Breakthroughs in Alzheimer’s Research Give Cause for Optimism

When Kathleen Mangi asked her husband how he thought her sister was doing, James Mangi grew concerned. Kathleen Mangi’s sister had died two years before. “When she asked me the same question over and over again a few minutes apart, I knew something was wrong,” recalls James Mangi, who lives in Saline, Mich. “I didn't know exactly what it was at the time, but I knew it was clearly a serious problem.”

Kathleen Mangi, a senior physical scientist at the U.S. Department of Energy, was diagnosed at 57 with early-onset Alzheimer’s disease. That was 17 years ago. Her husband, also a scientist and business owner, didn’t know what to do. “When it happens to your family, it’s a bolt out of the blue,” Mangi says.

An estimated 6.7 million Americans are living with Alzheimer’s disease, the most common form of dementia and one of the leading causes of death among people 65 and older. By 2050, an estimated 13 million Americans will have the degenerative brain disease, according to Monica Moreno, who oversees care and support efforts for the Alzheimer’s Association. One in 20 people aged 65 to 74, more than 10% of people aged 75 to 84, and one-third of people aged 85 or older have Alzheimer’s. 

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Finding a cure or even an effective treatment has been difficult. Now, after billions of dollars in research and more than 100 drug failures, advocates are celebrating breakthroughs, including drugs that for the first time treat the underlying causes of the disease. Experts are optimistic that we may be on the precipice of significant changes in how the disease is treated and potentially even prevented. 

Percy Griffin, director of scientific engagement for the Alzheimer’s Association, is hopeful about major advancements in the near future. “It’s a very exciting time for Alzheimer’s research,” Griffin says. “This is the most optimistic time in the field.” While the new treatments are useful for patients in the earliest stages of the disease, Griffin believes these advances will spur research that finds answers for patients with more advanced Alzheimer’s. “We’re by no means stopping here,” he says.

In addition to drugs that treat the underlying causes of Alzheimer's, developments include:

• Patients experiencing one of the most common and challenging symptoms, agitation, got a pharmaceutical option last year when the FDA approved the antipsychotic drug Rexulti (Brexpiprazole) for the treatment of agitation associated with dementia due to Alzheimer’s disease.
• Researchers are discovering lifestyle modifications that have a consequential impact on Alzheimer’s mitigation and management and are working to give patients detailed guidance on changes they can make.
• Blood tests may soon be available to enable routine early diagnosis, potentially even before the onset of symptoms.
• Medicare expanded access to PET scans, which aid in early and accurate diagnosis.

Eric M. Reiman, executive director of Banner Alzheimer’s Institute in Arizona, explains that delaying the onset of the disease, as some new drugs promise to do, can be extremely significant. “If you could delay the clinical onset of Alzheimer's by only five years, you could reduce the number of people who developed the disease by half because it doubles every five years,” Reiman says. “There's a chance to do even better than that.”

Along with medical advancements, attitudes toward Alzheimer’s are improving. “It is getting better,” says Mangi, who advocates for families. “Even in the time I've been vocal about it, which is the last five or six years, there has been an increase in the general awareness and the willingness of society to talk about Alzheimer’s and other dementias.” 

Challenges for patients with Alzheimer’s 

But challenges remain. While new treatments for the disease and its early stages are considered major advances, few advances are immediately seen for long-time patients.

As James Mangi sees it, the new treatments are like a fire bucket. They’re useless against a raging wildfire. But if you have a sparking campfire, that bucket of water could make all the difference in preventing tragedy. “At the very early stage, we might be able to stop it in its tracks someday,” he says.

Meanwhile, patients and family caregivers lack desperately needed financial and emotional support. Currently, the Alzheimer’s Association estimates that 11 million unpaid caregivers, including family members, provide 18 billion hours of care worth almost $340 billion a year (versus $345 billion in paid care). And these numbers are only projected to grow substantially as the population ages. With an estimated 40% of unpaid caregivers experiencing depression, the toll on society is daunting.

And while early diagnosis is key to the success of new treatments, it’s not routine. “It is uncommon for a busy primary care physician to ask about memory and thinking problems during their often, typically eight-minute visit, partly due to the misconception that there's nothing one could do about it, and partly because of the inability to provide clear answers just yet,” Reiman says. “For that reason, 60% of patients with Alzheimer's dementia never have an evaluation or a diagnosis in their lifetime.”

