Inkwell: Authors and Artists

    


We asked our next guest, author David Shenk, to tell us how he'd like to be
introduced. He replied:

"I'm home again. A dozen years after the fact, I'm very excited to return to
my first Internet base camp. I joined The WELL in 1991 (connecting at 9600
baud, I think), and was awarded the Internet address
"well!dshenk@lllwinken.llnl.gov." I think I'd like to put that one on a
tshirt someday.

I later strayed but remained semi-connected to WELL culture through several
close friends, most notably the great Digaman (Steve Silberman, as if I have
to spell out his name to you). My first book was co-written with Steve.

Since then I've published three other books (no one but myself to blame for
those), written for a number of magazines I admire, and contributed to NPR
now and again.  More on my writing can be found at my vanity homepage,
www.davidshenk.com. I live in Brooklyn with my best-friend/wife Alex and two
sensational kids if you don't mind me saying."

David is the author of "The Forgetting -- Alzheimer's: Portrait of an
Epidemic," a bestseller that explores the physical and psychic toll this dis-
ease takes on its victims and their families, and delves into science's
search for a cure.

Cynthia Dyer-Bennet is leading the conversation. Cynthia is a former educa-
tion reporter who is now in her sixth year as Conference Host Manager for The
WELL. Her interest in this book is personal. For the past 11 years, Cynthia
has been helping care for her mother's increasing needs as Alzheimer's Dis-
ease relentlessly transforms the brain of a once lively, intelligent woman
into a useless tangle of ruined neurons.
  

    
Thanks for the intro, (tnf). And welcome, David. Despite the years I've
already invested in learning about this disease, your book has given me so
much more information to digest. Thank you so much for writing it!

Before we delve too deeply into the details, I'd like to ask you to provide
all of us with some of the basic information about Alzheimer's.

Can you give us a general description of the physiology of Alzheimer's?
What causes a person to "lose his mind" to this disease?
  

    
Sure thing. The biology of this disease is fascinating and terrifying.
It's also very complex, but I'll give you a general outline of what
happens. 

Alzheimer's is caused by two aberrant, malicious protein fragments
known as "plaques" and "tangles." These are the two hallmarks of the
disease first noticed by Dr. Alois Alzheimer in 1906. How they form and
where they come from is complicated, but we do know that they always
begin to form in the exact same part of the brain in every single
Alzheimer's patient: the Hippocampus, a seahorse-shaped nodule of the
brain located inward from the ear. The Hippocampus is crucial to the
formation of new memories.

The plaques and tangles themselves are not partial to destroying
memories. They'll destroy anything they can. Since they're in the
brain, that means that they're destroying nerve cells (neurons) and
neural pathways (synapses). And because the plaques and tangles first
form in the Hippocampus and destroy neurons there, short-term memory is
almost always the first ability to be compromised by the disease. 

It's not that people are forgetting things, per se, but that they're
not forming any new memories in the first place. New experiences come
and go without any retention. (Older memories are still intact for the
time being).

After a few months or a few years (the progression can be very slow),
the plaques and tangles start spreading into different parts of the
brain. This they also do in a predictable fashion. In very crude terms,
their second destination is the front of brain, where we do all of our
complex thinking -- sorting out logic, considering ideas, making lists
of things we want to be doing in the immediate future, and so on.

So we call the middle stages of the disease "confusional," because
people get very confused. They lose all the attributes that we
associate with a thinking person. They don't make sense in their
speaking, can't understand what others are saying, get confused about
time, lose a grasp on when older memories took place, and so on.

In the late stages of the disease, the plaques and tangles move toward
the back of the brain and start to destroy the those areas that
control muscular movement and vital functions like breathing and
swallowing. So in the end, the disease is fatal. Alzheimer's will kill
you, unless you die of something else in the meantime.
  

    
> After a few months or a few years (the progression can be very slow)

Absolutely! I've seen Alzheimer's sufferers go from talkative and only
slightly confused to totally non-verbal and lost inside themselves in 
less than a year. In my mother's case, her short term memory problems 
began eleven years ago, and though she's quite confused now, she's
still verbal and able to relate (though often oddly) to other people.

Your answer raises so many more questions, David. You've touched on the 
stages of the disease, for example, and I'd like to delve deeper into that 
shortly. We'll also talk lots more about the science of plaques and 
tangles over the next two weeks.

Before we get there, though, I'm thinking of how at sea I felt when it 
first became apparent to me that my mother was afflicted with this disease. 
I flailed around, not knowing what kind of help she needed nor how to get 
it. Can you suggest some resources people who are facing this situation -- 
either as caregivers or as early Alzheimer's sufferers -- could turn to?
  

    
The feeling immediately after diagnosis can be overwhelming. I'm here
to assure people that there are some terrific resources available if
people look hard enough. 

