David Shenk (davidshenk) Sun 1 Feb 04 11:52
Yes, and I was happy to have that. But when a magazine seriously considers an excerpt from your book, then assigns a lengthy book review instead, and this is how it turns out, you can imagine the level of ambivalence. I can't tell you the number of people I talked to who read the first two pages of that piece, never got to any acknowledgement of my book, and then said to me, "Hey -- did you see that Franzen has an essay on Alzheimer's in the New Yorker?"
David Gans (tnf) Sun 1 Feb 04 12:12
I hear ya. But you have to figure most people read it all the way through. Or hope so, anyway :^)
Steve Silberman (digaman) Sun 1 Feb 04 14:03
David, sorry I'm late arriving here, but I just wanted to make the point that "The Forgetting" is not only a stunning book because of its subject, but because of its craft. It's beautifully written -- there were many times when the hair on the back of my neck stood on end while reading it, as it did just now when I read the passage about Ralph Waldo Emerson signing his autograph twice, in the final part of the book. I think it's a masterpiece. Granted, I'm not an entirely objective critic, because you and I wrote a book together in the early '90s, as some people here know. But as a writer myself who tackles complex neurological subjects for my work in Wired, I know just how hard it is to make these scientific matters comprehensible to a smart, non-professional reader, while retaining the human force of the story. A superb book, my friend.
Cynthia Dyer-Bennet (cdb) Sun 1 Feb 04 15:59
David, the two types of drugs you mention don't do anything to attack the root of the problem, they simply address the symptoms for a short while. In your book you talk about another whole area of research, where scientists have been looking for something along the lines of a vaccine that could stop the disease before it begins. You also touch on an experiment where scientists were able to actually reverse the build-up of plaques and tangles. Those areas of research seem like they'd be so much more fruitful. What's on the horizon as far as this kind of work?
David Shenk (davidshenk) Sun 1 Feb 04 18:06
Thank you for your staggering words, Steve. You already know how much that means to me. To any others out there who've read the book, whether you liked it or didn't, I'd love to take some time at some point in this discussion to toss around some of its ideas. This will probably sound pretentious, but I really aim to produce work that is as much literature as, say, any well-written novel out there. My heroes are John McPhee, Joan Didion, E.B. White, Truman Capote and others who have raised non-fiction to an art form. I told you it would sound pretentious. Meanwhile, I'm of course very happy to answer science questions as best I can. Cynthia: Yes, indeed, the true excitement behind Alz research lies in the avenues that could potentially slow or stop or prevent the disease. To do this, they think they'll have to stop the formation of the plaques and/or tangles. Actually most researchers strongly suspect that the plaques are the main ones to focus on, that if the plaque material (known as beta amyloid or "a-beta") could be prevented from forming, or dissolved as it forms, the disease could be stopped. (Please don't ask me why plaques are the favorite target right now -- that's a longer story than you want to get into in this forum). Elan Pharmaceuticals' vaccine was the first drug that potentially could eliminate plaques from human brains. The idea of the vaccine was so simple and powerful, it took other researchers' breaths away. They would inject beta-amyloid into human body, stimulating the body to itself form antibodies to that substance, which would then creep into the brain and sweep the plaques away. No one thought it would work -- it was just too simple of an idea, and many thought the blood-brain barrier would not admit such antibodies. But it tested extremely well in mice and a few years ago went into drug trials in humans. Sadly, it stimulated a dangerous immune response in some of the human trial subjects, and a few of them died. So they had to suspend the study. But the data they were able to gather in the early going was extremely promising, and so researchers are racing to come up with a new, safer vaccine so they can try it again. There are other approaches, too, that are just as exciting, and almost as close to fruition. They are also aimed at preventing/removing plaques.
an impressive spasm of competence (tinymonster) Sun 1 Feb 04 18:24
Cynthia Dyer-Bennet (cdb) Sun 1 Feb 04 18:33
> it stimulated a dangerous immune response in > some of the human trial subjects, and a few of them died. So they had > to suspend the study I don't understand that part, actually. The study subjects were suffering from a terminal disease. If I recall the numbers correctly from your book, it was about 2 percent of those in the study who had the bad reaction to the drug and died. Everybody else in the study is going to die of the disease. Why stop it if 98 percent of the people in the study are showing marked improvement?
