Most people are now aware of at least some of the more daunting facts about Alzheimer’s disease:

• An estimated 6.9 million Americans have the disease — a tally estimated to double by the year 2050.
• Nearly one of five Medicare dollars is spent on people with dementia; that amount is expected to rise to one in every three dollars by 2050.
• While the disease progresses differently in different people, a person with Alzheimer’s lives for an average of four to eight years after diagnosis, but can live as long as 20 years.
• Given the current state of available treatments, it’s estimated that one in three seniors will die from Alzheimer’s or some other dementia.

Another hard truth is there are currently no medications that can cure Alzheimer’s — or even stop it from progressing. At the recent “Aging in America” conference sponsored by the American Society on Aging, a panel of neuroscientists, medical researchers, and healthcare advocates sat down to explain to a capacity crowd why that is true.

What’s Available Now

There are currently 127 pharmaceutical treatments for Alzheimer’s in clinical trials, but only a handful have been approved by the U.S. Food and Drug Administration (FDA), and each of them have limitations and recommended applications.

Drug regimes currently used to treat Alzheimer’s take two approaches, sometimes in combination with each other. The first approach is intended to slow the progress of the disease. The second treats symptoms associated with dementia.

Anti-amyloid treatments are designed to remove a protein (beta-amyloid) that accumulates in the brain, causing the formation of plaques. The drugs slow the progression of dementia in some patients. They are most effective when administered in the early stages of disease development.

Cholinesterase inhibitors and glutamate regulators target the chemical messengers in the brain. They are prescribed to treat symptoms related to memory, thinking, language, judgment, and other thought processes.

Other drugs that may be prescribed to treat symptoms include receptor antagonists (typically used in the treatment of insomnia in patients with dementia) and atypical antipsychotic medications (typically prescribed to treat agitation). The use of antipsychotics to control behavior, however, has sparked concerns about overmedication  in some settings.

Nine drugs, each aimed to work in a distinct way at various stages of the disease, are currently FDA-approved for the treatment of dementia or its symptoms.

Common side effects associated with these drugs include nausea, vomiting, constipation or increased frequency of bowel movements, headache, and dizziness.

A drug once thought to be a blockbuster advance in Alzheimer’s treatment was withdrawn in 2024 despite winning fast-track FDA approval. The drug aducanumab (brand name Aduhelm) was so expensive that Medicare premiums were raised to pay for it. Yet the clinical data upon which the drug was based was so shaky that several members of the FDA advisory panel resigned to protest the agency’s decision to approve it without requiring more substantial proof of its efficacy.

Some of the current medications are controversial. While Lecanemab is advertised as achieving a statistically significant reduction in the rate at which Alzheimer’s patients decline, some scientists argue that the improvement in clinical scores is so small that it would be “imperceptible in real life.” One study found that memantine might have a small clinical benefit for patients with moderate-to-severe Alzheimer’s Disease, but no benefit for patients with a mild impairment.

Once the disease has damaged the brain, the damage is probably irreparable. According to Phyllis Ferrell, a former executive for Eli Lilly who is a vocal advocate for dementia research, the challenge is to stop the disease from progressing before it causes substantial damage. The failures of drug trials are disappointing, but each one brings science closer to a full understanding of the disease and to new treatments.

Hurdles to Overcome

A number of factors have increased the challenge of securing a pharmaceutical treatment or cure for Alzheimer’s disease.

Symptoms are usually slow to show. Proteins in the brain begin to clump and nerve cells begin to show damage up to 30 years before a person will exhibit any outward symptoms of Alzheimer’s. By the time many people are actually diagnosed, it is too late for many of them to benefit from drugs aimed to treat symptoms in the early to moderate stages of the disease. And starting treatment too early risks longterm exposure to medications that may have strong side effects.

Drug testing is expensive and time-consuming. According to a 2021 NIH report, the total cost of developing an AD drug is  $5.7 billion per drug. The Journal of the Alzheimer’s Association  wrote that AD is one of the most difficult therapeutic areas for drug development, with a failure rate of nearly  a 100%.

Kenneth L. Davis, a medical researcher who developed the Alzheimer’s Disease Assessment Scale, used to test drugs’ efficacy, is also frustrated by the necessarily lengthy research process. In a thesis titled “How to Accelerate the Search for Alzheimer’s Drugs,” he notes that the rigorous review currently required by the Food and Drug Administration (FDA) from preclinical and animal toxicology through the various phases and analyses of trials can consume up to 24 years — and that’s before a drug is submitted to the FDA for final review and approval.

And Eli Lilly’s Ferrell also points out that it took her company 17 months to get the required 1,000 participants for a particular clinical trial. She says only 50% of those with Alzheimer’s actually get diagnosed; and by then, it is too late for them to qualify for the trials requiring lengthy monitoring.

Little incentive for drug companies. Biomarkers — a smashup of “biological markers” — are the indications of a disease that can be objectively measured and reproduced. Davis laments that Alzheimer’s trials must rely on biomarker indications of the disease rather than an analysis of clinical symptoms, yet the FDA has never approved a medicine solely on biomarker evidence. He says it’s the reason many pharmaceutical companies concentrate instead on “less challenging” diseases: “High-risk, long, costly trials of experimental drugs that leave little patient life once approved hardly make for a compelling business model,” Davis notes. “There is little assurance of the ability to recoup investments, no less earn a profit, even if a company succeeds in the arduous effort of creating, testing, and winning approval of an Alzheimer’s medicine.”

(This article has been updated November 2024 since it originally published April 2018.)