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.
Tapping into the Power of the Placebo Effect
When Wayne Jonas was in medical school 40 years ago, doctors would write out a prescription for placebos, spelling it out backwards in capital letters, O-B-E-C-A-L-P. The pharmacist would fill the prescription with a sugar pill, recalls Jonas, now director of integrative health programs at the Samueli Foundation. It fulfilled the patient's desire for the doctor to do something when perhaps no drug could help, and the sugar pills did no harm.
Today, that deception is seen as unethical. But time and time again, studies have shown that placebos can have real benefits. Now, researchers are trying to untangle the mysteries of placebo effect in an effort to better treat patients.
The use of placebos took off in the post-WWII period, when randomized controlled clinical trials became the gold standard for medical research. One group in a study would be treated with a placebo, a supposedly inert pill or procedure that would not affect normal healing and recovery, while another group in the study would receive an "active" component, most commonly a pill under investigation. Presumably, the group receiving the active treatment would have a better response and the difference from the placebo group would represent the efficacy of the drug being tested. That was the basis for drug approval by the U.S. Food and Drug Administration.
"Placebo responses were marginalized," says Ted Kaptchuk, director of the Program in Placebo Studies & Therapeutic Encounters at Harvard Medical School. "Doctors were taught they have to overcome it when they were thinking about using an effective drug."
But that began to change around the turn of the 21st century. The National Institutes of Health held a series of meetings to set a research agenda and fund studies to answer some basic questions, led by Jonas who was in charge of the office of alternative medicine at the time. "People spontaneously get better all the time," says Kaptchuk. The crucial question was, is the placebo effect real? Is it more than just spontaneous healing?
Brain mechanisms
A turning point came in 2001 in a paper in Science that showed physical evidence of the placebo effect. It used positron emission tomography (PET) scans to measure release patterns of dopamine — a chemical messenger involved in how we feel pleasure — in the brains of patients with Parkinson's disease. Surprisingly, the placebo activated the same patterns that were activated by Parkinson's drugs, such as levodopa. It proved the placebo effect was real; now the search was on to better understand and control it.
A key part of the effect can be the beliefs, expectations, context, and "rituals" of the encounter between doctor and patient. Belief by the doctor and patient that the treatment would work, and the formalized practices of administering the treatment can all contribute to a positive outcome.
Conditioning can be another important component in generating a response, as Pavlov demonstrated more than a century ago in his experiments with dogs. They were trained with a bell prior to feeding such that they would begin to salivate in anticipation at the sound of a bell even with no food present.
Translating that to humans, studies with pain medications and sleeping aids showed that patients who had a positive response with a certain dose of those medications could have the same response if the doses was reduced and a dummy pill substituted, even to the point where there was no longer any active ingredient.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders.
Those types of studies troubled Kaptchuk because they often relied on deception; patients weren't told they were receiving a placebo, or at best there was a possibility that they might be randomized to receive a placebo. He believed the placebo effect could work even if patients were told upfront that they were going to receive a placebo. More than a dozen so call "open-label placebo" studies across numerous medical conditions, by Kaptchuk and others, have shown that you don't have to lie to patients for a placebo to work.
Jonas likes to tell the story of a patient who used methotrexate, a potent immunosuppressant, to control her rheumatoid arthritis. She was planning a long trip and didn't want to be bothered with the injections and monitoring required in using the drug, So she began to drink a powerful herbal extract of anise, a licorice flavor that she hated, prior to each injection. She reduced the amount of methotrexate over a period of months and finally stopped, but continued to drink the anise. That process had conditioned her body "to alter her immune function and her autoimmunity" as if she were taking the drug, much like Pavlov's dogs had been trained. She has not taken methotrexate for more than a year.
An intriguing paper published in May 2021 found that mild, non-invasive electric stimulation to the brain could not only boost the placebo effect on pain but also reduce the "nocebo" effect — when patients report a negative effect to a sham treatment. While the work is very preliminary, it may open the door to directly manipulating these responses.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders, areas where drugs often are of little help. Still, placebos aren't a cure and only a portion of patients experience a placebo effect.
Nocebo
If medicine were a soap opera, the nocebo would be the evil twin of the placebo. It's what happens when patients have adverse side effects because of the expectation that they will. It's commonly seem when patients claims to experience pain or gastric distress that can occur with a drug even when they've received a placebo. The side effects were either imagined or caused by something else.
"Up to 97% of reported pharmaceutical side effects are not caused by the drug itself but rather by nocebo effects and symptom misattribution," according to one 2019 paper.
One way to reduce a nocebo response is to simply not tell patients that specific side effects might occur. An example is a liver biopsy, in which a large-gauge needle is used to extract a tissue sample for examination. Those told ahead of time that they might experience some pain were more likely to report pain and greater pain than those who weren't offered this information.
