Finding Clarity in the Alzheimer Disease Treatment Landscape

Written by: Eric Wang, Senior Medical Writer (he/him)

Alzheimer Disease is currently the sixth leading cause of death among US adults and the fifth leading cause of death among adults aged 65 years or older.1 For many of the estimated 6.5 million Americans currently living with Alzheimer Disease,2 living can often feel unforgiving. Alzheimer Disease strips away the very elements that make you who you are: your personality, your memories, your stories, your experience, your energy, your interest in hobbies, your ability to communicate, and even your ability to navigate your own home.

While it may be difficult to face the oftentimes heartbreaking reality of this disease, talking openly about Alzheimer Disease, its distressing effects, and its impact on caretakers is vital to reducing the stigma associated with this condition. Opening an honest dialogue also helps generate the urgency and emotional fortitude needed to fund research to find effective Alzheimer Disease treatments.

As a patient with Alzheimer Disease, your whole life is shrouded in uncertainty. You think the woman sitting next to you is your daughter, but you can’t be sure. You haven’t bathed in days, yet you can’t muster the courage to step in the shower. You feel helpless as you can’t control your bladder or bowels, can’t clean yourself, and can’t feed yourself. Often, you struggle to find the strength and confidence to press on.

More than a century after German pathologist Alois Alzheimer first identified this disease in 1906, we still know precious little about this disease. For questions like “how does Alzheimer Disease work?” or “how does Alzheimer Disease develop?”, all we have are educated guesses. After all this time, why do we still know so little about this disease? 

Despite extensive scientific efforts and expensive clinical trials, countless medications have failed to reverse, stop, or even slow the progression of Alzheimer Disease. In 2021, there was a brief glimmer of hope as Aduhelm was FDA approved for the treatment of Alzheimer Disease. There was much fanfare surrounding this approval, as Aduhelm was the first Alzheimer Disease treatment approved since 2003 3; however, even the FDA was skeptical about Aduhelm’s actual clinical benefit.4 All told, more than 200 investigational Alzheimer Disease programs have failed or have been scrapped in the last decade.3

Amid all this failure and confusion, on July 21, Science published a bombshell of an article that shook the Alzheimer Disease world. The article details how Dr. Matthew Schrag uncovered that a pivotal study, which has greatly influenced the trajectory of Alzheimer Disease research over the last 16 years, was based on falsified results.5 Schrag argued that the suspect work “has been cited … thousands of times and thus has the potential to mislead an entire field of research.” 

The suspect article supported the controversial “amyloid hypothesis,” currently the dominant model for explaining how Alzheimer Disease develops and for guiding the development of potential Alzheimer Disease treatments.6 According to this hypothesis, beta-amyloid, a sticky compound that builds up in the brains of Alzheimer Disease patients, activates the immune system and triggers inflammation that destroys brain cells, causing the signs and symptoms of Alzheimer Disease. While the amyloid hypothesis remains plausible, some Alzheimer Disease experts believe this researcher’s alleged fraud may have misdirected Alzheimer Disease research for over a decade and a half.5

Shockingly, this kind of dishonesty is not uncommon, even in peer-reviewed scientific literature. Thirty-four percent of researchers admit to engaging in “questionable research practices,” and, furthermore, 72% of those surveyed know of colleagues who had done so.7 Research results that are negative (unsuccessful) tend to be under-reported, while results that are regarded as positive (successful) tend to be over-reported.8 In fact, for every 1 positive result in the published world, there may be 19 negative counterparts left unpublished.9 Every year, an estimated 12,000 clinical trials that should have been fully reported are not.8 As a result, researchers can’t benefit from relevant past research, impeding scientific progress.

With the mounting failures in the Alzheimer Disease treatment landscape, it is easy to feel discouraged. Undoubtedly, Alzheimer Disease is a complex, multifactorial disease, and one that we are just beginning to understand; however, despite our limited understanding of how Alzheimer Disease slowly devastates millions of lives, there is reason for hope.

