Monday, August 23rd, 2010
Here’s an interesting article in the New York Times about the failure of one of hundreds of drugs designed to slow the decline of Alzheimer’s. Eli Lilly recently halted their extensive and expensive trial of semagacestat becaue the drug was actually making patients worse.
Lilly spent hundreds of millions on this drug, the Times reports—and it is one of hundreds of experimental drugs attempting to lower the accumulation of beta amyloid, a toxic protein, in the brain.
The trouble is, we don’t know for sure that this is what causes, or helps to cause Alzheimer’s. The Times quotes a researcher who explains that we don’t know what the drug targets for Alzheimer’s disease are. “We don’t know because we don’t know the causes of Alzheimer’s.”
Advances have been made recently in tests (PET scans of amyloid plaques, and cerebrospinal fluid tests) that detect amyloid accumulation well before the appearance of Alzheimer’s symptoms. Sitting on the beach recently with LL, my daughter-in-law, I suggested that I’d probably be a good candidate for such tests. I’m 67, and both my father and my mother’s mother had some kind of dementia, so it’s on both sides of my family. LL, who’s a savvy GP, said, “But why would you want to? They might diagnose it correctly, but they can’t help you.”
I wasn’t really considering such tests, it was just a notion. I remain both fatalistic and optimistic. I see no reason to worry right now—but in the long run it doesn’t look good for most of us. If we live long enough, the likelihood of some dementia is large.
I go back often to Peter Whitehouse’s book, The Myth of Alzhehimer’s. (You can read a review of it on the Sidebar page, Other Alzheimer’s Memoirs—even though it’s not a memoir.) Whitehouse, one of the original and influential researchers of the disease, points how how long we have been studying dementia, and how little we are absolutely sure of. As Whitehouse puts it (this is from my review), “most people in the Alzheimer’s empire know that ‘there is no singular disease called “AD,” and that it is a complex, scientifically imprecise social construct that may never be cured.’ And because of this, we would do better to focus our efforts on enlightened care than to pour all our money and attention into finding a cure for this little-understood disease—if indeed Alzheimer’s is a disease at all, rather than simply an effect of brain aging.”
The failure off the Lilly drug, semagacestat, is another setback in a vital field of study. I’m hoping for better discoveries, but so far I remain fatalistic about a stunning chemical solution.
At the same time, I’m never fatalistic about what caregivers can do. Every day, in a hundred ways, a caregiver can do a better job, can make things easier, can lift up those who are declining and dying.
Monday, August 16th, 2010
I’ve read a hundred articles and books about dying. The best of them all is Atul Gawande’s piece in the August 2nd New Yorker, “Letting Go,” in which he writes about the choice that must sometimes be made between fighting to stay alive (or keep a patient alive), and accepting an approaching death.
Gawande is brilliant. I called up his father here in Athens, Ohio (Ram Gawande was my urologist before he retired) to tell him I think his son is a genius, and to ask how Atul managed to write one fascinating article after another for the New Yorker, even as he carried on a full surgical practice in Boston. “He’s very busy,” Ram said.
Busy and focused and the best medical writer we have. “Letting Go,” subtitled “What should medicine do when it can’t save your life?”, is subtle and painful. At the heart of it is that meeting (if it ever occurs), in which a doctor tells a patient that there is nothing that can be done to help or cure his disease. That almost no hope remains.
Of course there is always some hope. Miracles have happened, and we’ve all heard stories about them. The problem is that in pursuing yet another chemotherapy regimen or series of radiation treatments, we sometimes overwhelm the patient, keep her in the hospital when she might be at home with her family, make her last days a nightmare of mechanical ventilators, electrical defibrillations and feeding tubes. As Gawande writes:
“Spending one’s final days in an I.C.U. because of terminal illness is for most people a kind of failure. You lie on a ventilator, your every organ shutting down, your mind teetering on delirium and permanently beyond realizing that you will never leave this borrowed, fluorescent place. The end comes with no chance for you to have said goodbye or ‘It’s O.K.’ or ‘I’m sorry’ or ‘I love you.’”