Cindy (loves2sing) Sun 1 Feb 04 19:17
David, I've heard a LOT of rumors about Alz, about causes and prevention. Some of the most popular: (1) Alz is caused by aluminum deposits in the brain, largely from using aluminum cookware with acidic foods; and (2) Alz is caused by not using the brain, not learning new things, not having stimulating experiences, etc. Are these myths?
David Shenk (davidshenk) Sun 1 Feb 04 19:54
Cynthia: Whoah. I certainly didn't mean to suggest that 98% were showing marked improvement. They probably weren't showing much of anything in the early going. I'm not completely on top of what happened, but the improvement probably showed up (ironically) in autopsies of those who had been killed. Remember, they can't see what's happening to plaques in living brains yet (at least until this Pittsburgh compound was invented). So they have to watch behavior -- very tough thing to measure except over the long term. In any case, I believe it's a cardinal rule that you don't continue with studies of drugs that may kill that many people, even if the disease is terminal. It does open up some interesting ethical questions, but I think that thinking is widely accepted. By the same token, you could ask why they don't take brain biopsies of Alz patients who are taking experimental drugs. They could learn a hell of a lot -- and after all, these people are terminal. But they just don't do it. Cindy: Thanks for raising this issue. It's an important one. I write a lot about rumors and about shysters in my book. Alz is the *perfect* disease if you're a con artist "healer" or a pseudo scientist, because it is so complex and because millions of people are desperate to believe anything that sounds simple and hopeful. So if you look around you see lots of b-s artists telling you what causes Alz, how to cure it with this or that elixir, etc. Some say outright that Alz doesn't exist. Aluminum does not cause Alzheimer's, as far as anyone can tell. It has been found in Alz brains, but that's because the disease has compromised the blood-brain barrier early on and allowed all sorts of crap into the brain that doesn't normally get in. Your #2 is a lot trickier. As stated, it is false. Alz is certainly not caused by lack of use. And there are plenty of brilliant people who get Alz. But what may be true -- they're still not sure -- is that you might be able to push off the onset of the disease, or perhaps slow down the progression of the disease, by living a vigorous and intellectually challenging life. You won't innoculate yourself, or stop the disease in its tracks. But maybe you'll get it a few years later than you would have -- which is a huge deal. Researchers estimate if they can find a way to delay onset by 5 years, they'll cut the number of cases in half -- meaning that half of the people who would have gotten Alz will die of something more merciful in the meantime.
Paulina Borsook (loris) Sun 1 Feb 04 23:30
david, dont know if you are familiar with the slim elegant novel 'moral hazards', in part about watching a loved one go thru alz...anyway, there is a great bit where the caretaker/partner of the alz sufferer is hearing all these news stories about use yr brain/it's aluminum/ take vitamin e/ whatever --- while meanwhile, the homehealthcare workers in the nyc alz community,' by and large a smart but not terribly formallu educated immigrant pop --- think alz comes from too much education. for -they- are taking care of all these former professors/lawyers/docs who have it...i see that in my own life, where one of my mother's best friends, a remarkably active smart fit woman (went back and got her collefe degree at at 65; always had a mad social life going into her 80s; read wiselu and well and are her oat brain and did her yoga) --- got alz. whereas my evil mother, whose idea of exercise consisted of ordering the cleaning lady around and who would have been happy living on a diet of ham sandwiches and chocolate malts, even -after- she was diagnosed with diabetes... in some sense has had a much slower mental decline than her wonderful athletic conscious intellectually engage friend. sigh. istr your book was written -before- all the nNo Longer Take HRT study came out, and one of the side effects of hrt was -now- considered to be alz. i have wondered if the pop now in their 60s -80s, the 1st gen of woman to have been so hormonized, are having some of the uptick in alz because of this. i also seem to recall that women are twice as likely to get alz/dementia?
