Aducanumab, continued…

Today, Harry Johns, the CEO of the Alzheimer’s Association, which has supported the controversial new drug, Aducanumab (Aduhelm), responded to some questions from STAT.  The reason the drug is so controversial is that there is very little evidence that it actually works, if by “works” you mean that is improves cognition or functioning, even temporarily.   That is why the FDA advisory committee voted unanimously against approval.  There is some evidence that the drug may reduce the amount of amyloid junking up the person’s brain, but the connection between amyloid load and symptoms is not well understood.  Some people with lots of amyloid have no symptoms, and vice versa.  In the same way that we want a statin to reduce actual cardiac events, not just cholesterol numbers, we want an Alzheimer’s drug to reduce Alzheimer’s symptoms, not just a biomarker.  In light of that, Johns’s remarks are truly concerning.  In answer to the question, How should patients and families view Aduhelm?  He said:
“We want people to understand that it can make a difference for them, but we don’t want them to think it is going to absolutely change their course, but it is the first treatment that changes the course of underlying disease, rather than just symptoms.” 

Just symptoms???  Just symptoms???  Aren’t symptoms the whole point??? 

Aducanumab: A Family Member’s Perspective

For those who have been following the aducanumab story, here is my essay, posted on the Hastings Center’s Forum:

Aducanumab has just been approved by the Food and  Drug Administration to slow the progress of Alzheimer’s disease. It is likely that many people who are candidates for the drug will no longer be competent to make their own health care decisions, and will be relying heavily on others to make the decision with them or for them.  As a layperson, how would I evaluate the risks and benefits of this drug, were I acting as a health care proxy for someone with Alzheimer’s disease? 

A number of years ago, when my mother was in the middle of her 10-year decline into dementia, her physician wanted to give her Aricept (donepezil) and was very unhappy when I turned it down. At first it had seemed to me that anything was worth a try. There was  evidence that some people experienced small, temporary benefits in cognitive function and activities of daily living.  On the other hand, my mother had problems swallowing pills and hated to take any medication.  Her caregiver was reluctant to coax my mother to take yet one more pill. Side effects included nausea, vomiting, weight loss, dizziness, diarrhea, drowsiness, weakness, trouble sleeping, shakiness, and muscle cramps. My mother already weighed about 90 pounds soaking wet, so even minor weight loss was a worry. Dizziness meant higher risk of falls. Intestinal distress, for someone who was already upset about the loss of dignity associated with bathroom issues, seemed like a really bad idea. All of this might have made sense for someone willing to take on the risks and downsides for the sake of the possible benefit—but my mother could hardly be called willing, as she no longer understood cause and effect. 

My mother is long gone, but I thought of my decision on Aricept when the FDA announced its approval of aducanumab. How would I decide whether to have this drug prescribed for a family member?  I am pretty sure I would say no. And that is assuming that there was a choice: at over $50,000 a year, it is not clear who will be able to pay for it. I would ask myself: does the drug work? What are the risks? What are the side effects?  And how would taking the drug affect the overall quality of life of someone with Alzheimer’s? 

First, it is not at all clear that the drug works, in terms of affecting cognition and slowing decline. As Jason Karlawish explains in an incisive piece in STAT, crucial scientific steps were missed, and the current data are inconclusive and contradictory. 

Side effects include possible brain swelling and bleeds (which appear to be severe in about 6% of patients), headache, falls, diarrhea, and what Biogen describes as “confusion/delirium/altered mental status/disorientation.”  Wait a minute!  I thought the reason to take this drug was that one already had altered mental status and confusion.

Before someone is even considered eligible for aducanumab, they must take a PET scan to ascertain that they have elevated levels of amyloid and then an MRI to make sure they don’t already have brain swelling. MRIs have to be repeated regularly while people are on the drug. I know perfectly competent adults who are freaked out by MRI’s.  How do you explain this to someone with dementia?  Or do you sedate them, thus adding to the risk? Furthermore, the drug itself is not a pill, but a monthly infusion. 

Put that all together, and it just doesn’t add up. How would my mother’s life change for the better? There is little evidence of the drug’s efficacy. Meanwhile, her peaceful life in her rural home with her dedicated caregiver would now be punctuated by trips to the hospital for MRI’s, and monthly struggles to start infusions in her 90-year-old body, with its tiny veins and paper-thin skin. Aducanumab is apparently best suited to people in the early stages of Alzheimer’s, but even in the earliest stage my mother refused to accept that she had a problem. I cannot imagine successfully explaining that we were taking these measures in the faint hope of combatting a problem she insisted she didn’t have. And in the absence of an explanation she could understand, surely the frequent hospital trips would feel to her like unpleasant, even scary, invasions.

