Virtually every new discovery in Alzheimer’s disease treatment is greeted with excitement. In July 2023, the drug donanemab was reported to have slowed the progression of symptoms in early stage patients. A few weeks earlier the FDA gave accelerated full approval to lecanemab. Two months earlier, news came of a rare gene variant, RELN-COLBOS, that appears to protect those who carry it, and of blood biomarkers for astrocyte reactivity that could be used to screen patients to identify those most likely to progress to the disease. Two years earlier, in June 2021, the FDA gave approval to aducanumab, to much fanfare and controversy.
Is the level of excitement accompanying these developments justified? To be sure, they seem promising. Risks of serious brain bleeding and swelling attend the use of all three drugs, though, and the benefits of even the most impressive of them are modest, at best: a four-to-seven-month slower decline in cognition over 18 months for the most optimal patients, with no indication that eventual progression to severe stages is avoided. Effectiveness studies, moreover, often focus on physiological effects associated with the disease that are not actual improvements in the patient’s condition—so-called surrogate endpoints. Amyloid plaques—clumps of beta-amyloid protein in the brain—and tangles of protein within neurons known as Tau tangles are commonly used surrogate endpoints. Some experts are skeptical that amyloid and Tau are key to understanding what causes the disease. Dr Tia Powell, Director of Montefiore Einstein Center of Bioethics, for example, notes that some patients with well-developed Alzheimer’s do not have high amyloid plaque or Tau tangles, and some patients with high amyloid and Tau never develop Alzheimer’s.
The public attention reflects in part the excitement of patients. Jay Reinstein of Durham, NC, for example, age 62 with early-mid stage Alzheimer’s, is enthusiastic about lecanemab: “If it gives me six or 12 or 24 more months at the current level, that’s a great thing.” At the rate of slowdown shown in the tests submitted for FDA approval (noted above), however, Reinstein in 26 months will be where he would otherwise be in 36. That’s not likely to be the “current level” for 6-24 additional months that he imagines.
Hope is good, but how realistic should it be? Should it add to research institutes’ leverage in gaining funding, and pharmaceutical companies’ ability to obtain approval for very marginally effective new drugs? Widespread fear of a disease can be the springboard to determined and constructive effort, but it can also lead to less rigorous, careful assessment. More important is that in the meantime, realistic approaches that can already benefit patients may get overlooked.
“In supported decision-making, trusted others assist persons to still make their own decisions, preserving the dignity of self-determination.”
Live better with dementia
The sensitive and perceptive kinds of care developed in specialized centers like the Penn Memory Center could be more widely used. An element in this approach is “supported decision-making,” a supplement to the guardianship and surrogate decision-making used for those who have lost this capacity. In supported decision-making, trusted others assist persons to still make their own decisions, preserving the dignity of self-determination. Such elements should be standard-of-care.
Opt out of life with dementia
In addition to living better with whatever level of dementia one has, people can do something more definitive to avoid living to its most advanced stages. That future is what many fear most—years of lingering, withering life when one only weakly communicates with others (if at all), does not recognize one’s closest loved ones, and is no longer capable of anticipating tomorrow, or remembering yesterday when tomorrow comes. To many, a life that ends like that is for them worse than if they simply did not live that long. With or without those years, this life is their life. This subjective value underlies the self-determination at the core of the doctrine of informed consent, including the right to refuse lifesaving treatment.
Yet it is difficult for people with progressive dementia to exercise this right, for when they get close to severe dementia, they are not likely to have the capacity to make medical decisions. Fortunately, there are two feasible ways around this.
Withhold life-sustaining treatment by advance directive
Advance directives have been well established morally and legally for decades. When still capable of making such a directive, a person can instruct their healthcare agent and providers to withhold life-extending care when they reach a certain stage of dementia. They can also instruct them to withhold such care somewhat before that stage if it is possible that no such life-threatening condition is likely. By such instructions they can significantly reduce their odds of reaching a stage they badly want to avoid.
Such a strategy using advance directives to refuse treatment is legal, but it has a clear drawback: not everyone is presented with the opportunity to refuse life prolonging treatment. Another course of action, though, is available.
Voluntarily stop eating and drinking (VSED)
Relatively unknown, VSED is a legal way to hasten death when no illness provides the opportunity to die by refusing lifesaving treatment. When well supported, it provides a peaceful and reasonably comfortable death in 7-14 days. It is certainly not for everyone, requiring considerable determination to get through the hunger of the first 36-48 hours (after which hunger dissipates) and after that, to endure the dry-mouth and thirst that do not as readily dissipate. Good palliative measures, though, can help immensely. For those who are sufficiently determined not to live longer, VSED is a viable option.
The problem in the case of Alzheimer’s, however, is that once people lose executive function, they will not be able to carry out VSED. To avoid that, they must do VSED “preemptively,” significantly before executive function and decision-making capacity are lost. They will need to begin VSED when they are still assured of their capacity, and by doing that they are likely foregoing some time worth living.
Such preemptive VSED may sound extreme, but there are well-documented cases of it (and undoubtedly many others). To be sure, the person would give up some valuable time they would liked to have had, but they avoid what they fear most, years of severe dementia.
These last two ways of dealing with Alzheimer’s are seldom acknowledged in the public discussion (or by providers and caregivers). The Alzheimer’s Association does not mention, much less highlight, them. The headlines go to every new treatment, no matter how marginally effective. Some lines of research from those treatments may indeed pay off decades down the road, with huge benefits for humankind, but let’s not fail to attend to the things that people with progressive dementia can realistically do already through taking ownership of the real choices they can make about how their lives end.
Featured image by Christina Victoria Craft via Unsplash, public domain