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.
Is a Successful HIV Vaccine Finally on the Horizon?
Few vaccines have been as complicated—and filled with false starts and crushed hopes—as the development of an HIV vaccine.
While antivirals help HIV-positive patients live longer and reduce viral transmission to virtually nil, these medications must be taken for life, and preventative medications like pre-exposure prophylaxis, known as PrEP, need to be taken every day to be effective. Vaccines, even if they need boosters, would make prevention much easier.
In August, Moderna began human trials for two HIV vaccine candidates based on messenger RNA.
As they have with the Covid-19 pandemic, mRNA vaccines could change the game. The technology could be applied for gene editing therapy, cancer, other infectious diseases—even a universal influenza vaccine.
In the past, three other mRNA vaccines completed phase-2 trials without success. But the easily customizable platforms mean the vaccines can be tweaked better to target HIV as researchers learn more.
Ever since HIV was discovered as the virus causing AIDS, researchers have been searching for a vaccine. But the decades-long journey has so far been fruitless; while some vaccine candidates showed promise in early trials, none of them have worked well among later-stage clinical trials.
There are two main reasons for this: HIV evolves incredibly quickly, and the structure of the virus makes it very difficult to neutralize with antibodies.
"We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
"You know the panic that goes on when a new coronavirus variant surfaces?" asked John Moore, professor of microbiology and immunology at Weill Cornell Medicine who has researched HIV vaccines for 25 years. "With HIV, that kind of variation [happens] pretty much every day in everybody who's infected. It's just orders of magnitude more variable a virus."
Vaccines like these usually work by imitating the outer layer of a virus to teach cells how to recognize and fight off the real thing off before it enters the cell. "If you can prevent landing, you can essentially keep the virus out of the cell," said Larry Corey, the former president and director of the Fred Hutchinson Cancer Research Center who helped run a recent trial of a Johnson & Johnson HIV vaccine candidate, which failed its first efficacy trial.
Like the coronavirus, HIV also has a spike protein with a receptor-binding domain—what Moore calls "the notorious RBD"—that could be neutralized with antibodies. But while that target sticks out like a sore thumb in a virus like SARS-CoV-2, in HIV it's buried under a dense shield. That's not the only target for neutralizing the virus, but all of the targets evolve rapidly and are difficult to reach.
"We understand these targets. We know where they are. But it's still proving incredibly difficult to raise antibodies against them by vaccination," Moore said.
In fact, mRNA vaccines for HIV have been under development for years. The Covid vaccines were built on decades of that research. But it's not as simple as building on this momentum, because of how much more complicated HIV is than SARS-CoV-2, researchers said.
"They haven't succeeded because they were not designed appropriately and haven't been able to induce what is necessary for them to induce," Moore said. "The mRNA technology will enable you to produce a lot of antibodies to the HIV envelope, but if they're the wrong antibodies that doesn't solve the problem."
Part of the problem is that the HIV vaccines have to perform better than our own immune systems. Many vaccines are created by imitating how our bodies overcome an infection, but that doesn't happen with HIV. Once you have the virus, you can't fight it off on your own.
"The human immune system actually does not know how to innately cure HIV," Corey said. "We needed to improve upon the human immune system to make it quicker… with Covid. But we have to actually be better than the human immune system" with HIV.
But in the past few years, there have been impressive leaps in understanding how an HIV vaccine might work. Scientists have known for decades that neutralizing antibodies are key for a vaccine. But in 2010 or so, they were able to mimic the HIV spike and understand how antibodies need to disable the virus. "It helps us understand the nature of the problem, but doesn't instantly solve the problem," Moore said. "Without neutralizing antibodies, you don't have a chance."
Because the vaccines need to induce broadly neutralizing antibodies, and because it's very difficult to neutralize the highly variable HIV, any vaccine will likely be a series of shots that teach the immune system to be on the lookout for a variety of potential attacks.
"Each dose is going to have to have a different purpose," Corey said. "And we hope by the end of the third or fourth dose, we will achieve the level of neutralization that we want."
That's not ideal, because each individual component has to be made and tested—and four shots make the vaccine harder to administer.
"You wouldn't even be going down that route, if there was a better alternative," Moore said. "But there isn't a better alternative."
The mRNA platform is exciting because it is easily customizable, which is especially important in fighting against a shapeshifting, complicated virus. And the mRNA platform has shown itself, in the Covid pandemic, to be safe and quick to make. Effective Covid vaccines were comparatively easy to develop, since the coronavirus is easier to battle than HIV. But companies like Moderna are capitalizing on their success to launch other mRNA therapeutics and vaccines, including the HIV trial.
"You can make the vaccine in two months, three months, in a research lab, and not a year—and the cost of that is really less," Corey said. "It gives us a chance to try many more options, if we've got a good response."
In a trial on macaque monkeys, the Moderna vaccine reduced the chances of infection by 85 percent. "The mRNA platform represents a very promising approach for the development of an HIV vaccine in the future," said Dr. Peng Zhang, who is helping lead the trial at the National Institute of Allergy and Infectious Diseases.
Moderna's trial in humans represents "a very exciting possibility for the prevention of HIV infection," Dr. Monica Gandhi, director of the UCSF-Gladstone Center for AIDS Research, said in an email. "We in HIV medicine have been desperate to find a vaccine that has effectiveness, but this goal has been elusive so far."
If a successful HIV vaccine is developed, the series of shots could include an mRNA shot that primes the immune system, followed by protein subunits that generate the necessary antibodies, Moore said.
"I think it's the only thing that's worth doing," he said. "Without something complicated like that, you have no chance of inducing broadly neutralizing antibodies."
"I can't guarantee you that's going to work," Moore added. "It may completely fail. But at least it's got some science behind it."
New Podcast: The Lead Scientist for the NASA Mission to Venus
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, our guest is JPL's Dr. Suzanne Smrekar, who will be pushing the boundaries of knowledge about the planet Venus during the upcoming VERITAS mission set to launch in 2028. Why did Earth's twin planet develop so differently than our own? Could Venus ever have hosted life? What is the bigger purpose for humanity in studying the solar system -- is it purely scientific, or is it also a matter of art and philosophy? Hear Dr. Smrekar discuss all this and more on the latest episode.
Watch the 30-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.