As Reiman describes it, the experience for many is physicians who “diagnose and adios.” Even when a patient is seen by a specialist in a memory center, the standard of care “has been more of a consultation model: Evaluate individuals for clinical severity, rule out reversible memory and thinking problems—that is other medical conditions or medications that may be contributing — perhaps offer symptomatic medication treatment.” With a diagnosis, the patient and family caregiver might be given a referral to a local chapter of the Alzheimer's Association chapter or another support group, but not much else.

“It would be helpful for patients and families to know what the course of the illness is, that they're not going to fall off a cliff, that there’s life after diagnosis of Alzheimer's or other dementias and that there are certain strategies that can help to improve the quality of life even in the absence of slowing decline,” Reiman says.

 Options for patients and families 

Reiman says patients and families should know there are treatments, including drugs that can have a small, but meaningful impact on memory and others that can mitigate the other effects of the disease.

“One of the common challenges is repeating rituals,” Reiman says. A patient might repeatedly ask, “Where's mom?” A family member typically responds by reminding the patient that their mother died, making the person anxious and relearning an unpleasant fact.

Reiman says a coping strategy is to help family members “live in the person's reality and then refocus their attention if needed.” So instead of repeating that mom died, the family member can bring up a memory about mom and engage the person in a conversation about her.

New Alzheimer’s drugs 

Griffin says there’s a “robust pipeline” of 140 different therapies being tested in clinical trials that address different aspects of how the disease attacks the brain. Since 2021, the Food and Drug Administration (FDA) has approved two drugs that, for the first time, treat an underlying cause of the disease. Monoclonal antibodies Leqembi (Lecanemab) and Aduhelm (Aducanumab), target a protein, beta-amyloid, that collects between neurons in the brain. Early clinical studies showed that Lecanemab slowed cognitive decline by as much as 27% in early Alzheimer's patients, compared to a placebo. This translated to a delay of about six months in the progression of the disease over the 18 months of the study. The FDA granted Lecanemab full approval in July.

While Aducanumab (the first of the two drugs to get accelerated FDA approval) also reduced beta-amyloid in the brain, its clinical effects were not as clear. The FDA’s approval of the drug over the objections of an advisory panel was controversial, generating a critical congressional investigation. It never received full approval from the agency and its use appears negligible.

Access to Leqembi is limited, even among early-stage patients, partly because it’s administered intravenously every other week and partly because the drug has been studied only on people who meet strict requirements, including general health and body mass index. The drug also carries serious side effects, including brain bleeding and swelling. To be covered by Medicare, the physician must participate in a qualifying registry with an appropriate clinical team and follow-up care.

Research in August 2023 concluded that just a small percentage of older adults who are in the early stages of Alzheimer’s disease meet the eligibility criteria to receive Leqembi. 

On top of that, the new drugs are expensive. Drug maker Biogen set the price of Leqembi at $26,500 a year. However, an independent nonprofit that advocates for cost-effective medical care estimated it should be sold for as little as $8,900 a year based on its effectiveness. Medicare Part B will cover Leqembi, paying for 80% of the cost for eligible beneficiaries, meaning patients would be responsible for $5,300 a year.

The long-term effects remain to be seen. Studies so far followed patients over 18 months with a disease that can last decades. As patients are prescribed the medications, ongoing clinical studies track whether the drugs continue to stave off decline and whether they pose long-term dangers.

Still, advocates say the drug breakthroughs are meaningful, beyond the specific patients who receive them and will spur further research. As Reiman describes it, “What this has meant is not only do you have clinically proven treatments and compelling evidence that amyloid aggregates like plaques are involved in the development of Alzheimer's disease, but you have now increased confidence that the same treatments if started even earlier will have a more profound benefit.”

Researchers are also studying possible vaccines that may prevent or change the course of the disease.

Other drugs being studied will address tau, a protein that develops abnormally in the brains of Alzheimer’s patients. According to the National Institute on Aging, “evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and beta-amyloid proteins and several other factors.”

A third monoclonal antibody, Donanemab, targeting beta-amyloid and tau proteins, is expected to receive an FDA nod soon. It has been shown in clinical trials to slow the progression of Alzheimer’s by 60% compared to a placebo. According to information from the Alzheimer’s Association, significant benefits were also seen in more advanced patients. 

Griffin says additional possible treatments focus on inflammation and the involvement of the brain’s immune cells in Alzheimer’s. Similar to HIV and cancer, Griffin says, Alzheimer’s may eventually be treated in all its biological aspects, with the ultimate goal being a combination therapy that also works with lifestyle changes to mitigate or avoid the disease. 

