Not Quite There: Updates Regarding Available Alzheimer’s Treatments

You may remember that the FDA has now approved 2 different medications to help slow down the progression of Alzheimer’s in patients who are in the early stages of the disease. Those are Leqembi and Kisunla. While neither can cure or reverse Alzheimer’s dementia, and they both come with potentially concerning (but uncommon) side effects of brain swelling or brain bleeds, they are nonetheless currently being taken by tens of thousands of patients worldwide with the hope that the medications can buy them some additional time to be active and with their families. Both of these medications target the beta-amyloid proteins that form plaques in the brains of people with Alzheimer’s. 

However, a new and somewhat controversial review of these medications is bringing into question the whole premise behind these drugs and whether they are of any value to the patients currently using them. Published in the Cochrane Database of Systematic Reviews, this research is part of an effort to provide gold-standard, independent reviews of health care research. For this particular review, expert scientists analyzed data from 17 previous clinical trials, involving over 20,000 participants, and included data from both medications that failed to come to market, along with the 2 current drugs available to patients in the early stages of Alzheimer’s. While researchers theorized that drugs designed to eliminate beta-amyloid proteins might slow down or even prevent Alzheimer’s disease, the Cochrane Review found no clinically meaningful beneficial effect for these medications and, in fact, suggested that Alzheimer’s researchers explore other directions in their research to combat Alzheimer’s. 

Many critics of this new Cochrane review question the research methodology of including failed medication as part of the review, along with the 2 medications that are currently in clinical use. And debate simmers about whether or not statistically significant results in a clinical trial are the same as meaningful and appreciable benefits to patients currently taking one of the FDA-approved drugs. The two approved anti-amyloid drugs only modestly slow down the disease progression in some patients, and no doubt do not fulfill the need, on their own, for effective treatments for Alzheimer’s. Yet, in some clinical settings, there is satisfaction in what these drugs are achieving. As one expert from Mass General made clear, “I wouldn’t accept the premise that anti-amyloid therapy has no clinical viability. At Mass General Brigham, one of the largest treatment programs in the world, we are seeing that these therapies can be delivered safely and can meaningfully slow progression for many patients with early-stage Alzheimer’s disease.“ Despite the debate in the scientific community about the efficacy of these 2 approved anti-amyloid medications and their value to patients and families, no one disputes that research needs to go well beyond this anti-amyloid approach to find additional and perhaps more effective treatments for persons with Alzheimer’s. For more about this controversial new study, click here.

Several new approaches to Alzheimer’s treatments are already under investigation. For example, researchers are targeting the Tau tangles in the brains of Alzheimer’s patients and are also considering the role that chronic inflammation plays in facilitating the rise of Alzheimer’s. Other avenues of research include an examination of the role of the central nervous system, rather than the brain, in causing Alzheimer’s. A recent research study cited the early symptoms of balance disruption and walking difficulty as indicators that Alzheimer’s may be detected early on in the nervous system of patients, which would suggest approaching treatments outside of the brain may be valuable. Another area of research beyond the anti-amyloid approach has to do with the connection between exercise and Alzheimer’s. In a recent study published in Cell, researchers focused on the leaky blood-brain barrier that often afflicts older adults, and whether exercise can produce a specific protein to help support and repair that barrier so that inflammation cannot leak into the brain and heighten the risk for dementia. The theory was demonstrated in mouse experiments and will next be studied in humans, though the results may not be known for many years.

Finally, researchers are also now beginning to tease out differences in the way Alzheimer’s is detected and manifests in women versus men, which may lead to further alternative approaches to treating Alzheimer’s. We know that ⅔ of Alzheimer’s patients are women. That may be because women live longer and most cases of Alzheimer’s are diagnosed in people in their 70s and 80s (and for people in their 90s, up to 50% will have some dementia). We also know that some of the standard cognitive tests for Alzheimer’s may not pick up cases in women the way they pick up cases in men. Apparently, a new study has shown that the Alzheimer’s timeline is different in men and women: Men tend to have more brain shrinkage early on and then stabilize, while women tend to be stable early in the disease process and then experience a subsequent steep decline. This perhaps means that not only research on effective treatments but even diagnostic testing may need to be more sex-specific going forward.

The one incontrovertible thing is this: While we have more understanding of Alzheimer’s than we previously had, and some therapies that can produce modest benefits for some patients, we are a long way from helping the millions of people worldwide who suffer from this devastating illness. Let’s hope that research proceeds at a clipped pace to find help for all who need it.