Like most people with a family member with dementia, I would have crawled on my knees over broken glass to get access to something that helped, even if that help was merely to slow down the inevitable.  Sadly, aducanumab is not that help. I just hope that all the family decision-makers out there can resist the pressures of guilt, hope, desperation, and the need to do something, that they will take a deep breath and decide what is best for their loved one.


This week’s JAMA has an article “General Health Checks in Adult Primary Care.”  There has been some controversy around whether the “annual physical” is really useful.  It doesn’t seem to have an effect on, e.g., mortality, but many doctors argue that the benefits in trust and understanding are important, if not measurable. 

But what struck me was, that under “Potential Adverse Effects,” it said: “Four randomized trials demonstrated potential adverse effects of general health checks. In the A Healthy Future trial, which examined a preventive services benefit package for Medicare beneficiaries, participants in the intervention group 75 years or older, compared with those 75 years or older who received usual care, had increased mortality over 2 years.  A follow-up analysis attributed this finding to increased completion of advance directives and decreased receipt of unwanted life-sustaining treatment in the intervention group.”

In other words, if the directive does its job and wards off unwanted life-sustaining treatment, that’s an adverse effect!  I wonder if the editors even realize how ridiculous that sounds!

Could the coronavirus be today’s “old man’s friend”?

William Osler is famously quoted as calling pneumonia “the old man’s friend,” because it provided a relatively swift and painless death. Today, however, pneumonia has become just one more enemy in our unrelenting and often thoughtless pursuit of longer life. A 2007 Harvard Health letter reports, with no discernible irony, that Osler’s comment “was over 100 years ago. Today, vaccines, antibiotics, and improved supportive care mean doctors can do a lot more about pneumonia.”  Goodbye, old friend.

Recently, I gave a talk about Alzheimer Disease at a medical school.  There were about 80 people in the zoom room and, as I usually do, I began with a thought experiment.  I told them about three people, and then asked them which of these three they would prefer to be.  Marty, as I called him, died suddenly at age 85 of a heart attack, while he was still cognitively competent and living independently.  Sylvia was diagnosed with Alzheimer at age 85, and died of natural causes at age 90, while in the moderate stage of the disease and living in a nice memory care center.  Betty was also diagnosed with Alzheimer at 85, but she lived for ten more years, dying at 95 while in the final stages of severe dementia.  Only one person in the room would prefer to be Betty.  Two-thirds would prefer to be Marty, and one-third Sylvia.  In other words, two-thirds of the people would prefer to die before becoming demented, even if that meant a shorter life, and the final third would prefer to die before the dementia became severe. 

I have given a lot of talks like this, and the numbers always come out more or less the same.  Of course, this is anecdotal evidence, and with academic audiences.  I am currently engaged in a project to ask the same sort of questions with more randomly selected Americans, and I look forward to those results. Meanwhile, I think the responses I get are at the least very provocative. 

There are some published studies that come up with results that can flesh out this picture.  A 1997 study of over 9,000 seriously ill people discovered that 26% were “very unwilling” to live in a nursing home, and 30% would “rather die.”[1]  A 2016 study of seriously ill but cognitively competent people found that a majority believed that either incontinence or “being confused all the time” were states equal to or worse than death.[2]  A 2019 project found that about a fifth of participants who discovered that they had elevated amyloid-B, and thus a higher risk of getting Alzheimer, expressed interest in physician assisted suicide.[3]

In other words, there are a whole lot of us who think that, if we were demented and/or unable to live independently, we would actually prefer death.  Since physician assisted suicide is not available to people with dementia, it seems that “the old man’s friend” could be a welcome visitor.  Could the novel coronavirus be today’s old man’s friend?   

This is an important question right now, as society grapples with how to allocate vaccines against the virus.  The idea that someone suffering from dementia and confined to a nursing home might actually welcome death is apparently so taboo that it cannot be openly contemplated. 

A recent study from Careport Health


found that “in the nursing home population, dementia appears to be associated with a 1.7x risk of death, even after adjusting for age.”  The response, of course, has been—let’s get those people vaccinated!  But what about informed consent?  Given the results I have laid out above, it appears that many, perhaps the majority, of people, would rather die than live in a nursing home with dementia.  For them, refusing a vaccine is the logical thing to do.  Of course, because they have dementia, they are no longer capable of logical thinking.  But if they had taken the trouble, while competent, to appoint a healthcare proxy and communicate their wishes clearly, it should be obvious to the proxy that they would not want the vaccine.

I understand that, because vaccines protect others as well as ourselves, this is a more complicated question.  I am one who would rather die than live in a nursing home, and I would certainly rather die than live with dementia.  So, if I were incarcerated in a nursing home in the earliest stage of dementia, while still capable of making decisions, I would definitely refuse the vaccine and embrace deliverance via Covid-19 with open arms.  That does, of course, put others at risk, including underpaid, dedicated healthcare workers.  But then the best use of these precious vaccine doses is to put them in the arms of the healthcare workers, not in the arms of residents who may not want them.

