(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.
Laika, a gene-edited pig, was named in honor of the first living creature to orbit the earth, a stray dog named Laika.
Untold numbers of animals have contributed to science, in ways big and small. Studying cows and cowpox helped English doctor Edward Jenner create a smallpox vaccine; Ivan Pavlov's experiments on dogs' reactions to external stimuli heavily influenced modern behavioral psychology.
We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
Scientists still work with rats, rabbits, and other mammals to test cosmetics and pharmaceuticals and to conduct infectious disease research. Most of these animals remain nameless and unknown to the public, but over the years, certain individuals have had an outsize effect. We have these five animals to thank for some of our most important scientific advancements, from space travel to better organ replacement options.
1) LAIKA THE DOG
Laika was the first living creature ever to orbit the Earth. In October 1957, the Soviet Sputnik I ship had made history as the first man-made object sent into Earth's orbit; Premier Nikita Khrushchev was keen to gain another Space Race victory by sending up a canine cosmonaut.
Laika ("barker" in Russian), was a stray dog, reportedly a husky-spitz mix, recruited among several other female strays for the trip. Although the scientists put extensive work into preparing Laika and the other canine finalists—evaluating their reactions to air-pressure variations, training them to adapt to pelvic sanitation devices meant to contain waste, and eventually having them live in pressurized capsules for weeks—there was no expectation that the dog would return to Earth, and only one meal's worth of food was sent up with her.
Sputnik II, six times heavier than its predecessor, launched on November 3, 1957. Soviet broadcasts reported that Laika, fitted out with surgically implanted devices to monitor her heart rate, blood pressure, and breathing rates, survived until November 12; the spacecraft stayed in orbit for five more months, burning up when it re-entered the atmosphere.
At the time, the Sputnik II team reassured the world that Laika had died painlessly of oxygen deprivation. It was only decades later, in the 1990s, that Oleg Gazenko—one of the scientists and dog trainers assigned to the mission—revealed that Laika had died 5 to 7 hours after launch from a combination of heat and stress. The capsule had overheated, probably as a result of the rushed preparation; after the fourth orbit, the temperature inside Sputnik was over 90 degrees, and it's doubtful she could have survived much past that. "The more time passes, the more I'm sorry about it. We shouldn't have done it," Gazenko said. "We did not learn enough from the mission to justify the death of the dog."
Yet even the four or five orbits that Laika did complete were enough to spur scientists to press on in the effort to send a human into space.
2) HAM THE CHIMP
Four years after Laika's ill-fated flight, a chimpanzee named Ham entered suborbital flight in the American Project Mercury MR-2 mission on January 31, 1961, becoming the first hominid in space—and unlike Laika, he returned to Earth, alive, after a 16-minute flight.
Even though Ham's flight was not destined for orbit, the spacecraft and booster used on his trip were the same combination intended for the first (human) American's trip later that year. If he came back unharmed, NASA's medical team would be prepared to okay astronaut Alan Shepard's flight.
For approximately 18 months before liftoff, Ham was trained to perform simple tasks, like pushing levers, in response to visual and auditory cues. (If he failed, he received an electric shock; correct performance earned him a treat. Pavlov would have been pleased.)
At 37 pounds, Ham was also the heaviest animal to ever make it to space. His vital signs and movements were monitored from Earth, and after a light electric shock from the ground team reminded him of his tasks, he performed his lever-pushing just a bit slower than he had on Earth, verifying that motion would not be seriously impaired in space.
Less than three months after Ham returned to Earth, on April 12, 1961, Soviet cosmonaut Yuri Gagarin became the first human to complete an orbital flight; Shepard was close behind, successfully crewing the MR-3 mission on May 5. For his part, Ham "retired" to the National Zoo in Washington D.C. for 17 years, before being transferred to the North Carolina Zoological Park; he died of liver failure in 1983 at age 26. His grave is at the International Space Hall of Fame in New Mexico.
3) KOKO THE GORILLA
A western lowland gorilla born at the San Francisco Zoo, Hanabi-ko, or "Koko," became famous in the 1970s for her cognitive and communicative abilities. Psychologist Francine "Penny" Patterson, then a doctoral student at Stanford, chose Koko to work on a language research project, teaching her American Sign Language; by age four, Koko demonstrated the ability both to make up new words and to combine known words to express herself creatively, as opposed to simply mimicking her trainer.
Koko's work with Patterson reflected levels of cognition that were higher than non-human primates had previously been thought to have; by the end of her life, her language skills were roughly equivalent to a young child's, with a vocabulary of around 1,000 signs and the ability to understand 2,000 words of spoken English.