Despite all the failures and setbacks in the field of Alzheimer Disease research, the silver lining is that the failures are well-reported. As a result, researchers can learn from other researchers’ failures. Future research can avoid the pitfalls of studies based on assumptions from previously falsified results, and the Alzheimer Disease research community can move toward more nuanced and more accurate models of the disease. Armed with this knowledge, those of us fighting for a cure for our loved ones with Alzheimer Disease are increasingly able to navigate the murky waters of Alzheimer Disease research with more clarity.

If you have family or loved ones with Alzheimer Disease, here are some helpful resources:

The Alzheimer’s Association 24/7 Helpline (800.272.3900) is available 24/7, 365 days a year. Through this free service, specialists and clinicians offer confidential support and information to people living with dementia, caregivers, families, and the public.

The Alzheimer’s Association (https://www.alz.org/local_resources/find_your_local_chapter) has gathered a wealth of resources, including an up-to date list of local Alzheimer’s Association chapters you can join.

Alzheimer’s Association Education Center (https://training.alz.org/) offers a number of Alzheimer’s and dementia programs available online, 24 hours a day, in both English and Spanish. 

The Alzheimer’s Association Virtual Library (https://www.alz.org/help-support/resources/virtual_library) is an online resource center devoted to increasing knowledge about Alzheimer's and other dementias

When facing Alzheimer's disease, there are many variables to consider. The Alzheimer’s Association Alzheimer’s Navigator (https://www.alzheimersnavigator.org/) was created to help guide caregivers by creating a personalized action plan and linking you to information, support, and local resources.

ALZConnected (https://www.alzconnected.org/) is a free online community for everyone affected by Alzheimer DIsease or another dementia, including patients, caregivers, family members, and friends.

The National Institutes of Health’s Alzheimers.gov contains a searchable database of Alzheimer Disease-related clinical trials, including information on enrollment (https://www.alzheimers.gov/clinical-trials).

The Alzheimer’s Foundation of America (https://alzfdn.org/caregiving-resources/) provides a wide variety of resources for Alzheimer Disease and dementia caregivers.

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Here at Razorfish Health, we are dedicated to crafting accurate and compelling scientific and medical communications to help innovative companies promote their life-changing treatments. If you are interested in working with us, please reach out to Delia.Pavlichko@razorfishhealth.com. We’re interested in hearing your perspective, as well as your thoughts on communication challenges and opportunities.

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 Sources:

  1. Alzheimer's disease and related dementias. Centers for Disease Control and Prevention. Updated October 26, 2020. Accessed September 14, 2022.

  2. Rajan KB, Weuve J, Barnes LL, McAninch EA, Wilson RS, Evans DA. Population estimate of people with clinical Alzheimer’s Disease and mild cognitive impairment in the United States (2020-2060). Alzheimers Dement. 2021;17(12):1966-1975. doi:10.1002/alz.12362

  3. Yiannopoulou KG, Anastasiou AI, Zachariou V, Pelidou S-H. Reasons for failed trials of disease-modifying treatments for Alzheimer disease and their contribution in recent research. Biomedicines. 2019;7(4):97. doi:10.3390/biomedicines7040097

  4. Cavazzoni P. FDA's decision to approve new treatment for Alzheimer's disease. US Food and Drug Administration. U.S. Food and Drug Administration. Published June 7, 2021. Accessed September 14, 2022.

  5. Piller C. Blots on a field? A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer's articles, threatening a reigning theory of the disease. Published July 21, 2022. Accessed September 14, 2022.

  6. Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608. doi:10.15252/emmm.201606210

  7. Fanelli D. How many scientists fabricate and falsify research? A systematic review and meta-analysis of survey data. PLoS One. 2009;4(5):e5738. doi:10.1371/journal.pone.0005738

  8. Dickersin K, Chalmers I. Recognizing, investigating and dealing with incomplete and biased reporting of clinical research: from Francis Bacon to the WHO. J R Soc Med. 2011;104(12):532-538. doi:10.1258/jrsm.2011.11k042

  9. Nagarajan PJ, Garla BK, Taranath M, Nagarajan I. The file drawer effect: A call for meticulous methodology and tolerance for non-significant results. Indian J Anaesth. 2017;61(6):516-517. doi:10.4103/ija.IJA_280_17

Dan Rivera