Paulina Borsook (loris) Sun 1 Feb 04 23:35
and oh, i didnt mean to sound persnickety about pureform alz vs more mixed dementias. simply that i thot they were different diseases, with somewhat different courses (my mother's fits with the rest of her general vascular collapse, small strokes, etc etc). the progression of her illness is not like what i know of pureform alz i.e. she has known for yrs her memory is not what it was, she has physical frailty somewhat matching the mental ga-ga ness, etc etc...
David Shenk (davidshenk) Mon 2 Feb 04 06:53
Paulina, You're right that a study last year of hormone replacement therapy -- estrogen plus progestin -- showed an increased chance of getting Alzheimer's, and demonstrated plenty of other reasons not to pursue hrt. But regarding Alz, the hormonal picture is still very imcomplete. Previous studies have shown that increased estrogen may significantly decrease the chance of getting the disease. So the hrt study shocked researchers and they're still trying to figure out what it means. There was also a recent study that showed increased testosterone reduces Alz risks somewhat. What I take away from all this is: non-scientists should ignore all this stuff. There is no particular road map on how to prevent Alz, other than eating right, exercising the body and the mind, and keeping stress to a minimum -- and even all of that may not make much of a difference. Women do have a *slightly* higher incidence than men -- not anything like double. (I think you may have confused a stat from the hrt study). But in truth, no man can look at a woman and say, "you'll probably get Alz and I probably won't." Each one of them runs a risk that will closely correspond to how long they live. I haven't read Moral Hazards, but I like the point very much. There are so many examples of the supposedly smarter half of a couple getting Alz -- and so many of the converse. You just can't tell. Ed Markey, the Congressman from MA who leads the fight for Alz funding on Capitol Hill, likes to convey to people his dismay that his hyper-intellectual math whiz mom got Alz while his working class, mildly-educated Dad did not. Ronald Reagan got Alz, but so did Ronald Reagan.
Cynthia Dyer-Bennet (cdb) Mon 2 Feb 04 08:11
> There is no particular road map on how to > prevent Alz, other than eating right, exercising the body and the > mind, and keeping stress to a minimum -- and even all of that may not > make much of a difference. My mom took care of herself all her life. Good diet, minimal alcohol consumption, regular exercise for her body, worked as a primary grade teacher in an experiemental public school open ed program and did crossword and acrostic puzzles for amusement (IOW: she gave her brain a workout regularly, too). Oh, and didn't take HRT. But there she is, goofy as all get-out now. So I tend to go with the "may not make much of a difference" idea, myself. > Cynthia: Whoah. I certainly didn't mean to suggest that 98% were > showing marked improvement. They probably weren't showing much of > anything in the early going. Ah. Yes, sorry. I think I blurred two different stages of that research together. The experiments were initally performed on mice, with astonishing results. Can you talk a bit about transgenics and Dale Schenk's work with knockout mice? Is he still exploring that avenue? Are there any new developments on that front?
David Shenk (davidshenk) Mon 2 Feb 04 09:05
Mice have been critical in Alz research, because there are so many obvious ethical restrictions on what you can do with live human brains. (Animal activists will, of course, argue that it's unethical to exploit mice bodies and brains, but so far that argument has not carried the day). Scientists need animals to study how plaques and tangles form, and what substances might inhibit their formation. The problem is that no animal besides humans get Alzheimer's. (A few get plaques or tangles, but none get both). So geneticists figured out a way to play with the genes and create "transgenic" mice who have plaques in their brain. Those mice have been critical in the development of the vaccine and other strategies to eliminate plaques. You asked about Dale Schenk (different name spelling from mine, no relation), who works for Elan Pharmaceuticals. That's the outfit that invented the vaccine. They're of course still pursuing that vaccine, and I'm sure other avenues as well. I haven't checked in with them in a while. But you can be sure of two things: 1. A lot of people are racing -- RACING -- to come up with the right treatment, for humanitarian reasons and because there are billions of dollars to be made. 2. When they break through, you'l hear about it.