Interestingly, a nocebo response plays out in the hippocampus, a part of the brain that is never activated in a placebo response. "I think what we are dealing with with nocebo is anxiety," says Kaptchuk, but he acknowledges that others disagree.
Distraction may be another way to minimize the nocebo effect. Pediatricians are using virtual reality (VR) to engage children and distract them during routine procedures such as blood draws and changing wound dressings, and burn patients of all ages have found relief with specially created VRs.
Treatment response
Jonas argues that what we commonly call the placebo effect is misnamed and leading us astray. "The fact is people heal and that inherent healing capacity is both powerful and influenced by mental, social, and contextual factors that are embedded in every medical encounter since the idea of treatment began," he wrote in a 2019 article in the journal Frontiers in Psychiatry. "Our understanding of healing and ability to enhance it will be accelerated if we stop using the term 'placebo response' and call it what it is—the meaning response, and its special application in medicine called the healing response."
He cites evidence that "only 15% to 20% of the healing of an individual or a population comes from health care. The rest—nearly 80%—comes from other factors rarely addressed in the health care system: behavioral and lifestyle choices that people make in their daily life."
To better align treatments and maximize their effectiveness, Jonas has created HOPE (Healing Oriented Practices & Environments) Note, "a patient-guided process designed to identify the patient's values and goals in their life and for healing." Essentially, it seeks to make clear to both doctor and patient what the patient's goals are in seeking treatment. In an extreme example of terminal cancer, some patients may choose to extend life despite the often brutal treatments, while others might prefer to optimize quality of life in the remaining time that they have. It builds on practices already taught in medical schools. Jonas believes doctors and patients can use tools like these to maximize the treatment response and achieve better outcomes.
Much of the medical profession has been resistant to these approaches. Part of that is simply tradition and limited data on their effectiveness, but another very real factor is the billing process for how they are reimbursed. Jonas says a new medical billing code added this year gives doctors another way to be compensated for the extra time and effort that a more holistic approach to medicine may initially require. Other moves away from fee-for-service payments to bundling and payment for outcomes, and the integrated care provided by the Veterans Affairs, Kaiser Permanente and other groups offer longer term hope for the future of approaches that might enhance the healing response.
This article was first published by Leaps.org on July 7, 2021.
New tech helps people of all ages stay social
In March, Sonja Bauman, 39, used an online platform called Papa, which offers “family on demand,” to meet Mariela Florez, an 83-year-old retiree. Despite living with her adult children, Florez was bored and lonely when they left for work, and her recoveries from a stroke and broken hip were going slowly. That's when Bauman began visiting twice per week. They take walks, strengthening Florez’s hip, and play games like Connect Four for mental stimulation. “It’s very important for me so I don’t feel lonely all day long,” said Florez. Her memories, blurred by the stroke, are gradually returning.
Papa is one of a growing number of tech approaches that are bringing together people of all ages. In addition to platforms like Papa that connect people in real life, other startups use virtual reality and video, with some of them focusing especially on deepening social connections between the generations — relationships that support the health of older and younger people alike. “I enjoy seeing Mariela as much as she enjoys seeing me,” Bauman said.
Connecting in real life
Telehealth expert Andrew Parker founded Papa in 2017 to improve the health outcomes of older adults and families. Seniors can meet people — some their grandkids’ age — for healthy activities, while working parents find retirees to watch their children. These “Papa Pals” are provided as a benefit through Medicare, Medicaid and some employer health plans.
In 2020, Papa connected Bauman, the 39-year-old Floridian, with another woman in her mid-70s who lives alone and has very limited mobility. Bauman began driving her to doctor’s appointments and helping her with chores around the house. “When I’m not there, she doesn’t leave her apartment,” said Bauman. The two have gone to the gym together, and they walk slowly through the neighborhood, chatting so it feels less like exercise.
Parker was driven to start Papa by the problem of social isolation among seniors, exacerbated by the pandemic, but he believes users of all ages can benefit. “Many of our Pals feel more comfortable opening up with older members than their same-aged friends,” he said.
Other platforms aim for similar, in-person connections. Generation Tech unites teens with seniors for technology training. And Mon Ami, which provides case management software for aging and disability service providers, has an app that connects isolated older people with college-age volunteers.
Making new connections through video
Several new sites match you with strangers for real-time video chatting on various topics, such as finding common ground on political issues. Other video platforms focus on intergenerational connections.
S. Jay Olshansky, a gerontology professor at the University of Illinois-Chicago, recalls the first time he saw Hyunseung Lee, an 11-year-old from Seoul, through his computer screen. The kid was shy, but Olshansky, 67, encouraged him to ask questions. “Turns out, he was thirsting for this kind of interaction.”
