New Treatments for Alzheimer's Disease

Elaine K. Howley

For anyone who has or knows someone who has Alzheimer's disease -- a progressive and irreversible form of dementia that's ultimately deadly -- it can sometimes be difficult to find hope. But in mid-November a new drug to treat the disease began garnering a lot of attention.

Called aducanumab, the drug is made by pharmaceutical company Biogen and is currently under review by the U.S. Food and Drug Administration. Their decision about its future is expected by March 2021. If it's approved, it'll be the first drug in 17 years to be approved by the FDA for the treatment of Alzheimer's disease.

[READ: Questions to Ask When a Loved One Is Diagnosed with Alzheimer's or Dementia]

Current Treatments for Alzheimer's

The prospect of a potential new drug to treat Alzheimer's offers families dealing with the effects of the disease good reason to look forward.

"Alzheimer's disease is the most common cause of dementia," says Dr. Rawan Tarawneh, assistant professor of neurology at the Ohio State University Wexner Medical Center in Columbus. A progressive, neurodegenerative brain disease, Alzheimer's "affects memory and cognitive functions including problem-solving, orientation, language and visual spatial skills," which eventually lead to functional problems that interfere with the person's ability to perform daily activities such as driving and managing finances, she explains.

In severe cases, "basic activities such as dressing, walking and eating also become difficult."

In addition to cognitive problems, Alzheimer's disease can also bring on a range of behavioral and emotional changes, including:

-- Depression.

-- Anxiety.

-- Irritability.

-- Hallucinations.

-- Delusions.

-- Changes in sleep or appetite patterns.

"AD is the sixth leading cause of death among U.S. elderly, accounting for more deaths than breast and prostate cancer combined," says Tarawneh. Here in the U.S., a new AD diagnosis is made every 65 seconds.

The problem is only growing, she adds. "The number of affected individuals is expected to triple in the next 30 years. It's estimated that by 2050 there will be over 30 million people in the U.S. and over 100 million people in the world with AD," making Alzheimer's a "global epidemic."

This coming surge of cases is especially concerning because there's currently no cure for Alzheimer's, "and we have not been able to identify methods or treatments that can effectively prevent, slow down or reverse" the changes that occur in the brain that cause the symptoms of AD, Tarawneh says.

Currently, the treatments that are available focus on addressing symptoms. These medications fall into two major categories, Tarawneh explains:

-- Cholinesterase inhibitors, which are used in all stages of AD. These include Aricept (donepezil), Exelon (rivastigmine) and Razadyne (galantamine). These medications are prescribed to treat symptoms related to memory, thinking, language, judgement and other cognitive processes, the Alzheimer's Association reports.

-- Memantine, which is used in moderate to severe stages of AD. Namenda is the brand name for this type of medication, which is used to improve memory, attention, reason, language and the ability to perform simple tasks, the Alzheimer's Association reports. It can be used alone or with other treatments.

These treatments can "help stabilize the clinical symptoms by slowing down the clinical progression and allowing individuals to maintain their current level of functioning for several years," Tarawneh says. This is great, but the problem is, even with that slowing of the progression, the disease will continue to get worse and patients will decline.

In addition to those treatments, many people with AD may also be prescribed other medications that "target behavioral and psychiatric symptoms" that are common in various types of dementia. These medications may include:

-- Antipsychotics.

-- Antidepressants.

-- Anxiolytics, also known as antianxiety medications.

-- Mood stabilizers.

-- Sleep aids.

-- Appetite stimulants.

[READ: Homecare for a Loved One With Alzheimer's or Dementia.]

More on Aducanumab

The investigational treatment aducanumab is a monoclonal antibody that targets aggregated amyloid protein -- clumps of proteins in the brain that are a hallmark of Alzheimer's disease.

Tarawneh explains that there have been "two large Phase 3 studies involving 3,285 patients at 348 sites in 20 countries" looking at the efficacy of the medication. Study participants were followed closely for 18 months.

"In both studies, the drug was effective in removing amyloid aggregates from the brain," as measured with imaging equipment. However, only one study showed that the drug "was effective in reducing cognitive decline." The other study "did not show any clinical benefits. In other words, even though amyloid seemed to be effectively reduced, this only translated into clinical benefit in one study but not the other," she explains.

This poses a challenge for the FDA as it assesses whether to approve the drug. Biogen notes that some patients with more rapidly progressing disease were included in the study, and that may have made the drug appear less effective. Biogen also argues "that the negative results of one study does not 'detract from the persuasiveness' of the positive study," Tarawneh says.

But the FDA Peripheral and Central Nervous System Drugs Advisory Committee was not convinced that the overall data presented was strong enough to support FDA approval of the medication. Their overall vote was negative. It's now up to the broader FDA to review the data and the committee's input to make its own assessment and issue a verdict next spring.

[SEE: Normal Brain vs. Brain With Dementia.]

The Future of Alzheimer's Treatment

Aducanumab has nabbed lots of headlines lately as the FDA reviews the clinical trial data, but it's not the only drug that could change the treatment of AD in the future. In addition to symptom-modifying drugs that slow the progression of the disease, several companies are also working hard to create even better treatments that go to the root of the problem and reverse the disease process itself.

These disease-modifying medications "target disease pathology," Tarawneh says, and are an exciting frontier in treatment of Alzheimer's. "As of early 2020, there were over 120 investigational AD treatments in different stages of clinical trials," she notes.

In the past, many of the disease-modifying medications targeted amyloid proteins that accumulate in the brain and cause a disruption of cognitive function and death of brain cells. This type of medication has been somewhat disappointing, though, so some researchers have turned their attention to targeting another protein involved in the development of Alzheimer's. This protein is called tau.

Tau appears to be "more closely related to cognitive function and brain atrophy," Tarawneh says, so offers a potentially very promising alternative to amyloid-targeting treatments.

In addition to targeting tau, researchers are looking to medications that address other changes that occur in the Alzheimer's brain in an attempt to alter the course of the disease. Treatments that slow or reverse inflammation, immune dysfunction and damage to the blood vessels in the brain are also being investigated. These have all been implicated in some way in the inexorable advance of Alzheimer's disease.

Tarawneh notes that in trying to find the answer to what will work best, there's been an effort to get patients enrolled in clinical trials before they start showing symptoms of AD "to increase the chances of success in improving clinical outcomes. This is because by the time patients with AD have even mild memory loss, they have already sustained significant neuronal loss, and it may already be too late to intervene, as these changes are irreversible once they happen."

The idea is to get a head start on the disease before patients become symptomatic.

As science continues to unravel the mysteries of how AD develops and progresses, we develop better treatments for it, Tarawneh says. She believes "the future of AD therapeutics lies in personalized medicine approaches, in which the choice of drugs to use will be individualized based on biomarker and imaging data, disease stage and other individual factors."

In other words, at some point in the future, a blood test or another kind of biological analysis may reveal specific details about an individual's disease pattern which could allow doctors to prescribe super targeted treatment that looks different for that person than for someone else with Alzheimer's.

Much like how cancer treatment is becoming increasingly personalized and tailored to the biology of the individual's specific tumor, so too will AD treatment become highly specific to each individual patient.

While there's reason to hope, there's a lot more work to be done before Alzheimer's disease can be cured. The Alzheimer's Association notes that "ultimately, the path to effective therapies is through clinical studies." You can access information about current trials and enroll yourself or a loved one via their TrialMatch site.