Will we ever find a cure for dementia?

Christopher H. van Dyck, M.D., professor of psychiatry, neurology and neuroscience and director of the Alzheimer’s Disease Research Unit at the Yale School of Medicine, points to two other

amyloid-clearing therapies that are far along in the clinical trial process — BAN2401 (from companies Biogen and Eisai) and gantenerumab (from Roche). If aducanumab doesn’t clear FDA review,

“you’d bet on one of these” becoming the first available treatment for Alzheimer’s disease, he says. Timing is one thing that sets the more successful and the promising anti-amyloid

therapies apart from their failed predecessors. Until recently, every trial that aimed to stop or slow the progression of dementia failed. “And it failed because we were giving these drugs

to people who have symptoms” of the disease, explains Michael Rafii, M.D., an associate professor of clinical neurology at the Keck School of Medicine of the University of Southern

California, and medical director of the Alzheimer’s Therapeutic Research Institute. FACTS AND FIGURES Alzheimer’s disease is the most common cause of dementia. Other common causes include

vascular dementia, Lewy body dementia, and neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. * 50 MILLION: Number of people worldwide with dementia. * 5.8

MILLION: Americans age 65 and older living with Alzheimer’s disease; almost two-thirds of them are women. * 14 MILLION: Number of Americans projected to have Alzheimer’s disease by 2050. *

$305 BILLION: Cost in U.S. of Alzheimer’s and other dementias in 2020. * $1.1 TRILLION: Without a treatment, projected cost in U.S. in 2050.  _Source: Alzheimer’s Association_ And giving

drugs to people who are symptomatic “is just too late,” he says. Somebody who has dementia already has widespread damage to the brain. “And unfortunately, when there’s any damage to the

brain, it’s permanent. You can’t go back. So early treatment is the key,” he adds. To Rafii’s point, trials targeting people in the earlier stages of their disease have seen success. One new

trial is even testing to see whether removing amyloid in people who have no Alzheimer’s symptoms will provide a preventative benefit. “So that’s a very exciting study,” Rafii adds.

Targeting the tau tangles is another big area of focus in the field. Unlike amyloid plaques, which can be present in the brains of people who are asymptomatic, tau tangles are more closely

correlated with clinical symptoms of the disease. Plus, their presence is seen in a number of neurodegenerative disorders, not just Alzheimer’s. “If we are able to find a therapeutic that is

helpful for really staving off the changes that occur with tau, we may actually be able to find therapeutics that are beneficial to multiple dementias,” the Alzheimer’s Association’s

Edelmayer says. 'CURE' COULD TAKE MANY FORMS As varied as the research pipeline is, most experts agree on one thing: When it comes to finding a way to stop, slow or prevent

dementia, it won’t boil down to one drug treatment or even one drug target. Rather, it will be a combination approach, perhaps involving drugs that clear the amyloid plaques, knock out the

tau tangles, target problem proteins and improve the synaptic health of the nerve cells in the brain. Patients may also receive nonpharmacological prescriptions from their doctors. Some of

the most recent research has shown that cardiovascular health and cerebral vascular health play a critical role in overall brain health throughout one’s lifetime. Exercise, diet and sleep

have all been shown to reduce risk of cognitive decline in adults. What’s more, a landmark study in 2018 showed that intensive blood pressure control significantly lowered the chances that

participants developed mild cognitive impairment. The mishmash of therapies likely won’t cure dementia, but as Rafii explains, “we have very few cures in medicine.” He and others in the

field, including the DDF’s Grant, are optimistic, however, that the ongoing advancements will lead to treatments that can delay the disease and improve the lives of millions. “What I’m

seeing is great progress in the building blocks, the foundation of new future therapeutic approaches,” Grant says.