(Left to right) Vickie Naylor, Bernadine Clay, and Donna Maxey read a memory prompt as they take part in the Sharing History through Active Reminiscence and Photo-Imagery (SHARP) study, September 20, 2017.
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.
The Northern white rhinoceros Nola, the last one in the U.S. at that time in 2015, pictured here with author Jeanne Loring and Oliver Ryder (in truck), with a film crew and keepers in the San Diego Zoo's savanna. Nola sadly passed away that year.
Because of human activities that destroy habitats, creatures are now becoming extinct at a rate that is higher than any previously experienced. Some animals, like the giant panda and the California condor, have been pulled back from the brink of extinction by conserving their habitats, breeding in captivity, and educating the public about their plight.
But not the northern white rhino. This gentle giant is a vegetarian that can weigh up to 5,000 pounds. The rhino's weakness is its horn, which has become a valuable commodity because of the mistaken idea that it grants power and has medicinal value. Horns are not medicine; the horns are made of keratin, the same protein that is in fingernails. But as recently as 2017 more than 1,000 rhinos were slaughtered each year to harvest their horns.
All 6 rhino species are endangered. But the northern white has been devastated. Only two members of this species are alive now: Najin, age 32, and her daughter Fatu, 21, live in a protected park in Kenya. They are social animals and would prefer the company of other rhinos of their kind; but they can't know that they are the last two survivors of their entire species. No males exist anymore. The last male, Sudan, died in 2018 at age 45.
We are celebrating a huge milestone in the efforts to use stem cells to rescue the rhino.
I became involved in the rhino rescue project on a sunny day in February, 2008 at the San Diego Wild Animal Park in Escondido, about 30 miles north of my lab in La Jolla. My lab had relocated a couple of months earlier to Scripps Research Institute to start the Center for Regenerative Medicine for human stem cell research. To thank my staff for their hard work, I wanted to arrange a special treat. I contacted my friend Oliver Ryder, who is director of the Institute for Conservation Research at the zoo, to see if I could take them on a safari, a tour in a truck through the savanna habitat at the park.
This was the first of the "stem cell safaris" that the lab would enjoy over the next few years. On the safari we saw elands and cape buffalo, and fed giraffes and rhinos. And we talked about stem cells; in particular, we discussed a surprising technological breakthrough recently reported by the Japanese scientist Shinya Yamanaka that enabled conversion of ordinary skin cells into pluripotent stem cells.
Pluripotent stem cells can develop into virtually any cell type in the body. They exist when we are very young embryos; five days after we were just fertilized eggs, we became blastocysts, invisible tiny balls of a few hundred cells packed with the power to develop into an entire human being. Long before we are born, these cells of vast potential transform into highly specialized cells that generate our brains, our hearts, and everything else.
Human pluripotent stem cells from blastocysts can be cultured in the lab, and are called embryonic stem cells. But thanks to Dr. Yamanaka, anyone can have their skin cells reprogrammed into pluripotent stem cells, just like the ones we had when we were embryos. Dr. Yamanaka won the Nobel Prize for these cells, called "induced pluripotent stem cells" (iPSCs) several years later.
On our safari we realized that if we could make these reprogrammed stem cells from human skin cells, why couldn't we make them from animals' cells? How about endangered animals? Could such stem cells be made from animals whose skin cells had been being preserved since the 1970s in the San Diego Zoo's Frozen Zoo®? Our safari leader, Oliver Ryder, was the curator of the Frozen Zoo and knew what animal cells were stored in its giant liquid nitrogen tanks at −196°C (-320° F). The Frozen Zoo was established by Dr. Kurt Benirschke in 1975 in the hope that someday the collection would aid in rescue of animals that were on the brink of extinction. The frozen collection reached 10,000 cell lines this year.
We returned to the lab after the safari, and I asked my scientists if any of them would like to take on the challenge of making reprogrammed stem cells from endangered species. My new postdoctoral fellow, Inbar Friedrich Ben-Nun, raised her hand. Inbar had arrived only a few weeks earlier from Israel, and she was excited about doing something that had never been done before. Oliver picked the animals we would use. He chose his favorite animal, the critically endangered northern white rhinoceros, and the drill, which is an endangered primate related to the mandrill monkey,
When Inbar started work on reprogramming cells from the Frozen Zoo, there were 8 living northern rhinoceros around the world: Nola, Angalifu, Nesari, Nabire, Suni, Sudan, Najin, and Fatu. We chose to reprogram Fatu, the youngest of the remaining animals.
Through sheer determination and trial and error, Inbar got the reprogramming technique to work, and in 2011 we published the first report of iPSCs from endangered species in the scientific journal Nature Methods. The cover of the journal featured a drawing of an ark packed with animals that might someday be rescued through iPSC technology. By 2011, one of the 8 rhinos, Nesari, had died.
This kernel of hope for using iPSCs to rescue rhinos grew over the next 10 years. The zoo built the Rhino Rescue Center, and brought in 6 females of the closely related species, the southern white rhinoceros, from Africa. Southern white rhino populations are on the rise, and it appears that this species will survive, at least in captivity. The females are destined to be surrogate mothers for embryos made from northern white rhino cells, when eventually we hope to generate sperm and eggs from the reprogrammed stem cells, and fertilize the eggs in vitro, much the same as human IVF.
The author, Jeanne Loring, at the Rhino Rescue Center with one of the southern white rhino surrogates.
David Barker
As this project has progressed, we've been saddened by the loss of all but the last two remaining members of the species. Nola, the last northern white rhino in the U.S., who was at the San Diego Zoo, died in 2015.
But we are celebrating a huge milestone in the efforts to use stem cells to rescue the rhino. Just over a month ago, we reported that by reprogramming cells preserved in the Frozen Zoo, we produced iPSCs from stored cells of 9 northern white rhinos: Fatu, Najin, Nola, Suni, Nadi, Dinka, Nasima, Saut, and Angalifu. We also reprogrammed cells from two of the southern white females, Amani and Wallis.
We don't know when it will be possible to make a northern white rhino embryo; we have to figure out how to use methods already developed for laboratory mice to generate sperm and eggs from these cells. The male rhino Angalifu died in 2014, but ever since I saw beating heart cells derived from his very own cells in a culture dish, I've felt hope that he will one day have children who will seed a thriving new herd of northern white rhinos.