[1] Mattimore, TJ, Wenger, NS, Desbiens, NA, Surrogate and Physician Understanding of Patients’ Preferences for Living Permanently in a Nursing Home.  Journal of the American Geriatric Society 1997 July; 45(7):818-824.

[2] Rubin E, Bueller AE, Halpern, SD. States Worse than Death among Hospitalized Patients with Serious Illnesses. JAMA Internal Medicine. 2016 Oct; 176(10):1557-558.

[3] Largent EA, Terrasse M, Harkins K, Sisti DA, Sankar P, Karlawish J. Attitudes Toward Physician-Assisted Death From Individuals Who Learn They Have an Alzheimer Disease Biomarker. JAMA Neurol. 2019 Jul 1;76(7):864-866.

Vaccine Distribution and Racial Equity

Most Americans know that African-Americans have a significantly lower life expectancy than White Americans. Most of us don’t think through the implications of that disparity. For example, all working people pay into Social Security, but African-Americans are less likely to live long enough to collect it. In this op-ed, published today in the Allentown, PA Morning Call, my colleague Tom McAndrew and I explore the implications of that racial gap for allocation of the Covid-19 vaccine. We point out that, if we allocate vaccines primarily by age, African-Americans will be seriously underrepresented.

The Plug

The Plug is a brief video created by Marije de Haas. De Haas and her collaborators call this “design fiction.” The context is European, where euthanasia is legal in some countries, but where advance directives for euthanasia in the case of dementia are rarely honored.

The idea is that the plug is kind of a reverse pacemaker. It is inserted into your body, where it self-activates to end your life when certain conditions obtain. The video doesn’t explain what those conditions might be, but we can imagine them from the stages of Alzheimer Disease. Assuming you would want the plug at all, would you set it to activate when you lost control of your bowels and bladder? When you could no longer live independently? No longer recognize family? Mostly bedbound and with little or no power of speech? Remember, you are making a decision now, as a competent person, for something to happen later when you are not competent. Are you willing to risk the possibility that when the conditions you set up obtain, you might be demented but quite happy? Are you willing to risk now that you might deprive yourself of some demented but pleasant life later? After all, you will be demented then, and you won’t remember you have the plug, or know how to deactivate it.

I found out about the video when Marije got in touch a few years ago, asking permission to use my language from a 2014 article to create a speech for her main character, “Sabrina.” In the end she used it virtually word for word. I was delighted to have my words put into the mouth of such an attractive and fashionable character!

Should Age be a Criterion for Triage during the Pandemic?

Yeah, I know I said in an earlier post that we spend way too much time obsessing about ventilator triage–something that has never happened in America so far–and not enough time obsessing about why our health care system is so broken. Nonetheless, with my friend Felicia Nimue Ackerman, a philosopher at Brown University, I made a brief video on the topic, for the Aging & Society conference. I kind of like my last point, which I have not seen anyone else make. It comes out of an experience my family suffered in 1985, when my thirteen-year-old cousin was killed in a plane crash. That taught me the difference between sadness and tragedy.

Coronavirus Contact Tracing

For three years during the 1960s, I worked for various organizations, all of us trying to end the War in Vietnam.  At one point, I was employed by the Fifth Avenue Peace Parade Committee, while my boyfriend worked for the Student Mobilization to End the War in Vietnam (affectionately known as “The Mobe”).  Both of these groups were coalitions of organizations that came from various perspectives, everything from Trotskyite to pacifist, but all with the common purpose of ending the war.  Or so we thought.

As time went on, we became increasingly frustrated with our inability to work collaboratively; it seemed like we spent more energy squabbling with each other than in fighting against the war.  The sense of guilt and failure dogged me for years.  Had we really been so immature that we let petty differences get in the way of our goal?  Did we really care more about who marched first in a parade, than about saving children from napalm?

It wasn’t until 1986, when the Socialist Workers Party won a tort case against the Dept of Justice and the FBI, that I fully understood how the FBI had used hundreds of informers and agents to not only spy on coalitions, but to actively seek to disrupt them.  They sent obscene letters to set one group against another, tried to foment violence at peaceful demonstrations, and posed as employees of antiwar groups.  From the agency that tried to drive Martin Luther King, Jr. to suicide, I suppose this is no surprise.  But even decades after it happened, I was shaken to discover that colleagues whom I had liked, whom I had eaten lunch with five days a week, were really agents whose purpose was to frustrate every goal for which I was working.  I hadn’t even known them by their real names.

