“So many building blocks to disease-modifying treatments are coming together,” says Cleveland Clinic’s JamesLeverenz, a neurologist who directs the Cleveland Lou Ruvo Center for Brain Health. “And we’re better understanding why the disease varies from person to person.” Leverenz, who also leads the Cleveland Alzheimer’s Disease Research Center (one of 31 NIH-funded Alzheimer’s disease research centers), points to game-changing advances like these.
New blood tests tell who’s at risk
Not so long ago, brain scans and lumbar punctures to collect spinal fluid were the only ways doctors could see early brain changes associated with Alzheimer’s. Now blood tests offer a less invasive, more affordable and (soon) more widely available option. The first, PrecivityAD, helps determine the presence of amyloid plaques in the brain, a disease hallmark.
Earlier interventions
Biomarkers like amyloid are improving how researchers screen study subjects and flag patients for early treatment. For example, scientists are combining other new blood tests, such as one for another protein called tau, with genetic and cognitive testing to predict who’s at high risk. “We’re identifying people with disease at its earliest stages, even years before they have symptoms,” Leverenz says. The goal: finding interventions that prevent or delay any impact on daily life.
Highly personalized treatments
Already, many different types of dementia have been identified (like frontotemporal, vascular and Alzheimer’s); now researchers are focusing on atypical Alzheimer’s forms. These mystifying disorders have biomarkers that suggest Alzheimer’s but cause symptoms like those seen in other forms of dementia. “Just like cancer isn’t just one thing called ‘cancer,’ dementia isn’t just one thing either. There are many subtypes, and each reacts to therapeutics differently,” Leverenz says. Treatments will become increasingly individualized, he says.
Big data speeds research progress
Researchers can now analyze tens of thousands of de-identified (anonymous) medical records to find patterns associated with dementia. For example, Cleveland Clinic’s FeixiongCheng found a statistical link between taking sildenafil (Viagra) and reduced risk for Alzheimer’s. These artificial-intelligence-harvested clues don’t prove associations but provide shortcuts to ideas to test.
The first drug to slow disease
The first disease-slowing AD treatment, aducanumab (Aduhelm), was approved by the FDA in 2021. Controversial due to its high costs, dangerous side-effect risks and limited effectiveness, it’s considered a breakthrough because the five other Alzheimer’s drugs only ease symptoms. Dozens of disease-modification clinical trials, along with an Alzheimer’s vaccine, are in the pipeline. Amazingly, 99 percent of AD drugs tested have failed. Researchers now think they either were intervening too late (after brain damage had occurred) or studied the wrong subjects (people who were misidentified as having AD because of poorer screening tests).
Pinpointing pathways to prevention
Exercise, sleep and, increasingly, having strong social ties are now seen as ways people can protect brain health. Exciting new research is looking at how the immune system and inflammation influence Alzheimer’s, Leverenz adds. “We’re so much further along than we’ve ever been,” he says.
Maria Shriver: Good news for women
Two-thirds of those with Alzheimer’s are women. So are two-thirds of caregivers. One in two women will be diagnosed with a neurological disorder in her lifetime (including Alzheimer’s, Parkinson’s disease and stroke). “Women’s health trajectories are different from men’s. We’re intent on figuring out why,” says Maria Shriver, founder of the Women’s Alzheimer’s Movement (WAM), a nonprofit blending education, fundraising, and advocacy. Pressing the fast-forward button on those efforts: In early 2022, the WAM became part of Cleveland Clinic’s pioneering research and treatment health system. The partners had created the first Alzheimer’s disease prevention center for women, the WAM Prevention Center at Cleveland Clinic, in Las Vegas in 2020. “When I first got involved [with Alzheimer’s] more than 20 years ago, there was nothing about lifestyle or prevention. Now some researchers say that 50 to 60 percent of cases could be prevented or delayed,” Shriver says. She’s especially excited about research into the role of hormones—should women take them, when, for how long. “The brain does change around menopause, I’ve always had a hunch, and WAM is [investigating] that,” she says. “Women are coming to the clinic saying, ‘I don’t want to just help me, I want to help the women who come behind me.’”
Sources
PrecivityAD: “Major Research Findings Highlight Effectiveness of PrecivityAD Blodd Test That Clinicians Use to Aid in Alzheimer’s Disease Diagnosis” Nature Medicine: “Prediction of Future Alzheimer’s Disease Dementia Using Plasma Phospho-Tau Combined With Other Accessible Measures” National Institutes of Health: “Viagra Associated With Reduced Risk of Alzheimer’s Disease” Alzheimer’s Association: “Alzheimer’s Disease Drug Development Pipeline: 2020” Drug Discovery and Development: “99% of Alzheimer’s Drug Trials Fail, Study Says”
