En español | Dementia is one of the most dreaded conditions worldwide. Compounding that dread is our frankly awful success rate in treating deterioration of the brain. There is no cure, and no new drugs to treat symptoms of dementia have been approved for 15 years, as 99.6 percent of drug trials end in failure and well over 400 dead ends have cost billions of dollars.
That’s bad, but not as hopeless as it sounds. Researchers believe that we will not only see new treatments in the near future, but also that new diagnostic approaches can improve the effectiveness of the two main drugs we have.
Historically, new treatments for dementia have come at a glacial pace because the condition poses a series of high hurdles: Dementia is not fully understood; it has dozens of underlying causes; the brain is walled off by the blood-brain barrier, making targeted drug therapies a challenge; and, maybe most important, for many years doctors couldn’t even officially diagnose Alzheimer’s until the patient was dead and an autopsy performed.
“We couldn’t approve treatments if we didn’t even know what we were treating and couldn’t measure progress,” says Janet Woodcock, M.D., director of the Center for Drug Evaluation and Research (CDER) at the Food & Drug Administration.
Treatments to lessen symptoms
Currently there are two primary types of FDA-approved medications to lessen the symptoms of Alzheimer’s disease — the form of dementia most heavily targeted by pharmaceuticals. These two types are cholinesterase inhibitors and an NMDA receptor antagonist, according to Claudia Padilla, M.D., medical director for research at Cognitive and Behavioral Neurology Associates/Baylor AT&T Medical Center in Dallas.
Essentially both of these long-winded, science-y sounding drugs aim to serve one purpose: to keep your brain cells communicating with one another so your brain can function normally. That’s important because Alzheimer’s causes plaques to form between nerve cells, making it hard for them to send signals. These drugs try to keep open as many channels of communication as possible.
The first type, cholinesterase inhibitors (which you might know by their more common brand names Aricept, Exelon and Razadyne) are designed to maintain healthy levels of a chemical called acetylcholine. Acetylcholine is a neurotransmitter that helps send messages between nerve cells in the brain and plays a key role in memory. Acetylcholine breaks down naturally in everyone, but the process is much worse in people with Alzheimer’s, who have low levels of acetylcholine in their brain, Padilla says. By preventing acetylcholine from breaking down, this medication allows nerve cells to continue to communicate and that helps to stabilize some of the symptoms of dementia. Common side effects of cholinesterase inhibitors include loss of appetite, nausea, diarrhea, headache and lowered heart rate.
The second type of treatment is an NMDA receptor antagonist (which you might have heard about as memantine or Namenda) and it also works by keeping lines of communication open between brain cells. Only this time, these medications target a neurotransmitter called glutamate that also is involved with learning and memory. Glutamate is critical because when brain cells are damaged by Alzheimer’s disease, they pump out too much glutamate, which damages even more brain cells. “Memantine blocks the effects of excess glutamate,” Padilla says. Common side effects of memantine are dizziness and fatigue, she says.
The two drugs often are used together, especially in later stages of the disease. Namzaric, which was approved in 2014, combines both types of drugs in one medication for more convenient treatment.
For Lewy body dementia, often found in individuals with Parkinson's disease, which Robin Williams famously suffered from, doctors often will add medications like carbidopa-levodopa (Sinemet) to reduce tremors and other parkinsonian symptoms, says James Leverenz, M.D., director of Cleveland Clinic’s Lou Ruvo Center for Brain Health.
“We sometimes also prescribe drugs for hallucinations or mood [such as risperidone (Risperdal) and olanzapine (Zyprexa)], because they [patients] can be depressed frequently,” Leverenz says, noting that it’s best to work with someone who specializes in treating this form of dementia because some traditional antipsychotic drugs like haloperidol (Haldol) can aggravate the parkinsonian symptoms.
A SAGE treatment
Right now a third “treatment” is taking hold in the Alzheimer’s medical community: prompt diagnosis and subsequent treatment before symptoms even start.
Currently, experts estimate that only half of Americans with Alzheimer’s have been formally diagnosed, and the majority of cases are not diagnosed until six years after symptoms start. “That’s a serious problem,” says Jim Ray, head of research for the Neurodegeneration Consortium at MD Anderson Cancer Center. “We’ve been treating too late in the disease process for the drugs we have to work well.”
There’s an enormous push toward improved, early diagnosis, Ray says. Research settings are using new brain-scanning techniques such as tau PET imaging and developing biomarkers that will help doctors identify changes in the brain and confirm an Alzheimer’s disease diagnosis before symptoms even begin, which may be key for successful treatment with current and future medications.
But you don’t have to wait for those sophisticated screening techniques to reach mainstream medical facilities. You can start to work directly with your doctor right now using a recently developed tool called the Self-Administered Gerocognitive Examination or SAGE test, a simple pencil-and-paper test developed to show how well your brain is working, says Douglas Scharre, M.D., who helped develop the test and is the director of the Center for Cognitive and Memory Disorders at the Ohio State University Wexner Medical Center.
Your doctor can administer the SAGE exam as part of your regular annual check-up, or you can take it at home and set up an appointment to review the results with your doctor, Scharre says. (You can find it here.) It takes about 15 minutes and evaluates function in all areas of the brain and cognition, including language, memory and problem-solving.
Either way, your doctor will score the test and discuss the results with you. If you take it and have a low score, it’s like getting a high blood pressure reading or worrisome blood-work results, you and your doctor know to take further action, Scharre says. The test cannot diagnose Alzheimer’s or dementia (and certainly should not be used to self-diagnose); it gives your doctor a baseline of your (or a loved one’s) cognitive function so that it can be tracked over time and any changes noticed.
Research shows that the test correlates very well with medical cognitive testing and identifies 80 percent of people with mild cognitive issues; 95 percent of people with no cognition issues have normal scores. You can take it every year to catch minor changes that you could otherwise miss for years. It’s cheap and effective and allows doctors to start treatment and maybe prevent worsening cognition, says Scharre.
Clinical trials and FDA paving the way
“Now that we have better diagnostic tools and sensitive cognitive screening, like imaging and biomarkers, we can include trials for people in the earliest stages of the disease process who have no symptoms and we can measure even subtle changes in the progression of the disease, which maximizes our probability of finding better treatments,” says Woodcock.
What’s more, earlier this year, the FDA announced revised guidelines for neurological disorders that for the first time will green-light clinical drug trials for preclinical Alzheimer’s, the stage before dementia symptoms become apparent.
This represents a major policy shift that the administration hopes will lead to better treatment at the earliest stages of the disease, where medical intervention is most promising, and open the door to treatments that stop the disease process before it progresses.