By Matt Schur from the AMT Pulse.
Alzheimer’s begins slowly—a once-known word slips away, a missed appointment, a repeated story. Time is greedy, taking more and more. The faces of friends and family become unrecognizable. Everyday objects, a mystery.
“You can see it in the way people get lost, lose abstraction or lose insight,” says Amy Arnsten, PhD, the Albert E. Kent Professor of Neuroscience at Yale School of Medicine and Professor of Psychology in Yale’s Faculty of Arts and Sciences. “Slowly, the person starts disappearing.”
Often referred to as the long goodbye, Alzheimer’s steals away from not just the individual, but from the people closest to them. This toll—on the person, on loved ones—makes it one of the most challenging diseases, says Jason Karlawish, MD, Professor and Co-director of the Penn Memory Center at the University of Pennsylvania. The difficulty isn’t relegated to these cumulative emotional effects; the nature of the disease has stumped the medical community for years, too. “It’s quite challenging to measure the brain,” Karlawish says. “It’s not an easy organ to measure, like the heart or the lungs. And a careful diagnostic work-up requires input from the very person who’s having cognitive problems, and those problems can frustrate their ability to explain what’s wrong.”
For much of the 20th century, the only method to confirm if someone even had Alzheimer’s disease was a posthumous autopsy. “Fifty years ago, all we had were silver stains and neuropathology,” rnsten says. “We could see what was going wrong but not understand it.”
A new era has emerged. With the approval of lecanemab, 2023 marked the first year a therapy existed to treat the underlying cause of Alzheimer’s. This year, the U.S. Food and Drug Administration (FDA) approved the first blood test to diagnose Alzheimer’s. Together, they spell the start of a promising future to reckon with one of the most prolific, devastating diseases.
As the number of people with Alzheimer’s is expected to nearly double by 2050, the timing couldn’t be better. Or, so it seemed. Just as research reaches new heights, progress could unravel as widespread funding constraints—including cuts to programs and universities across the country—shrink, pause or outright cancel Alzheimer’s work.
Diagnostic Improvement
Alzheimer’s is the most common cause of dementia, which is a broader term to describe issues with memory, thinking skills and the inability to carry out everyday activities. Most Alzheimer’s patients first experience issues in their 60s, but the pathology can develop 20 years before symptoms appear, making early diagnosis both difficult and critical.
Diagnostic capabilities lagged for years until the late 1980s and 1990s, with the advent of positron emission tomography (PET) scans and cerebrospinal fluid tests. Even still, diagnosis continued to rely on a combination of memory tests, imaging and observation.
That could be changing with the new FDA-approved blood test, which correctly identified that patients with memory problems had Alzheimer’s 90% of the time, according to research published in JAMA. Dementia specialists using standard methods—not including PET scans or spinal taps—accurate 73% of the time; primary care physicians were accurate 61% of the time.
Earlier detection allows for earlier treatment, which is when therapies are most effective. Greater diagnostics also allow for better representation in clinical trials, with improved abilities to see if treatments are effective. These tests could also break down socioeconomic barriers, especially helpful in areas where it was previously difficult to get such a diagnosis, whether from patient financial constraints or from a lack of access to specialists or equipment.
“The hope is that if we give treatments earlier, we will be able to really stave off the disease, not just slow it. The rationale is that the earlier you get treatment, the more effective it can be, because then you have a dead neuron, you can’t replace it. So if you’re already at a point where you’ve got major symptoms, it’s too late to stave off disease,” Arnsten says.
For now, researchers say the tests should be part of a larger screening process and only used for people with memory problems or cognitive decline. Researchers also note that PET scans or spinal taps remain the best option to most accurately determine if people have Alzheimer’s.
New knowledge brings new challenges, too. Karlawish says that identifying the disease too early may open the door to discrimination. “We’re going to face a future where the Alzheimer’s label is applied to people who seem cognitively normal,” he says. “That label is emotionally charged, stigmatizing. We have to think carefully about how society will handle that.”
