wendy: One challenge we are currently facing is that innovations don't have the funding pathway to scale, so promising ideas by entrepreneurs, researchers, and even major companies are being developed too slowly. Challenge prizes help raise awareness for problems we are trying to solve and attract new people to help solve those problems by giving them a pathway to contribute.
One idea might be for philanthropy to pair prizes and challenges with an "advanced market commitment" where the government commits to a purchase order for the innovation if it meets a certain test. That could be deeply impactful for areas like PPE and the production of testing kits.
Editors: COVID-19 testing, especially, has been sorely needed, here in the U.S. and in developing countries as well as low-income communities. That's why we're so intrigued by your Schmidt Science Fellows grantee Hal Holmes and his work to repurpose a new DNA technology to create a portable, mobile test for COVID-19. Can you tell us about that work and how you are supporting it?
Wendy: Our work with Conservation X Labs began years ago when our foundation was the first to support their efforts to develop a handheld DNA barcode sensor to help detect illegally imported and mislabeled seafood and timber products. The device was developed by Hal Holmes, who became one of our Schmidt Science Fellows and is the technical lead on the project, working closely with Conservation X Labs co-founders Alex Deghan and Paul Bunje. Now, with COVID-19, Hal and team have worked with another Schmidt Science Fellow, Fahim Farzardfard, to repurpose the technology—which requires no continuous power source, special training, or a lab—to serve as a mobile testing device for the virus.
The work is going very well, manufacturing is being organized, and distribution agreements with hospitals and government agencies are underway. You could see this device in use within a few months and have testing results within hours instead of days. It could be especially useful in low-income communities and developing countries where access to testing is challenging.
Editors: How is Schmidt Futures involved in the development of information platforms that will offer productive solutions?
Wendy: In addition to the work I've mentioned, we've also funded the development of tech-enabled tools that can help the medical community be better prepared for the ongoing spike of COVID cases. For example, we funded EdX and Learning Agency to develop an online training to help increase the number of medical professionals who can operate ventilators. The first course is being offered by Harvard University, and so far, over 220,000 medical professionals have enrolled. We have also invested in informational platforms that make it easier to contain the spread of the disease, such as our work with Recidiviz to model the impact of COVID-19 in prisons and outline policy steps states could take to limit the spread.
Information platforms can also play a big part pushing forward scientific research into the virus. For example, we've funded the UC Santa Cruz Virus Browser, which allows researchers to examine each piece of the virus and see the proteins it creates, the interactions in the host cell, and — most importantly — almost everything the recent scientific literature has to say about that stretch of the molecule.
Editors: The scale of research collaboration and the speed of innovation today seem unprecedented. The whole science world has turned its attention to combating the pandemic. What positive big-picture trends do you think or hope will persist once the crisis eventually abates?
Wendy: As in many areas, the COVID crisis has accelerated trends in the scientific world that were already well underway. For instance, this moment has propelled broad movements toward open publication and open sharing of data and samples—something that has always been a core belief in how we support and advance science.
We believe collaboration is an essential ingredient for progress in all areas. Early in this pandemic, Schmidt Futures held a virtual gathering of 160 people across 70 organizations in philanthropy, government, and business interested in accelerating research and response to the virus, and thought at the time, it's pretty amazing this kind of thing doesn't go all the time. We are obviously going to go farther together than on our own...
My husband, Eric, has observed that in the past two months, we've all catapulted 10 years forward in our use of technology, so there are trends already underway that are likely accelerated and will become part of the fabric of the post-COVID world—like working remotely; online learning; increased online shopping, even for groceries; telemedicine; increasing use of AI to create smarter delivery systems for healthcare and many other applications in a world that has grown more virtual overnight.
"Our deepest hope is that out of these alarming and uncertain times will come a renewed appreciation for the tools of science, as they help humans to navigate a world of interconnected living systems, of which viruses are a large part."
We fully expect these trends to continue and expand across the sciences, sped up by the pressures of the health crisis. Schmidt Ocean Institute and Schmidt Futures have been pressing in these directions for years, so we are pleased to see the expansions that should help more scientists work productively, together.
Editors: Trying to find the good amid a horrible crisis, are there any other new horizons in science, philanthropy, and/or your own work that could transform our world for the better that you'd like to share?
Wendy: Our deepest hope is that out of these alarming and uncertain times will come a renewed appreciation for the tools of science, as they help humans to navigate a world of interconnected living systems, of which viruses are a large part. The more we investigate the Ocean, the more we look deeply into what lies in our soils and beneath them, the more we realize we do not know, and moreover, how vulnerable humanity is to the forces of the natural world.