Paulina Borsook (loris) Mon 2 Feb 04 10:16
ah, the 'women twice as likely to get dementia' factoid was a fact i gleaned from reading a current issue of psychology today, while in my physical therapist's waiting room. it was one of those roundup diffs on the real/observed diffs between men + women --- include everything from how much more likelt women were to get arthritic knees to how much more likely men were to get autism + schizophrenia, etc etc. i think it was an issue from this summer...anyway, the dementia stat really leaped out at me because it wasnt somethingt i'd kjown. but then, this could be a function of the fact that women tend to outlive men, so have, say, 7 more yrs in which to develop alz/dementia...
David Shenk (davidshenk) Mon 2 Feb 04 10:22
I'll have to hunt that down and see where they're getting that. It's true that a woman is slightly more likely to get Alz than a man her same age AND that women tend to live longer. So if you put those two together, that is pretty significant. But when one boils it down to a simple phrase like "twice as likely," the danger is that people think that women are much more at risk for the disease for any given age, and that men are basically off the hook.
Paulina Borsook (loris) Mon 2 Feb 04 11:02
totally admit i may have garbled/exagerated the stat. but it was significant enuf that it leapt out at me. if i were to guess, it was the aug 2003 iss of psych today. also, to continue to treat you as the snopes.com of alz --- had you heard that bypass surgery in folks over 80s in 40 percent of cases leads to irreversible mental decline into dementia? this wasone of many reasons i quietly raise some ah question to my evil mother when she was a candidate for such a few yrs back --- even then, she was considered too frail, for example, to have her carotids reamed out -- and lo and behold, that's exactly what happened. her dementia got precipitously worse afterwards --- whiuch makes an intuitive kind of sense, giving what an invasive shock to the system such surgery is. prob is, i dont remember where i read that stat when i was doing the research back 5 yrs ago --- and havent been able to come across it since..
David Shenk (davidshenk) Mon 2 Feb 04 11:12
I haven't heard that one, either. That also sounds very high to me. I'm pretty confident that there is no known association between surgery and Alz -- people ask me about that all the time. It does sound conceivable that there could be a connection to vascular dementia, but I haven't heard that -- and I think I would have if it really existed. But I can't be snopes on this one. I'm getting that you're not crazy about your mother.
Paulina Borsook (loris) Mon 2 Feb 04 11:38
nope, not crazy about my evil mother. but i still make sure she has the best and most considerate of care... yeah, i do feel sorta nuts about the surgery/vascular dementia thing, because it is NOT the sort of thing i would be inclined to make up...but it could have been in a study not well known; obviuously not the sort of thing vascular surgeons would like to focus on, etc etc also, there was an age issue here. it was only in folks in their -80s- where this effect was noted. not an issue, afaik for folks in their 50s + 60s, who constitute perhaps a larger pop of folks getting such interventions...
David Shenk (davidshenk) Mon 2 Feb 04 12:11
I just did a little digging and will email you two articles -- too long to post here I think. Both speak to the very real problems of post-bypass cognitive deficits, distinguishing between short and long-term deficits. Neither one seem to point to any definitive info on actual dementia setting in, which leads me to believe that there's very little data available on that.
Paulina Borsook (loris) Mon 2 Feb 04 12:48
well, it's a very small pop --- folks in their 80snhaving bypasses, and then being studied for cognitive malfunction.... issue with my mother is that it -exarcerbated- a relatively slow decline into dementia. again, that's a hard pop to find/study i.e. folks who have perhaps mci, have bypasses, are much worse 6-12- months later...the surgery sure didnt seem to help blood flow to the brain...anyway, this is probably wayn too off topic for folks who are more concerned with the tradtional and mysterious pathways to dementia...
Ted (nukem777) Mon 2 Feb 04 13:04
Hi David, I am a live-in caregiver for an 87 year old couple. The husband has Parkinson's and they are both showing signs of early stages of Alzheimer's. I can't tell you how much I appreciate all your efforts. I found your book very helpful and PBS rebroadcast The Forgetting last night - what a powerful presentation. The links from both PBS and your site are excellent. We should probably keep posting those as we go along. http:www.pbs.org/theforgetting and http://www.theforgetting.com Hope I got those right. I sense that your book has drawn you full-time into the Alzheimer's front. I can't think of anyone better and am glad we have you. Did you see any of this coming? And are you feeling a bit like the train is now pulling you along? Also, I can't help wondering about the greater ethical issue of outliving ourselves in terms of quality of life. Seems like we are caught in the middle of what science can give us as we live longer and the consequences of that as our bodies are unable, as yet, to handle it. Would you speak to that a bit?