Why am I thinking about that now?  A couple of weeks ago I watched an excellent Hastings Center webinar on digital contact tracing for Covid-19.  There are various ways to do this, but the best seems to be an app on our phones that records where we have been and with whom we have been in close proximity.  If someone reports getting sick with the virus, everyone who has been close to them can be traced and tested.  As Ed Felten explained, “Everyone’s phones keep records, and various companies keep records, of exactly where we’ve been, based on GPS and other location finders.  You could then take people’s location histories and match them against each other and if you see that two people have been in the same place at the same time, you would know there was a possible exposure.”

The presenters are really smart people, and it sounds pretentious and condescending to call them naive.  And yet their faith that we could prevent this information from being misused, was astounding to me. In order to place such an app on my phone, I would have to believe at least the following things: that the promised anonymity would be respected; that the government would not get hold of it; that it would not be used to trace contacts for other reasons, e.g., to discover an immigration lawyer’s clients.  (Do you remember when we discovered that Uber’s passenger app not only traced you to your destination, but continued to trace where you went after you exited the car?)

As the other discussant, Ryan Calo, noted, we would need important safeguards against mission creep, whereby the surveillance app did not de-activate just because the pandemic was over.  Perhaps the government discovers a new use for it; perhaps we kind of get used to it, the way we are used to the idea that our EZPass keeps a record of every toll booth we have gone through, and our grocery store loyalty card keeps a record of the foods we buy.  Calo noted that “clear, explicit rules are critical,” but what point are rules if the government clandestinely subverts them?

There are a lot of things I do to participate in the fight against Covid-19.  I wear a mask faithfully, have not gotten a haircut in months, teach via zoom, and haven’t hugged my own son.  I have volunteered for a vaccine trial.  But for me, this is a bridge too far.  I have noticed speculation that the “boomer” generation wouldn’t adopt this technology because we are less comfortable with tech.  Maybe we won’t adopt this technology because we have long memories.

Running to Tarshish

The New York Times corroborated something I have long thought to be true: no one who has suffered from the novel coronavirus in America has been denied a respirator due to scarcity.  That being said, why has so much energy and rhetoric been spent on the topic of ventilator triage?  Ventilator scarcity and the looming prospect of triage was a leitmotif of almost every Cuomo news conference in the early days.  The Hastings Center Forum, an edited blog on bioethics, had numerous essays on denying people scarce ventilators due to “ageism,” ‘ableism,” racism, and their DNR status.   All this talent and energy focused on something that never happened.  Why?

I think the answer has something to do with a bioethics syndrome my friend and fellow bioethicist Laurie Zoloth called “running to Tarshish”, from the Book of Jonah.  Jonah, we recall, was a biblical figure who was called on by God to go to Nineveh, and tell the people there to repent.  Jonah didn’t want to do that, because he knew that the people would indeed repent and God would spare them.  Jonah thought the Nineveh inhabitants were a bad lot and he had no interest in saving them.  Instead, Jonah turned in the other direction and booked passage on a ship headed for Tarshish.  We know what happened then: God causes a terrible storm, the sailors throw Jonah overboard, and he is swallowed by a giant fish.  Jonah repents, the fish disgorges him, and he takes on the original task.  He goes to Nineveh to warn them of God’s anger if they do not change their ways.  The people do repent and God has mercy on them.  Jonah, meanwhile, is sulking under the meager shade of a gourd vine, which God has caused to grow.  When God kills the vine, Jonah is furious, not to mention in imminent danger of sunstroke, so furious that he asks to die.  God says: “Thou hast had pity on the gourd, for which thou hast not laboured, neither madest it grow, which came up in a night, and perished in a night; and should not I have pity on Nineveh, that great city, wherein are more than sixscore thousand persons that cannot discern between their right hand and their left hand, and also much cattle?”  (I love God’s grasp of the practical–don’t forget to mention the cattle.)

Laurie’s point was that bioethicists “run to Tarshish” by focusing on sexy and speculative issues and turning from the difficult, systemic ones.  As I recall, she was talking about our propensity (herself included) to be fascinated by the pros and cons of advances in genetics, which at that point had helped very few people, while paying too little attention to access to health care, food deserts, poverty and the like, all of which we have the technical ability to fix now.

Obsessing about ventilators is an example of running to Tarshish.  It’s an easy problem to think about, the kind of thing one would put on an ethics exam.   There are 5 ventilators, and 6 people of various ages, occupations, and states of health: how do we choose?  Be sure to defend your choice.  It also suggests that the necessity for triage is a neutral fact, not itself a communal choice to spend less money on healthcare and more on the military.

So instead of running to Tarshish, maybe we should be thinking more about why we don’t have enough ventilators.   Or why such an outsize proportion of virus deaths occur among people of color.  Or the best way of getting universal access to healthcare.