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.
Scientists Are Studying How to Help Dogs Have Longer Lives, in a Bid to Further Our Own
The sad eyes. The wagging tail. The frustrated whine. The excited bark. Dogs know how to get their owners to fork over the food more often.
The extra calories dogs get from feeding patterns now used by many Americans may not be good for them from a health and longevity viewpoint. In research from a large study called the Dog Aging Project, canines fed once a day had better scores on cognition tests and lower odds of developing diseases of organs throughout the body: intestinal tract, mouth and teeth, bones and joints, kidneys and bladder, and liver and pancreas.
Fewer than 1 in 10 dog owners fed their furry friends once daily, while nearly three fourths provided two daily meals.
“Most veterinarians have been led to believe that feeding dogs twice a day is optimal, but this is a relatively new idea that has developed over the past few decades with little supportive evidence from a health standpoint,” said Matt Kaeberlein, PhD, Co-Director of the Dog Aging Project, a professor of pathology and Director of the Healthy Aging and Longevity Research Institute at the University of Washington. Kaeberlein studies basic mechanisms of aging to find ways of extending the healthspan, the number of years of life lived free of disease. It’s not enough to extend the lifespan unless declines in biological function and risks of age-related diseases are also studied, he believes, hence the healthspan.
The Dog Aging Project is studying tens of thousands of dogs living with their owners in the real world, not a biology laboratory. The feeding study is the first of several reports now coming from the project based on owners’ annual reports of demographics, physical activity, environment, dog behavior, diet, medications and supplements, and health status. It has been posted on bioRxiv as it goes through peer review.
“All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans. It just happens much faster in dogs.”
“The Dog Aging Project is one of the most exciting in the longevity space,” said David A. Sinclair, professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. “Not only is it important to help our companions live longer and healthier, but because they are like people and share the same environment and many of the lifestyles as their owners, they are the perfect model for human longevity interventions.”
The epigenetic clock — and specifically changes in gene expression resulting from methylation of cytosine and guanine in the DNA — provides the critical connection between aging in dogs and people. “All available evidence suggests that most biological mechanisms of aging in dogs will be conserved in humans,” Kaeberlein said. “It just happens much faster in dogs.” These methylation changes, called the “methylomes,” have been associated with rates of aging in dogs, humans, and also mice.
In a 2020 study young dogs matched with young adults and aged dogs matched with older adults showed the greatest similarities in methylomes. In the Cell Systems report, Tina Wang of the University of California, San Diego, and colleagues wrote that the methylome “can be used to quantitatively translate the age-related physiology experienced by one organism (i.e., a model species like dog) to the age at which physiology in a second organism is most similar (i.e., a second model or humans).” This allows rates of aging in one species to be mapped onto aging in another species, providing “a compelling tool in the quest to understand aging and identify interventions for maximizing healthy lifespan.”
In the Dog Aging Project study, 8% of 24,238 owners fed their dogs once daily, the same as the percentage of owners serving three daily meals. Twice-daily feedings were most common (73%), and just over 1 in 10 owners (11%) “free fed” their dogs by just filling up the bowl whenever it was empty — most likely Rover’s favorite option.
“The notion of breakfast, lunch, and dinner for people in the United States is not based on large studies that compared three meals a day to two meals a day, or to four, “ said Kate E. Creevy, chief veterinary officer with the Dog Aging Project and associate professor at Texas A&M University. “It’s more about what we are accustomed to. Similarly, there are not large population studies comparing outcomes of dogs fed once, twice, or three times a day.”
“We do not recommend that people change their dogs’ diets based on this report,” Creevy emphasized. “It’s important to understand the difference between research that finds associations versus research that finds cause and effect.”
To establish cause and effect, the Dog Aging Project will follow their cohort over many years. Then, Creevy said, “We will be able to determine whether the associations we have found with feeding frequency are causes, or effects, or neither.”
While not yet actionable, the feeding findings fit with biology across a variety of animals, Kaeberlein said, including indicators that better health translates into longer healthspans. He said that caloric restriction and perhaps time-restricted eating or intermittent fasting — all ways that some human diets are structured — can have a positive impact on the biology of aging by allowing the gastrointestinal tract to have time each day to rest and repair itself, just as sleep benefits the brain through rest.
Timing of meals is also related to the concept of ketogenesis, Kaeberlein explained. Without access to glucose, animals switch over to a ketogenic state in which back-up systems produce energy through metabolic pathways that generate ketones. Mice go into this state very quickly, after a few hours or an overnight fast, while people shift to ketogenesis more slowly, from a few hours to up to 36 hours for people on typical Western diets, Kaeberlein said.
Dogs are different. They take at least two days to shift to ketogenesis, suggesting they have evolved to need fewer meals that are spaced out rather than the multiple daily meals plus snacks that people prefer.
As this relates to longevity, Kaeberlein said that a couple of studies show that mice who are fed a ketogenic diet have longer lifespans (years of life regardless of health). “For us, the next step is to analyze the composition of the dogs’ diets or the relationship of multiple daily feedings with obesity,” he said. “Maybe not being obese is related to better health.”
To learn more, the Dog Aging Project needs dogs — lots of dogs! Kaeberlein wants at least 100,000 dogs, including small dogs, large dogs, dogs of all ages. Puppies are needed for the researchers to follow across their lifespan. The project has an excellent website where owners can volunteer to participate.
Nutritional strategies are often not built around sound scientific principles, Kaeberlein said. In human nutrition, people have tried all kinds of diets over the years, including some that were completely wrong. Kaeberlein and his colleagues in the Dog Aging Project want to change that, at least for people’s canine companions, and hopefully, as a result, give dogs added years of healthy life and provide clues for human nutrition.
After that, maybe they can do something about those sad eyes and the frustrated whine.
Podcast: New Solutions to Combat Gluten Sensitivities and Food Allergies
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
This month, we talk Anat Binur, the CEO of Israeli/U.S.-based biotech company Ukko. Ukko is taking a revolutionary approach to the distressing problem of food allergies and gluten sensitivities: their scientists are designing and engineering proteins that keep the good biophysical properties of the original proteins, while removing the immune-triggering parts that can cause life-threatening allergies. The end goal is proteins that are safe for everyone. Ukko is focusing first on developing a new safe gluten protein for use in baking and a new peanut protein for use as a therapeutic. Their unique platform could theoretically be used for any protein-based allergy, including cats and bees. Hear more in this episode.
Watch the 60-second trailer
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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.