First, always, is the Alzheimer's Association. They have local
chapters everywhere. You can go to  www.alz.org or phone 800-272-3900.
They can steer you to local support groups, doctors, and other
services. They can also recommend literature.

For people comfortable with email, I strongly recommend an email
newsletter called Alzheimer List. Its roughly 1000
subscriber-contributors include caregivers, social workers, doctors,
researchers and patients themselves. Here you can get information on
specific drugs, advice on wandering and sleeping problems and a
full-range of emotional support from people who have already been
through what you are going through now. Find out more about it at:
http://www.adrc.wustl.edu/alzheimer/newbie-new.html

Beyond that I would recommend checking out two websites that I'm
associated with. The original website for the book --
www.theforgetting.com -- has some excellent resource material, as does
the new website companion to the film, at www.pbs.org/theforgetting.
  

    
Those are some great recommendations. The Alzheimer's Association has been a
major help to me, both as a practical resource and as a place for gentle
advice. And I can't say enough good things about support groups. This is
such a long, hard process; it's so important to have other people to talk to
-- be it face-to-face or virtual -- who are going through the same thing.

I've already explained that my interest in this subject is personal, both
because my mom has Alzheimer's and I'm a likely candidate for it myself.
What got you interested in this, David? What made you want to write this
book?
  

    
Such a fantastic book, David. Thank you so much for all your efforts.
Would you share some of the numbers with us, in respect to what's
coming our way in regard to this disease? I had no idea how
overwhelming Alzheimer's is becoming.
  

    
Hi there. I've just started taking a semester long course in Alzheimer's,
taught by William Jagust at the UC Berkeley School of Public Health. I'm in
the doctoral program there, and am working on a minor concentration in Aging.

There's also a strong run of Alzheimer's in my dad's family, he and my
sisters are at risk, and it's good to be as prepared as one can be.
  

    
I meant to say, "he and my sisters and I" of course. Hmmm....

We've had one meeting of the class so far, and "The Forgetting" was
mentioned by several of the students and (I think) the prof. The course
readings are classic and new journal articles, mostly, and cover medical
research and clinical practice. I'm also interested in health policy and
aging in general, but the class won't cover much about policy.
  

    
Hi. I've almost finished reading your excellent and informative book. I'll
have lots more to say and ask (my mother is in the early stages of
Alzheimer's, and her father had it and lived with us until he became
violent); right now I just wantto say how moved I was by the story of the
man trying to think how he could keep his human dignity, as the disease
progressed; and how he decided that compassion would be wit him until near
the end.
  

    
>after you get diagnosed

Which happens how? Is it symptomatic ("well, you act like you have it,
so you must have it") or is there some sort of test? And at what point
does one decide to see whether one has it and isn't just having a
Senior Moment?
  

    
Just checking in as a very interested (although so far disinterested) party.
  

    
Hello all -- and sorry for the delay in responding. I'm finishing up a
48-hour trip to Salt Lake City -- an Alz conference. I've got to catch
a plane soon, so I'll be brief now but starting later tonight I'll be
much better about responding quickly. Here are some quick takes on the
questions above:

Number counts for Alz patients are all pure guesswork, but as best we
can tell, the numbers have risen from 500,000 Americans with the
disease 20 years ago to about 5 million now. The real explosion,
though, will happen over the next 25 years, as the baby boomers get
into the risk prone years. (The first baby boomer turns 65 in 2011). So
that's the race against time that's going on in the research world.
It's expected that by 2050, 14 million Americans or more will have the
disease, and the annual cost could be 400 billion dollars.

On genetics: just because you know of one or more cases of Alzheimer's
in your family doesn't necessarily mean you have a much better chance
of getting the disease. There are genetic components to the disease,
but the most important risk factor by far is age. 1% of 65 year olds
have Alz. 10% of 75 year olds. 20% of 85 year olds. Every year we age
increases our risk. All the studies you read about estrogen or
testosterone or bumping your head or this or that -- all that stuff is
more relevant to scientists than it is to us. I don't have any cases of
Alz in my family history (as far as I know), but I consider myself
just as much at risk as anyone else out there.

There is no definitive test available right now to disgnose
Alzheimer's -- no blood test or PET scan or anything like that. But
doctors who know what they're doing can give you a very accurate
diagnosis using a battery of memory tests. Researchers in Pittsburgh
have just invented a compound that enables them to see plaques inside
living brains (using a special PET scan), but this won't be available
as a diagnostic tool for quite some time. It WILL be almost immediately
useful as a tool for advancing the study of potential anti-Alz drugs.