Slowing the Disease
Until recently, researchers only had the ability to treat symptoms of Alzheimer’s but never the underlying cause. Lecanemab’s 2023 approval is “unprecedented and really quite exciting,” Karlawish says. “Unlike other drugs, lecanemab targets one of the causes that make brain cells dysfunctional and die.”
The drug targets amyloid beta, a protein that accumulates in the brain and disrupts communication between neurons. By clearing these plaques, lecanemab appears to delay cognitive decline—roughly by 27% in clinical trials. A modest gain, but in the face of no prior treatment, it’s a major step forward.
The drug is not without complications. It’s expensive and requires biweekly infusions and regular MRI scans to track complications. Patients have experienced brain swelling and bleeding from it. And, in the original study, four of the more than 1,600 patients died, potentially because of the drug. As Arnsten highlights, though, these complications can be associated with people who have Alzheimer’s anyway and that Alzheimer’s comes with its own serious complications.
Patients have to meet strict requirements to get the drug, with one estimate saying that fewer than 20% of patients met the criteria for treatment. Research teams are now trying to reduce these barriers. “Innovations in drug delivery, efficacy and safety promise an era of more convenient and effective treatments for patients and families,” Karlawish says. “We’re seeing new versions of drugs under study that promise lower risks and easier delivery.”
Research teams are also exploring a range of other approaches, everything from vaccines and gene therapies to lifestyle changes. Harvard researchers, for instance, found that lithium deficiency is one of the earliest contributing factors in developing Alzheimer’s, raising the prospect that increasing lithium intake early on can potentially prevent Alzheimer’s.
Arnsten’s part of a multidisciplinary research team focused on inflammation and the role it plays in neuronal death. “We’re trying to find strategies that would protect your brain as it ages,” she says. “Something you could start taking at 40 or 50—with no side effects.” Arnsten’s multidisciplinary team is exploring if they can reduce inflammation in the brain or target the pathways that cause it to build up, reducing the pathology. “There are multiple factors that increase the risk of getting Alzheimer’s, and many of these factors increase inflammation. Emotional stress and physiological stress at the molecular level causes toxic levels of calcium in cells, which ultimately drives Alzheimer’s pathology. So we’re trying to find strategies to restore and regulate calcium to keep it from reaching those toxic levels, or keep it from activating the culprits that then drive the pathology.”
Funding the Future
Much of the work in helping and assisting people with Alzheimer’s falls on family members, typically women. Overall, more than 11 million Americans provide unpaid care for someone with dementia, totaling more than 18.4 billion hours of care in 2023, according to the Centers for Disease Control and Prevention. The Alzheimer’s Association estimates that unpaid care for people with dementia is worth more than $340 billion annually.
“We’re overlooking the vast community of caregivers,” Karlawish says. “Their needs are our patients’ needs. When a granddaughter steps out of the workforce to care for her grandmother, she’s losing income, education and opportunity. That loss will never be recovered. We have failed to engage in a productive conversation about what we need to do to create a system that will allow caregivers to work.”
As the country’s elderly population grows, the pressure on this unseen system will balloon, putting additional strains on Medicaid and Medicare, which currently help cover costs. To make up this gap, Karlawish says there should be subsidies for caregivers, similar to what parents get with child tax credits.
Pressure on caregivers is one major funding concern. The other is what’s happening with research institutions. “We’re in an era of utter uncertainty,” Arnsten says. Arnsten’s lab has been working on inflammation research for more than 20 years. What worries her most going forward is funding availability in the wake of President Donald Trump’s administration’s cuts to healthcare, including changes to the National Institutes of Health (NIH), which have drastically reduced funding opportunities. Arnsten’s project has diminished because of federal spending cuts, she says.
“My understanding is that less than 5% of projects get funded now, and there are also cuts to universities, which will end up hurting us,” Arnsten says. “These treatments that we’re hoping will work are not being funded now. Many things that are just coming to fruition will be lost, so we may never know if they would have helped people.”
These cuts have disrupted the U.S.’ world-leading scientific infrastructure, Karlawish says. “I think that all Americans recognize that Alzheimer’s and other diseases that cause dementia are a fundamental threat to our liberty,” he says. “And I think all Americans are united in tackling the problem, but we’re not united around how best to do it.”