This morning we talked about Alzheimer’s disease is a thief that robs millions of their memories, their independence, and ultimately, their lives.
As one of the most devastating conditions of our time, it’s no surprise that researchers and pharmaceutical companies have poured billions into finding a cure or at least an effective treatment!
But despite decades of research and countless promises, mainstream medicine seems to be no closer to cracking the Alzheimer’s code.
And the latest string of failures from Big Pharma’s much-hyped Alzheimer’s drugs has left patients, families, and doctors feeling frustrated and betrayed.
But what’s really happening behind the scenes? And why are we constantly running into road blocks? Let’s have a look.
The Disappointing Reality of Alzheimer’s Drugs
In recent years, pharmaceutical giants like Biogen and Eli Lilly have touted their new Alzheimer’s drugs as potential game-changers. These medications, such as aducanumab and donanemab, target amyloid plaque, the sticky buildup in the brain that’s long been associated with the disease.
The theory was simple: remove the plaque, slow the cognitive decline.
But as the clinical trials unfolded, the reality proved far less promising.
While the drugs did succeed in reducing amyloid plaque, they failed to deliver any meaningful improvements in patients’ symptoms. The cognitive benefits, if any, were so small that doctors wouldn’t even notice them in a clinical setting.
Even more concerning, these drugs came with a host of potential side effects, including brain bleeding and swelling. In some trials, up to 37% of participants in the treatment group experienced these adverse reactions.
The Amyloid Plaque Paradox
So why are these drugs falling short?
The answer may lie in a fundamental misunderstanding of Alzheimer’s disease itself.
For years, researchers have focused on amyloid plaque as the smoking gun behind Alzheimer’s. But as Stanford neurologist Mike Greicius, MD, points out, this singular focus may be misguided.
While amyloid plaque DOES accumulate in the brains of Alzheimer’s patients, it’s not always a reliable indicator of the disease’s progression. Many people develop plaque without ever showing signs of cognitive decline, and the deposits tend to form between nerve cells rather than within them.
In contrast, another type of deposit called neurofibrillary tangles, composed of a protein called tau, seems to be more closely tied to the actual damage and destruction of brain cells. These tangles form inside the nerve cells and strongly correlate with the memory loss and cognitive impairment that define Alzheimer’s.
The Placebo Problem
Another issue plaguing Alzheimer’s drug trials is the placebo effect. In a well-designed study, participants are randomly assigned to receive either the actual drug or a placebo, with neither the patients nor the researchers knowing who got what until the end.
But in the case of these amyloid-targeting drugs, the side effects may have unintentionally unblinded the trials. When participants experienced brain bleeding or swelling, they likely figured out they were receiving the real drug, which could have inflated their perceived benefits.
To worsen matters, some trials may have inadvertently skewed their results by removing participants who experienced these side effects from the treatment group, while keeping those with a genetic predisposition to Alzheimer’s (and a worse prognosis) in the placebo group.
So where do we go from here?
While the failures of these amyloid-targeting drugs are disheartening, they also present an opportunity to rethink our approach.
Instead of fixating on a single target like amyloid plaque, we need to take a more holistic view of the disease. This means exploring other potential contributors, such as inflammation, vascular health, and lifestyle factors like diet and exercise.
It also means being more transparent about clinical trial data and allowing outside researchers to analyze the results independently. Only by working together and considering all the pieces of the puzzle can we hope to make real progress against this devastating disease.
For those living with Alzheimer’s and their loved ones, the lack of effective treatments can feel like a betrayal. But it’s important to remember that every failure brings us one step closer to understanding this complex condition.
P.S. Click here to learn more about the silent Alzheimer’s—when your brain hides the signs.
Sources:
Dementia medication side effects | Alzheimer’s Society. (n.d.). Www.alzheimers.org.uk. https://www.alzheimers.org.uk/about-dementia/treatments/dementia-medication/dementia-medication-side-effects
Digma, L. A., Winer, J., & Greicius, M. (2024). Substantial doubt remains about the efficacy of anti-amyloid antibodies. Journal of Alzheimer’s Disease. https://doi.org/10.3233/JAD-231198