Difference between normal forgetting and Alz: We all forget, and we're
all frustrated with our memories. In fact, I think that our
increasingly complex and distraction-laden world increases this
frustration significantly (See my book DATA SMOG). Memory also
naturally becomes less sharp as we age. You don't need to worry if you
occasionally can't remember a name or a word (this happens to me all
the time, at age 37), or misplace your glasses or car keys. That's
distraction. More worrisome is when you don't realize you're
forgetting. Your wife looks at you when you ask her something and says,
"You just asked me that 5 minutes ago," but you have no recollection.
Or a friend calls up and says "where are you -- we were supposed to
meet," but you have no memory of forming that plan. That's when you
want to get checked out, because those situations show that you may
have a problem of not forming new memories.

More later. Keep those questions coming.
  

    
david, i thot i had heard the statistic that -50 percent- of
folks over the age of 85 have dementia. now perhaps
that is dementia in all its many lovely varied forms...
including folks like my evil mother, age 87, who has
a mixed dementia pattern (alz + multiple infarc), which
i think is pretty common... dont want to get you off
topic, but how misleading is it to be talking about
'alz' (and its terrors and remediations) vs 'dementia'
overall? certainly with my mother, she is -on- the
current alz medications, so her treatment isnt any
different...
  

    
I gather from David's book that medical science has adjusted it's thinking
on just how common Alzheimer's is as compared to other types of dementia.
I'll leave it to him to offer more details, though, since I wouldn't want to
put words in his mouth.


> I'm finishing up a  48-hour trip to Salt Lake City -- an Alz conference
> I've got to catch a plane soon ...

Hello and g'bye. You must be exhausted! If this isn't too much of a
sidetrack, what did you do at the conference? And were there any new
encouraging developments in Alzheimer's research announced?
  

    
Hi Paulina,

You're right that with some of my stats I'm lumping all of the
dementias together and referring to them as Alz, when it would be more
accurate to say "Alzheimer's and other types of senile dementia." This
subject is so incredibly complex that my job of writing about it and
explaining it becomes a series of simplifications in order to help
people understand the basics. As you know, this is one of the hazards
of non-fiction writing, particularly of writing about science and
technology for a general audience. 

Alzheimer's accounts for the majority of cases of senile dementia.
Multi-infarct dementia, which is also known as vascular dementia or
"mini-strokes" is the next most common, and as you've illustrated,
there are connections between the two (not entirely understood), and
it's common for patients to have both. (It's also fairly common, by the
way, for people with Parkinson's to develop Alzheimer's, and
vice-versa). 

After Alz and Multi-infarct, there are a few other (much rarer) causes
of senile dementia. My book is ostensibly about Alzheimer's, but in
fact most of what I write about -- the ancient history, the mechanisms
of the brain, the challenges of caregiving, even much about the
progression of the disease -- applies quite well to multi-infarct
patients and to Pick's patients and all the others.

If you want we can delve deeper into either A) the pitfalls of
simplification or B) the details of the different dementias. (For
example, when you really get into the nitty-gritty, there are probably
many different kinds of Alzheimer's disease -- but the differences are
really only relevant to scientists at the moment). There are inherent
problems when we tread into general discussions of these issues, but
I've been heartened to discover that many of the scientists I respect
in this field have read my book and heard me give presentations and
have given me the thumbs-up on how I navigate the complex truths. So
that gives me some comfort as I simplify and simplify and simplify all
day long.
  

    
I should also add quickly (and we can later talk about this) that the
50% study is itself problematic. No other study has come up with that
figure. But it does seem evident from all the studies that every year
we get older increases our risk of succumbing to one of more of the
dementias.
  

    
Dave,    I recently attended a conference on Alzheimer's disease
(hosted by Pfizer) and was told that the special PET scan that you
spoke of earlier may only be a couple of years away. The problem is
that it will be very expensive and getting payment will be difficult.
Also, since people only begin to become aware of Alzheimer's in a loved
one when it's fairly advanced (late stage 3 or stage 4 for those who
keep up with those things) a routine PET scan at, say age 60 (much the
same as a colonoscopy is done at 50) would really be helpful in
diagnosing the disease before there is too much progression. In
addition some researchers were touting the effectiveness of new
medications in slowing the progression to the disease to an almost
imperceptible crawl (Pfizer, remember?). Consequently, with early
detection and intervention it may be possible to really control this
disease. I know that overmedication is a serious problem for the
elderly so I hesitate to espouse maintanence medication to treat
Alzheimer's but my uncle has it, my grandmother died of it and I've
seen enough Alzheimer's patients to know how brutal the disease can be.
Any thoughts?
  

    
You're bearing down on some of the really good questions, Ron. There's
a lot to respond to here. First, what you've apparently been told
about the current drugs slowing the disease down is not true -- at
least as far as we know. The current crop of drugs known as
cholinesterase inhibitors (they include Pfizer's drug Aricept) really
only help alleviate some of the symptoms of the disease. That is, it
strengthens synaptic activitity in the brain to help make up for some
of the destruction going on. But the destruction does continue to
happen. 