Philanthropy has an important role to play in influencing how people perceive our place in the world and understand the impact of human activity on the rest of the planet. I believe it's philanthropy's role to take risks, to invest early in innovative technologies, to lead where governments and industry aren't ready to go yet. We're fortunate at this time to be able to help those working on tools to better diagnose and treat the virus, and to invest in those working to improve information systems, so citizens and policy makers can make better decisions that can reduce impacts on families and institutions.
From all we know, this isn't likely to be the last pandemic the world will see. It's been said that a crisis comes before change, and we would hope that we can play a role in furthering the work to build systems that are resilient—in information, energy, agriculture and in all the ways we work, recreate, and use the precious resources of our planet.
[This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
[Editor's Note: Welcome to Leaps of the Past, a new monthly column that spotlights the fascinating backstory behind a medical or scientific breakthrough from history.]
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Until about 40 years ago, ulcers were a mysterious – and sometimes deadly – ailment. Found in a person's stomach lining or intestine, ulcers are small sores that cause a variety of painful symptoms, such as vomiting, a burning or aching sensation, internal bleeding and stomach obstruction. Patients with ulcers suffered for years without a cure and sometimes even needed their stomachs completely removed to rid them from pain.
"To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat."
In the early 1980s, the majority of scientists thought that ulcers were caused by stress or poor diet. But a handful of scientists had a different theory: They believed that ulcers were caused by a corkscrew-shaped bacterium called Helicobacter pylori, or H. pylori for short. Robin Warren, a pathologist, and Barry Marshall, an internist, were the two pioneers of this theory, and the two teamed up to study H. pylori at the Royal Perth Hospital in 1981.
The pair started off by trying to culture the bacteria in the stomachs of patients with gastritis, an inflammation of the stomach lining and a precursor to developing an ulcer. Initially, the microbiologists involved in their clinical trial found no trace of the bacteria from patient samples – but after a few weeks, the microbiologists discovered that their lab techs had been throwing away the cultures before H. pylori could grow. "After that, we let the cultures grow longer and found 13 patients with duodenal ulcer," said Marshall in a later interview. "All of them had the bacteria."
Marshall and Warren also cultured H. pylori in the stomachs of patients with stomach cancer. They observed that "everybody with stomach cancer developed it on a background of gastritis. Whenever we found a person without Helicobacter, we couldn't find gastritis either." Marshall and Warren were convinced that H. pylori not only caused gastritis and peptic ulcers, but stomach cancer as well.
But when the team presented their findings at an annual meeting of the Royal Australasian College of Physicians in Perth, they were mostly met with skepticism. "To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat," Marshall said. "The idea was too weird."
Warren started treating his gastritis patients with antibiotics with great success – but other internists remained doubtful, continuing to treat their patients with antacids instead. Making matters more complicated, neither Warren nor Marshall could readily test their theory, since the pair only had lab mice at their disposal and H. pylori infects only humans and non-human primates, such as rhesus monkeys.
So Marshall took an unconventional approach. First, he underwent two tests to get a baseline reading of his stomach, which showed no presence of H. pylori. Then, Marshall took some H. pylori bacteria from a petri dish, mixed it with beef extract to create a broth, and gulped it down. If his theory was correct, a second gastric biopsy would show that his stomach was overrun with H. pylori bacteria, and a second endoscopy would show a painfully inflamed stomach – gastritis.
Less than a week later, Marshall started feeling sick. "I expected to develop an asymptomatic infection," he later said in an interview published in the Canadian Journal of Gastroenterology. "… [but] after five days, I started to have bloating and fullness after the evening meal, and my appetite decreased. My breath was bad and I vomited clear watery liquid, without acid, each morning."
At his wife's urging, Marshall started on a regimen of antibiotics to kill off the burgeoning bacteria, so a follow-up biopsy showed no signs of H. pylori. A follow-up endoscopy, however, showed "severe active gastritis" along with epithelial damage. This was the smoking gun other clinicians needed to believe that H. pylori caused gastritis and stomach cancer. When they began to treat their gastritis patients with antibiotics, the rate of peptic ulcers in the Australian population diminished by 70 percent.
Today, antibiotics are the standard of care for anyone afflicted with gastritis.
In 2005, Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery of H. Pylori and its role in developing gastritis and peptic ulcers. "Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors," the Nobel Prize Committee said.
Today, antibiotics are the standard of care for anyone afflicted with gastritis – and stomach cancer has been significantly reduced in the Western world.