An especially impactful study in 2012 showed that Koko had learned to play the recorder, revealing an ability for voluntary breath control that scientists had previously thought was linked closely to speech and could only be developed by humans. Barbara J. King, a biological anthropologist, suggested that Koko's immersion in a human environment may have helped her develop such a skill, and that it might be misleading to consider similar abilities "innate" or lacking in either humans or non-human primates.
Koko's displays of emotions also fascinated the public, especially those that seemed to closely mirror humans': she cared for pet kittens; appeared on Mr. Rogers' Neighborhood and untied the host's shoes for him; acted playfully with Robin Williams during a visit from him, and later expressed grief when told about the comedian's death. Koko died in her sleep in June 2018, at age 46. Patterson continues to run The Gorilla Foundation, which is dedicated to using inter-species communication to motivate conservation efforts.
4) DOLLY THE SHEEP
Dolly—named after country singer Dolly Parton—was the first mammal ever to be cloned from an adult somatic cell, using the process of nuclear transfer. She was born in 1996 as part of research by scientists Keith Campbell and Ian Wilmut of the University of Edinburgh.
By taking a donor cell from an adult sheep's mammary gland, using it to replace the cell nucleus of an unfertilized, developing egg cell, and then bringing the resultant embryo to term, Campbell and Wilmut proved that even a mature cell (one that had developed to perform mammary gland functions) could revert to an embryonic state and go on to develop into any and all parts of a mammal.
Although cloned livestock are legal in the U.S.—the FDA approved the practice in 2008, after determining that there was no difference between the meat and milk of cattle, pigs, and goats—Dolly has had an even bigger impact on stem cell research. The successful test of nuclear transfer proved that it was possible to change a cell's gene expression by changing its nucleus.
Japanese stem cell biologist Shinya Yamanaka, inspired by the birth of Dolly, won the Nobel Prize in 2012 for his adaptation of the technique. He developed induced pluripotent stem cells (iPS cells) by chemically reverting mature cells back to an embryonic-like blank state that is highly desirable for disease research and treatment. This technique allows researchers to work with such stem cells without the ethically charged complication of having to destroy a human embryo in the process.
5) LAIKA THE PIG
Named in honor of the dog who made it to space, the second science-famous Laika was a genetically engineered pig born in China in 2015 as a result of gene editing carried out by Cambridge, MA startup eGenesis and collaborators.* eGenesis aims to create pigs whose organs—hearts, kidneys, lungs, and more—are safe to transplant into people.
Using animal organs in humans (xenotransplantation) is tricky: the immune system is very good at recognizing interlopers, and the human body can start to reject an organ from another species in as little as five minutes. But pigs are otherwise exceptionally good potential donors for humans: their organs' sizes and functions are very similar, and their quick gestation and maturation make them attractive from an efficiency standpoint, given that twenty Americans die every day waiting for organ donors.
Perhaps unsurprisingly, Dolly the sheep helped move xenotransplantation forward. In the 1990s, immunologist David Sachs was able to use a similar cloning method to eliminate alpha-gal, an enzyme that is produced by most animals with immune systems, including pigs—but not humans. Since our immune systems don't recognize alpha-gal, attacks on that enzyme are a major cause of organ rejection. Sachs' experiments increased the survival time of pig organs in primates to weeks: a huge improvement, but not nearly enough for someone in need of a liver or heart.
The advent of CRISPR technology, and the ability to edit genes, has allowed another leap. In 2015, researchers at eGenesis used targeted gene-editing to eliminate the genes for porcine endogenous retroviruses from pig kidney cells. These viral elements are part of all pigs' genomes and pose a potentially high risk of infecting human cells. (After the HIV/AIDS crisis especially, there was a lot of anxiety about potentially introducing a new virus into the human population.)
The eGenesis lab used nuclear transfer to embed the edited nuclei into egg cells taken from a normal pig; and Laika was born months later—without the dangerous viral genes. eGenesis is now working to make the organs even more humanlike, with the goal of one day providing organs to every human patient in need.
*[Disclosure: In 2019, eGenesis received a series B investment from Leaps By Bayer, the funding sponsor of leapsmag. However, leapsmag is editorially independent of Bayer and is under no obligation to cover companies they invest in.]
[Correction, March 3, 2020: Laika the gene-edited pig was born in China, not Cambridge, and eGenesis is pursuing xenotransplant programs that include heart, kidney, and lung, but not skin, as originally written.]