The drug companies love to think that these drugs slow the disease.
They like to kind of suggest that maybe they do, but it's wishful
thinking so far -- a lot like Bush's WMD's in Iraq. They really haven't
show that and it's very very clear from many people who have taken
these drugs that they help for a little while and then basically wear
off. These patients then find themselves in the middle stages of the
disease and fade away further from there.

That point does not negate any of the other points you make. It would
be fantastic to have a gold-standard diagnostic tool like a PET scan to
tell us that Alzheimer's is creeping in at the very earliest stages.
Combined with the next generation of drugs that will hopefully be here
over the next 5-10 years, drugs that will slow the disease down or even
stop it completely, we could radically curtail the devastation of this
disease. But we're just not there.

I know for a fact, having just corresponded with the lead authority in
Pittsburgh where they've invented this new PET-scan compound, that
there are no current plans to quickly make it available as a diagnostic
tool. I think it will happen, but it's not around the corner. We can
get into the reasons for that if you want. 

More immediately, the compound will be used in conjunction with
experimental drug studies to measure their effectiveness. If clearing
away the plaques can stop the disease, this compound is a critical part
of those experiments that will get us there.

Until we have a gold-standard diagnosis, we'll have to rely on the
battery of memory tests that we have, in conjunction with tests that
rule out other diseases. This sounds crude, but it's actually extremely
reliable when performed correctly. 

One other slight correction to what you said above. It is true that a
lot of people are not getting diagnosed until the late-early or
early-middle stages of the disease. But with all this awareness of the
disease, more and more people are getting diagnosed in the very
earliest stages. In fact, many people are getting diagnosed with a
pre-Alzheimer's condition called Mild Cognitive Impairment -- MCI. They
don't have enough signs to really call it Alz yet, but a huge
percentage of them do go on to develop full-blown Alz.
  

    

   (Reminder to those reading off-Well: you can participate by
   sending e-mail to us at inkwell-hosts@well.com )
  

    
David, you discussed plaques and tangles briefly. Can you explain in more
detail how they do their damage?
  

    

> I know for a fact, having just corresponded with the lead authority in Pit-
> tsburgh where they've invented this new PET-scan compound, that there are
> no current plans to quickly make it available as a diagnostic tool. I think
> it will happen, but it's not around the corner. We can get into the reasons
> for that if you want.

I would be interested in knowing more about this.

I would also like to know more about the drugs that are available now, e.g.
Mementine, which was recently cleared for sale in the States.  A family of my
accquaintance was getting it from Canada before that.

What drugs are used for Alz patients, and how do they work?
  

    
Let me try to tackle Cynthia's and David's questions in concert.

The plaques and tangles together destroy neurons and the synapses that
connect them. Plaques do this from outside the nerve cells. Picture
them literally blocking the path of synapses between neurons. Tangles
are black stringy things that form inside neurons and basically
strangle them from the inside. 

There are two classes of drugs currently available for Alz patients,
neither one of which actually do anything about the placques or
tangles. Both instead basically try to make up for some of of the
destruction caused in their wake. 

The first class is the cholinesterase inhibitors -- Aricept, Exelon
and Reminyl. They're generally considered useful for early stages,
lasting a few years at best. They can help patients be a little sharper
and possibly less frustrated and calmer for a while.

The second class only includes one drug so far -- Memantine, or
Namenda as it will be called in its branded form. It's an
N-methyl-D-aspartate (NMDA) antagonists, which blocks the amino acid
glutamate, and, again, helps gin up the synaptic process to its maximum
efficiency as so many cells and synapses are being destroyed. 

There's of course more detail behind that, but we're almost at the
limit of my knowledge, and to dig further into how these drugs work
would require quite a bit of background and brain knowledge. 
  

    

Thank you, David.

BTW, a friend recently passed along the 9/10/2001 issue of The New Yorker,
which contained a very fine article by Jonathan Franzen titled "My Father's
Brain."  Franzen wrote touchingly of his father's decline, and also
referenced the book we're discussing here.  I don't thin it is available
online, but if you can find the magazine, the piece is well worth reading.
  

    
It is a beautiful piece, David. He's a terrific writer. I have mixed
feelings about it, though, because he uses an awful lot of info and
understanding straight from my book in the first several pages before
he begins to actually acknowledge the book. It would have been fine if
they had identified it upfront as a book review, which was how it was
originally assigned and how a lot of Malcom Gladwell's pieces appear.
But they ended up listing it as an essay with no upfront
acknowledgement of what had started the ball rolling. My publisher was
livid, as you can imagine.
  

    
Interestiing that TNY reframed the piece without consultation that way.  But
still, it must have been great publicity for the book.