They’d connected through Eldera, a platform that pairs mentors age 60 and up with mentees, using an algorithm, for video conversations. “The time and wisdom of older adults is the most important natural resource we can give future generations,” said Dana Griffin, Eldera's CEO. “Connecting through a screen is the opposite of social media.”
In weekly meetings, Olshansky noticed Lee’s unique interest in math. “There’s something special in you,” Olshansky told him. “How do we bring it to the surface?” He suggested Lee write a book on his favorite subject, and the preteen ran with it, cranking out 70 pages in two weeks. Lee has published his love letter to theorems on Amazon.
Hyunseung Lee, age 11, of Korea, and U.S. college professor Jay Olshanksy, 67, discuss math, strategy and Hyunsung's budding career as a book author during their video chats through a platform called Eldera. (Photo by Dana Palmer/Eldera)
Lee’s parents told Olshansky that their son has become more assertive — a recurring theme, Griffin said. “Confidence is the number one thing parents tell us about.” Since Eldera’s inception last year, the number of mentors has grown exponentially. Even so, Griffin said the waitlist for mentors typically numbers 200 kids.
Another site, Big and Mini, hosts video interactions between seniors and young adults; about 10,000 active users have joined since 2019, said co-founder Aditi Merchant.
Users often bring the benefits of their video interactions to their real-world relationships. Olshansky views Lee as an older version of his grandkids. “Eldera teaches me how to interact with them.” Lee, high on confidence, began instructing his classmates in math. Griffin noted that a group of Eldera mentors in Memphis, who met initially on Eldera, now take walks together in-person to trade ideas for helping each other’s Eldera kids solve problems in their schools and communities.
“We’ve evolved into a community for older adults who want to give back to the world,” said Griffin. Other new tools for connection take the form of virtual reality apps.
Connecting in virtual reality
During pandemic isolation, record numbers of people bought devices for virtual and augmented reality. Such gadgets can convince you that you’re hanging out with friends, even if they’re in another hemisphere. Lifelike simulations from miles away could be especially useful for meaningful interactions between people of different generations, since they’re often geographically segregated.
VR’s benefits require further study, but users report less social isolation and depression, according to MIT research. The immersive, 3-D experience is more compelling than FaceTime or Zoom. “It’s like the difference between a phone call and video call,” said Rick Robinson, Vice President of AARP’s Innovation Labs.
“When VR is designed right, the medium disappears,” said Jeremy Bailenson of Stanford.
Dana Pierce, a 56-year-old government employee in Indiana, got Meta's VR headset in May, 2021, thinking she’d enjoy it more than a new laptop. After many virtual group tours of exotic destinations, she has no regrets. Her adventures occur on Alcove, an app made by Robinson’s Innovation Labs. He co-created it with VR-company Rendever and sought input from people over age 50 to tailor it to their interests. “I’m an introvert,” said Pierce. “I’ve been more socially active since getting my headset than I am in real life.”
Tagging along with her to places like Paris are avatars representing real people around the world. She’s gotten to know VR users in their 70s, 80s and 90s, as well as younger people and some her own age. One is a new friend she plays chess with in relaxing nature settings. Another is her oldest son. He lives 90 minutes away but, earlier this year, Pierce welcomed him and his girlfriend to her virtual house on Alcove. They chatted in the living room decorated with family photos uploaded by Pierce. Then they took out a boat to go VR fishing — because why not — until 2 a.m.
“When VR is designed right, the medium disappears,” said Jeremy Bailenson, a communications professor who directs Stanford’s Virtual Human Interaction Lab. He’s teaching a class of 175 students entirely in VR. After months of covid isolation, the first time the class met, “there was a big catharsis. It really feels like you’re in a big crowd.” Like-minded people meet in VR for events such as comedy shows and creative writing meetups, while the Swedish pop group ABBA has performed this year as digital versions of themselves (“ABBA-tars”) during a virtual concert tour.
Karen Fingerman, a psychologist and director of the Texas Aging and Longevity Center at the University of Texas-Austin, supports the idea of VR for social connection, though she added that some people need it more than others. Hospitals and assisted-living facilities are using products such as Penumbra’s REAL I-Series and MyndVR to bring VR excursions to isolated patients and seniors. “If you’re in a bed or facility, this gives you something to talk about,” said Gita Barry, Penumbra’s executive vice president.
Pierce uses it on most days. She may see another adult son, who lives with her, less often as a result. But VR helps her manage real-world stressors, more than escaping them. After a long workday, she visits her back porch on Alcove, which overlooks a pond. “It’s my little retreat,” she said. “VR improves my mood. It’s added a lot to my life.”
Some seniors are using more than one technology. Olshansky and Lee discuss strategy while playing Internet chess. And Olshansky recently began using VR. He sees his sister, who lives far away, in a virtual beach house. “It’d be a great way to interact with Hyunseung,” he said. “I should get him a headset.”
A version of this article first appeared in The Washington Post on December 3, 2021.