You can read the full article here.
Most affecting in Gawande’s writing are the stories of his own insecurity, the awkwardness of having that painful discussion with a terminally ill patient. When he does what we might consider the “right” thing, it may not work. From a transcript of questions readers asked of him about the article, I found this additional story, in which Gawande admits that discussions about death don’t always work out well:
“I broke the bad news of an incurable and rapidly aggressive cancer to a patient of mine recently. I tried to think about the best ways to frame it. I said, the clear option to give her a chance of a lottery ticket, of actually controlling the cancer, would be chemotherapy and radiation. But then I said the hard thing, which was [that it is] rare for people to live more than a year or so. If she proved to be one of them, we would dance in my office. But we also needed to think about what was most important to her if she wasn’t one of them.
“When I talked to her a day later, she was angry with me. She told me she read on the internet about people who were cured and they said not to listen to the doctors.
“I didn’t sleep very well that night. I had hurt the trust she had in me. And suppose I was wrong? But then a week later, when we talked again, she was grateful. She pushed ahead with further opinions and then treatment, but I think we are also beginning to think about the limits of what she wants to take as this goes along.”
This is surely one reason that doctors don’t want to tell the truth: it takes hope away from patients, and it can anger them. But to sugar-coat the facts, or simply not report them, and to let terminally-ill patients believe there is much greater hope than science can allow, might result in another patient withering in an ICU instead of making his peace at home with death and his family.
My own father died without ever talking about his death. But then, that was his choice—compounded by a dementia which left him unable to say anything near the end. My girlfriend, Jan, who died three summers ago, didn’t want to talk about death either. Not to me, and not, that I heard, to anyone else. The result was that she was taken to the hospital one day with a failing kidney, suffered some small strokes (they showed up later on either a CT scan or an MRI), and was unable to say more than a few words in the last week of her life. Her family and friends gathered, a world was created around her hospital bed, she underwent test after test. Her brother and I made a move, at the very end, to get her into a hospice center in Columbus, but by then it was too late.
I’m sure many caregivers feel the way I did with both Jan and my father: unsure about pressing someone else to talk about their own death. But I’m also sure of this: I wish everyone would read Atul Gawande’s article, which is a huge step toward an open discussion of how we want to spend our last days and hours.
Sunday, August 8th, 2010
I’m back at my dad’s house, sleeping in the same little room where I lived for the last year of his life. Things have changed, of course. My family is here (or most of us), and off we go to the beach, we go kayaking, we play badminton and cook dinners on the grill.
But in this house my father is never far from my mind. This is the place of Alzheimer’s. Here is the lift chair he sat in, the bed he lay in. Here is where he retreated from the world.
I can take, at times, a somewhat-cheerful stance on Alzheimer’s. I can think about the true connection I made with my father in that last year. But here in his house, what I most remember is how he retreated from life, how it defeated him, how he lost interest in everything.
Talking to a woman from the local paper, I hear the same story about her grandmother. This is the story I’m always alert to: of an Alzheimer’s patient, once lively and inquisitive, who no longer wants to do anything, who now just sits in a chair, who resists all efforts to keep her involved with other people and the world. Perhaps it’s because I’m alert to it that I hear this story so often—but it’s the story I can’t escape, the one that pins me like a bug to a cork board.
Life at its best is filled with will power, with drive and curiosity and excitement. Instead of this, what overcomes so many Alzheimer’s patients is a kind of endemic, untreatable depression. Prozac or other SSRIs might lift an edge of the blanket, but in my father’s case the loss of interest in the world seemed vast and incurable. To forget names and people, to lose track of his own history was painful to him. But what it led to was worse: the time he spent with what seemed a determined will to do nothing. He didn’t want to be roused. He wanted only to sink. It was terrible for him, hence terrible for me—and it’s the story I hear from one caregiver after the next.