David Shenk (davidshenk) Mon 2 Feb 04 14:44
Hi Ted. Thanks for the very kind and welcoming words. See this coming -- absolutely not. If someone had told me years ago that I would one day be jetting around the country giving lectures about Alzheimer's disease, showing excerpts of a film named after a book of mine, I'd have recommended a neuropsychologist for that person. Alz is not my full-time life. Part of my brain has moved on to my next book on something completely different (a cultural history of chess and chess's surprising influence on culture and ideas). But, yes indeed, it is a huge and important part of my life, and has made me a much better person I think. You touch on a central issue of our time, one which fascinated me as I was writing the book. Living longer is a natural human craving which has no chance of abating, but it is packed with unexpected consequences, paradoxes, and some just plain ugliness. Jonathan Swift wrote about this in Gulliver's Travels. He created an immortal race called the Struldbruggs in order to satirize the quest for immortality. His character Lemuel Gulliver is at first thrilled to find out about the Struldbruggs' immortality. He anticipates what they will be like: "Happy People who enjoy so many living Examples of antient Virtue, and have Masters ready to instruct them in the Wisdom of all former Ages!" The immortal elites, he reasons, will provide the best possible insurance against the repeating of past mistakes. With a living history as its guide, civilization will inevitably become smarter and stronger." But Gulliver has gotten it all wrong. After much laughter at his expense, he is told that immortality, far from being a blessing, is in fact the worse imaginable curse. The actual lives of the Struldbruggs fell into this pattern: "They commonly acted like Mortals till about Thirty Years old, after which by Degrees they grew melancholy and dejected....When they came to Fourscore Years, which is reckoned the Extremity of living in this Country, they had not only all the Follies and Infirmities of other old Men, but many more which rose from the dreadful Prospect of never dying. They were not only opinionative, peevish, covetous, moreose, vain, talkative; but uncapable of Friendship, and dead to all natural Affection, which never descended below their Grand-children....They have no Remembrance of any thing but what they leartned and observed in their Youth and middle Age, and even that is very imperfect....In talking they forget the common Appellation of Things, and the Names of Persons, even of those who are their nearest Friends and Relations. For the same Reason they never can amuse themselves with reading, because their Memory will not serve to carry them from the Beginning of a Sentence to the End." Swift himself was obsessed with senile dementia, and foretold his own case of it. It's an incredible story that I get to tell in some detail in my book. Today, we have a burgeoning immortality industry, gearing up to tweak our genes so that we may live an extra hundred or two hundred years or more. It would be laughable if it wasn't serious and even plausible. They'll be doing all this and more as the genetic revolution unfolds. But do we want it? My gut tells me that there's a wisdom built-into a billion years of evolution that we won't ever fully comprehend, and that tinkering with it is akin to tinkering with the atom. Let's ask the people of Hiroshima or Chernobyl if they think that is such a good idea. I may have jumped ahead of your question a bit. I think you were really aiming at more conventional means of helping us live longer, and of course there it gets even more difficult to parse the ethics. If I told you at age 75 that you had 2 years left, but I could extend that by 15 years with a bypass -- BUT that the final 10 of those years would be marked by Alz and would decimate you and your family's emotional and financial lives -- what would do you? Something close to that scenario is playing out thousands of times every year now, except we can't tell for sure which ones of us will get Alz and which won't. It'll really get interesting when we have better tests and can predict our final years better.
Ted (nukem777) Mon 2 Feb 04 15:11
You were right on target. Thanks. Ray Kurtzweil speaks about this quite eloquently in The Age of Spiritual Machines. I think our generation is in for a not-so-pleasant future while we make these transitions.
some kind of ethereal transitive tense thing (katecat) Mon 2 Feb 04 15:30
The question you ask in your last paragraph is a fascinating one-- fascinating for us as a species I guess I mean, since as individuals we don't get to make that choice (and it would probably not be a hard one for most of us).
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