 Lifestyle changes for Alzheimer’s

Various studies have found the brain benefits from everything from sexual activity and deep sleep to exposure to certain scents to volunteering, reading and doing puzzles. Traditional healthy living, such as exercise and nutrition, as well as social engagement have also been found to benefit the aging brain. 

“Some of the most exciting research has been in the area of lifestyle modification as opposed to pharmaceuticals,” says Kristina F. Zdanys, a geriatric psychiatrist at UConn Health at the University of Connecticut. “That gives our patients a lot more control. They can be doing things actively themselves. Lifestyle modification options are empowering for the patients and can also be utilized on a broader public health level.”

Limiting alcohol and not using tobacco are two steps people can take, as well as maintaining a low-fat healthy diet and continuing to engage in social activity. 

Researchers hope to drill down on specific results for a spectrum of lifestyle changes. Griffin says a newly initiated two-year study, known as the U.S. Pointer Study will allow researchers, using 2,000 volunteers, to look at a variety of lifestyle changes and treatments in an effort to compile what amounts to a recipe book for ways to minimize the disease.

Diagnostic advances

It takes Alzheimer’s 20 years to start showing symptoms. 

The main way to diagnose Alzheimer’s now is by looking at proteins in spinal fluid. But researchers believe diagnosing and treating the disease before the onset of memory issues can be key to effective treatment, which also could lower side effects. To that end, scientists say blood tests are expected to soon be available to easily diagnose the disease earlier, potentially before symptoms appear. Yazeed S. Maghaydah, a geriatric physician at UConn Health, says new blood tests aren’t yet useful as definitive diagnosis tools. But he expects in the future they will be as reliable and easy to use as blood sugar and urine tests. And Griffin says it may be possible in the near future to diagnose Alzheimer’s with a finger-prick blood test.

In October 2023, Medicare expanded access for patients to receive PET (amyloid positron emission tomography) imaging, which helps identify evidence of Alzheimer’s in the brain. According to the Alzheimer’s Association, PET imaging enables clinicians to distinguish Alzheimer’s disease from other causes of dementia or memory loss. Until the expansion, patients were limited to coverage of one PET scan in their lifetime. Enabling more frequent use of PET imaging, Griffin says, means more people will be diagnosed earlier.

Early detection of Alzheimer’s is critically important, Moreno says, but not just to increase the success of treatment.  “We also know,” she says, “when someone goes to the doctor to get a diagnosis early, that allows the person with dementia to be part of the planning process rather than waiting for when they can’t make decisions themselves. We don’t want families to have to struggle with what decisions they would have wanted.”

While Kathleen Mangi is in hospice, her husband says she still has life. “We don’t believe that the end days are upon us,” he says, “but the transition is beginning. The main thing, that is important to me, is that she is comfortable. She is declining gracefully. I celebrate every day that she can smile back at me.”

Early signs of Alzheimer’s and dementia 

A key to effective treatment of Alzheimer’s is detecting the disease as early as possible. Ultimately, researchers hope new tests will enable routine diagnosis before symptoms, which typically appear years after the disease develops. 

According to the Alzheimer’s Association, some early dementia symptoms (contrasted with normal signs of aging) are: 

• Memory loss that disrupts daily life.  Forgetting recently learned information, important dates or events, asking the same questions over and over, and increasingly needing to rely on memory aids or family members for things you used to handle on your own. A typical age-related change in memory that isn’t necessarily cause for concern, would be occasionally forgetting names or appointments, but remembering them later.
• Challenges in planning or solving problems. Changes in your ability to develop and follow a plan or work with numbers. You may have trouble following a familiar recipe or keeping track of monthly bills. You may have trouble concentrating and take much longer to do things than before. On the other hand, it’s normal to make occasional errors when managing finances or household bills.
• Difficulty completing familiar tasks. You may have trouble driving to a familiar location, organizing a grocery list, or remembering the rules of a favorite game. It’s not particularly concerning if you occasionally need help using microwave settings or recording a TV show.
• Confusion with time or place. You lose track of dates, seasons and the passage of time. You may have trouble understanding something if it is not happening immediately. Sometimes you may forget where you are or how you got there. On the other hand, it’s not unusual if you get confused about the day of the week but figure it out later.
• Trouble understanding visual images and spatial relationships.  You could experience vision changes that may lead to difficulty with balance or trouble reading. You might have problems judging distance and determining color or contrast, causing issues with driving. This is different from vision changes related to cataracts.

Note: This item first appeared in Kiplinger’s Retirement Report, our popular monthly periodical that covers key concerns of affluent older Americans who are retired or preparing for retirement. Subscribe for retirement advice that’s right on the money.

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