Could we be on the cusp of catching Alzheimer’s before it starts?
The key to slowing cognitive decline is diagnosing the disease as early as possible. And that’s exactly what Johnson & Johnson scientists are relentlessly pursuing.
Anyone living with Alzheimer’s disease (AD)—or living with someone who has it—likely knows how profoundly frustrating, painful and heartbreaking the disease can be.
Alzheimer’s disease, which is the seventh leading cause of death globally and the most common cause of dementia, not only causes memory loss but also erodes a person’s ability to communicate and may also give rise to changes in personality and the loss of independence.
The risk of Alzheimer’s increases with age, most often affecting those who are 65 and over. And once adults start losing their brain function, it’s irreversible.
But growing research shows that if the disease is caught in its earliest stages, cognitive decline may be slowed, and there are more potential options for treatment.
“We want to diagnose people when they still have as much brain function as possible,” says Fiona Elwood, Ph.D., Neurodegeneration Disease Area Stronghold Leader, Neuroscience, the Janssen Pharmaceutical Companies of Johnson & Johnson. “Our goal is to extend and protect that period of life, so that people can stay connected with their loved ones and still look after themselves and be independent.”
It’s crucial work that Johnson & Johnson has been pursing for decades. For National Alzheimer’s Disease Awareness Month, here’s a look at what we now know about the disease, plus the latest examples of how the company has committed to developing tools and tests that may catch this fatal disease early on.
Changes in the brain happen earlier than you think.
The hallmarks of AD begin with changes in the brain. “There is an accumulation of plaque, known as amyloid, in the brain, as well as a buildup of a tangle of protein called tau,” says Simon Lovestone, Ph.D., Global Head of Discovery and Translational Research, Neuroscience, Janssen. Those tangles of tau fill up neurons—the cells in the brain that send and receive messages—preventing them from working and eventually killing them.
Twenty years ago, we were taught that Alzheimer’s can only be definitively diagnosed after the person has died, via an autopsy of the brain. That has all changed.
As these neurons become impaired, they can no longer send signals to each other, and symptoms of AD begin. While the exact timeline is unclear, research estimates that it might take between 10 to 20 years from when plaque accumulates in the brain to when people first start noticing symptoms.
Symptoms of Alzheimer’s disease go beyond memory loss.
One of the first AD symptoms to show up is memory loss, which can interfere with everyday life. People with the disease may start forgetting information that they’ve recently learned, or people’s names and important dates. They might also ask the same questions repeatedly. The ability to concentrate and to do things that used to be easy, like follow a recipe or remember the rules of a familiar game, also tend to worsen.
Confusion regarding time and place is another common symptom; a person with the disease may not remember the date or even what month it is; they may also become uncertain about how much time has passed. Some people may develop vision problems that impact their balance or their ability to read or judge distance (which can impair driving or lead to falls). Language issues may also develop, whether it’s struggling with words or calling something or someone by an incorrect name.
People with AD may lose things or put objects in odd places (like a shoe in the refrigerator), and their personal grooming may deteriorate. A particularly hard change for loved ones of people with AD: They may experience changes in their personality and their mood, becoming angry, scared, anxious or depressed.
Blood tests may hold promise for earlier diagnosis.
When you look at how AD has been diagnosed over the years, it’s striking how far things have come. “Twenty years ago we were taught that AD can only be definitively diagnosed after the person has died, via an autopsy of the brain,” says Elwood. That has all changed thanks to advances in brain scans and other tests that can show the accumulation of amyloid and tau, plus other biomarkers.
PET imaging scans, for example, can now measure the amount of amyloid and tau accumulation in the brain. But, explains Elwood, one drawback is that it’s a complicated test that involves injecting a radio-labeled tracer into the patient to scan their brain and can only be administered in certain healthcare settings.
Lumbar punctures are other tests that can measure changes in proteins in the cerebrospinal fluid that originated in the brain, though these tests may be difficult for some patients to undergo.
We want people to be able to get the test during their physical, so that the doctor can tell them: ‘You have a risk for heart disease and a risk for Alzheimer’s disease.’
Around three years ago scientists, including those at Johnson & Johnson, started researching a less invasive way to look for changes in the brain via a blood test. “We’ve developed an investigational sensitive blood test that measures one of the earliest biomarkers that change in people with AD,” says Elwood. The goal of this blood test is to identify the disease in patients at a much earlier stage, and researchers hope to start clinical trials soon.
Eventually, if approved, the hope is that this test will be administered by a primary care doctor rather than a specialist. “If you’re trying to treat patients early, who do they go to? They go to their primary care doctor,” Elwood says. “We want people to be able to get this test during their physical so that the doctor can tell them, for example: ‘You have a risk for heart disease and a risk for Alzheimer’s disease.’ Then people at risk can be guided toward preventive care, such as regular physical and social activity and a heart-healthy diet—and we hope, in the future, they’ll also be guided toward preventive therapies.”
Advanced technology is also being utilized to measure cognition.
Data scientists and digital health experts at Johnson & Johnson are also developing ways to use advanced technology—specifically artificial intelligence (AI) and augmented reality (AR)—to identify people who are at the very earliest stages of cognitive decline. This test could eventually be used for diagnosing AD, says Elwood, or to track more precisely how the disease progresses.
“Struggling with language is an early sign of the disease, so our goal was to find a way to detect subtle differences in how someone communicates over time,” says Gayle Wittenberg, Vice President, Neuroscience, R&D Data Science & Digital Health, Janssen. “The tool we’re leveraging uses a machine learning algorithm to measure changes in speech patterns as well as voice, pitch and tone, which can then be analyzed to help identify any speech patterns that could be possible predictors of early AD.”
Right now, the gold standard for assessing cognition requires a patient to travel once every six months and be tested for three hours with different paper and pencil tests. With an at-home system, people could test themselves more frequently and immediately flag any changes and patterns in cognitive function.
Also in development: an AR system that patients can use at home via an app that helps assess cognitive ability. “Essentially, the app superimposes a game on top of your environment,” says Wittenberg. “For example, via the app you’d be looking around your room, and the game would ‘hide’ an object somewhere, and you have to walk around and find it. This tests spatial reference, and the system can be developed to test different types of cognitive ability and function.”
Since the patient will be able to access this AR app at home, they can use it repeatedly, which is important for monitoring any cognitive changes, adds Elwood. “Right now, the gold standard for assessing cognition requires a patient to travel once every six months and be tested for three hours with different paper and pencil tests.” With an at-home system, she adds, people could test themselves more frequently and immediately flag any changes and patterns in cognitive function.
Elwood points out another advantage: “There can be variability in test results depending on circumstance, such as having a bad night’s sleep or a difficult day with your kids.” Those external factors affect the test results. Therefore, more frequent testing could help establish a more accurate baseline.
Treatment options to slow down disease progression are in the works.
Beyond diagnostic advances, there is also hope on the horizon for new treatment options.
Lovestone, who has been studying the role of tau in AD for his entire professional career, sees great potential in the future of AD treatment—particularly in the area of tau.
“Most people in the field think that it’s this process of tau pathology—that is, spreading from neuron to neuron—that may cause symptoms that patients suffer from,” rather than the amyloid plaques, he says. “At Johnson & Johnson, we have a program of investigational antibody-based therapeutics that are designed to prevent the spread of tau pathology when it is in the space between neurons.”
Right now, the therapeutics are being evaluated in late-stage clinical trials to see if they might prevent AD from spreading.
“I’ve always thought that a therapeutic against tau could be perhaps more effective than other therapeutic approaches,” Lovestone says. “And as we get closer to the answer to that question, I’m becoming ever more optimistic and excited.”