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Key points
- Research outcomes and logical reasoning demonstrate that the amyloid hypothesis for Alzheimer's is deeply flawed.
- The cost of attempting to treat the illness with drugs is reducing quality of life for persons living with dementia and their care partners.
- We would be better served by abandoning the disease model of dementia in favor of a disability/rehabilitation model of treatment.
This is a guest post by Cameron J. Camp, Ph.D., Director of Research and Development, Center for Applied Research in Dementia
Regarding the approval of the drug aducanumab for the treatment of Alzheimer's Disease, a post in this space discussed the process and lack of evidence of efficacy for aducanumab, along with the politics of the process. I would like to present an overview of the general hypothesis that amyloid is a cause of what is called Alzheimer’s disease (AD), and the consequences that have been produced by adhering to this hypothesis. As psychologists, citizens, and persons who are aging as well, readers should take note.
There is a widely known phrase “There’s an elephant in the room.” This refers to an obvious (usually unpleasant) fact the people simply choose to ignore. It is a kind of doublethink or cultural blindness, which allows individuals to overlook an obvious threat to widely-held assumptions and thus maintain both the status quo and clear consciences. Unfortunately, for those who wish to hold on with a death grip to the concept of amyloid being the cause of AD, there is not only an elephant in the room but an entire herd.
Problem 1: The first elephant involves the fact that there are individuals with massive amounts of amyloid in their brains who do not show the classic cognitive symptoms of AD. Those who subscribe to the amyloid hypothesis explain this anomaly by saying that such individuals have “cognitive reserve.” This approach confuses naming a phenomenon with understanding its cause. How do we know that a person has cognitive reserve? Because the person has amyloid without cognitive symptoms. Why do they have amyloid without symptoms? Because they have cognitive reserve. Such circular reasoning would cause a graduate student to fail a general exam in psychology. And so, we have persons with amyloid who do not show symptoms of AD.
Problem 2: The second elephant is that there are already cases where a drug has been used to reduce the amount of amyloid in the brains of persons with AD without showing corresponding improvements in cognitive function. This occurred when a vaccine to remove amyloid was tested in the early part of this century. Trials were suspended due to an unintended effect of the drug: swelling in the brain leading to death in some trial participants. Interestingly, some of the persons who survived the treatment later died and had their brains autopsied. The findings were interesting: Amyloid had been reduced, but these individuals did not show corresponding cognitive improvements. Regarding aducanumab, it was approved by the FDA because it was considered to have shown the capacity to reduce amyloid in the brains of persons with AD. Notably, no reports of corresponding cognitive improvement in persons treated with aducanumab have been forthcoming. And so, we have drugs that reduce amyloid and yet do not produce improvements in cognition.
Problem 3: The third elephant involves the “side effects” of drugs used to treat AD. As the data from the aducanumab study show, 40% of persons taking the drug showed brain swelling and hemorrhaging with this treatment. The brain is a complex, interactive biological system with feedback loops. My graduate advisor once told me, “It is not parsimonious to think parsimoniously about non-parsimonious phenomena.” In other words, complex problems do not readily yield to linear, simplistic, reductionistic bottom-up thinking. Amyloid has multiple functions in the brain, and attempts to clear it have generated undesirable results, including death, without noticeable benefits.
Problem 4: The fourth elephant is sociological. The Alzheimer’s Association’s website has a page describing aducanumab as being able to potentially let persons with AD live better and hold on to memories longer, while the same page has a statement that there is no evidence that aducanumab can improve cognitive function. Note that aducanumab has been refused as a treatment by major medical associations in the U.S. and has been denied access to markets in Europe and other countries by their versions of the FDA. What are these organizations seeing that the FDA and the U.S. Alzheimer’s Association are not?
Problem 5: The fifth elephant is economical. The cost of aducanumab was initially $56,000 for a year for this infusion treatment; Biogen’s reduction of the cost to $28,000 a year followed. When the Centers for Medicare & Medicaid Services decided not to pay for the general use of aducanumab, a hue and cry were heard about depriving access of aducanumab to underserved and underprivileged groups (see this essay by Judith Garber of the Lown Institute for a thorough debunking of this claim). When, as a society, we collectively see dementia as a disability rather than a disease and adopt a rehabilitation model rather than a pharmaceutical model for its treatment, we will become more humanized and effective.
Beyond the elephants in the room
There is a herd of elephants in this room, and they are trumpeting and screaming. Must we, as persons concerned with mental health and dementia, continue to behave as if we are blind to them? Will we continue to let the forces encouraging us to ignore the elephants control the national discourse on dementia and its treatment? CMS is closing public comment on access to aducanumab on February 11, 2022. It is time to comment, educate, resist, and maintain the pressure to create change.
