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Memory Enhancement (transcript)
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Major funding for Second Opinion is provided by the Blue Cross and Blue Shield Association; an association of independent locally owned and community based Blue Cross/Blue Shield plans committed to better knowledge for healthier lives.


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(Dr. Peter Salgo) 
Welcome to Second Opinion where each week we solve a real medical mystery.  When we close this file in a half an hour from now you'll not only know the outcome of this week's case, you'll be better able to take charge of your own health care.  I'm your host, Dr. Peter Salgo and you've already met our special guests who are joining our cast of regulars, primary care physician, Dr. Lisa Harris and Glenn McGee.  Now, no one on the team knows this case except me.  I've got it in the chart, so let's get right to work.  We're going to talk about Ellen today.  We meet Ellen for the first time in her primary care physician's office.  Ellen is fifty-three years old, she's an engineer.  The chart notes that she's anxious, visibly distraught.  These are direct quotes. She says she "can't take it anymore."  She's worried that she's losing her mind and that she might be having early signs of Alzheimer's disease.  Now, Lisa, if you were her primary care physician, if you'd play that for a moment, how many times have you heard this before?

(Dr. Lisa Harris)  
It sounds like yesterday in my office, the majority of things that present into your office.

(Peter) 
What do patients tell you?

(Lisa)  
Exactly that.  I can't take "it" anymore and you usually have to spend quite a bit of time trying to figure out what "it" really is and she's helped you out a little bit by telling you that she's worried that she has early Alzheimer's but you really need to get some more information about why does she think that.  What else is going on in her life that's causing her to feel so distraught and anxious?

(Peter) 
Before we begin to drill down on this let me open this to everybody here.  Are her complaints unusual?  Lisa says they're not, but baby boomers are coming of age and we're going to hear about this.

(Cathryn Jakobsen Ramin)  
They're definitely not unusual.  These are very, very common complaints.  Basically, most people in mid-life talk about problems with forgetfulness.  The fact that she appears so anxious and distraught could lead to some questions about other psychological issues, but it could just be a reflection of problems in terms of career and forgetfulness.

(Mark Mapstone)  
I would have to say in my practice that this is the modle patient.

(Peter) 
What is a modle patient?

(Mark)  
The patient that I see most frequently is a woman in her mid to late fifties who's complaining of memory loss, although we haven't heard that from this patient yet, but we've at least heard that she's concerned about Alzheimer's, so this is very common in my practice on memory disorders.

(Peter) 
How many people in America have Alzheimer's right now?  Is it four and a half million or something like that?

(Cathryn)  
Five million.

(Dr. Peter Salgo) 
A huge number and as you grow older, of course, that percentage goes up, right?

(Aaron Nelson)  
Age is the number one risk factor for Alzheimer's disease.

(Lisa)  
You mentioned the baby boomers.  The baby boomers multi-task more than any other generation before and they super multi-task their kids and their grandkids, so there are other things that I really want to know about before I jump to you have memory loss.

(Peter) 
Let me tell you about Ellen.  Lately she says she's been forgetting things.  She blanks on names of people that she works with.  I'm reading this right here.  Sometimes she can't find the word that she's searching for.  She says her mind feels like it's cluttered and last month she lost her car in the parking lot of a large shopping center and felt panicked, then when she found her car, drove it home, she realized that she left her purse way back at the shopping center.  Now, Aaron.

(Aaron)   
I've done some research.  You're naming three of the top ten complaints that patients come with.  A word finding problem - it's typically a low frequency more complicated word, names, losing the car.  These are very common complaints that usually end up pretending not much in terms of the real clinical diagnosis or problem.  A couple things about this case that strike me - here's a patient who herself is presenting with a complaint.  Statistically speaking the chances of her actually ending up with a diagnosis of Alzheimer's disease are much smaller.

(Cathryn)  
No, that's not really accurate.  You're operating from a very old fashioned point of view on this -

(Aaron)   
No, I don't think so.

(Cathryn)  
Which is until the patient shows up and can't use a key to get in the house there's nothing wrong.

(Aaron)   
No.  No.  No.  That's not what I said.  Statistically speaking the number of patients who actually present with memory complaints compared to those who are referred by a spouse, a loved one and so forth -

(Cathryn)  
It's because it's late in the game.

(Aaron)   
No, it's not, it's because the insight that a person needs to mount in order to have that self critical, self observation capacity, typically begins to erode along with the memory.  There are normal age related changes in memory which are distressing, but are not necessarily part of the disease process per se.

(AMY ARNSTEN)  
Well, what I'm keying in on Ellen is that the things she's complaining about now are very common and they're the territory of a part of the brain called the prefrontal cortex which we know from monkeys who also have these same cognitive profiles starting in middle age and one of the things that's hardest for them is multi-tasking and set shifting.  There is a true biological basis and work in monkeys has been marvelous in elucidating what's going on because they don't get Alzheimer's disease.

(Cathryn)  
There are physiological changes that occur in terms of processing speed as we move from our thirties into our forties and into our early fifties, but what has happened particularly to the boomer generation and also to Gen X, the eldest of which is now forty-eight years old, as processing speed declines the demands on our lives and on cognitive abilities escalate.

(Glenn)  
Those folks, they are thinking about a world in which people have six or seven careers.  They retire into another one.  It is very difficult and quite understandable to imagine that when they're faced with a computer they don't know about, a job they don't understand, that they'd say good Lord, what are the words for this?  These people talk so fast, they work in a different way and whether they're right or wrong their complaint makes sense.  I think the fight is about whether their complaint is properly medical or not.

(Aaron)   
Exactly.

(Glenn McGee)  
And that's expanding the territory of medicine.

(Aaron Nelson)   
That's right.  When a patient comes to me and complains about their memory I accept that one hundred percent.  That does not mean that that memory complaint will lead to a diagnosis of Alzheimer's disease or some other dementia.  I do take that seriously.  I also believe that there are therapeutic and treatment and lifestyle options which need to be brought to bear even in non-disease age related memory problems.

(Peter) 
Cathryn, you came to all of this because you were having this problem.

(Cathryn Jakobsen Ramin)  
That's right.  I'm the guinea pig here.

(Peter) 
You are our patient here.

(Cathryn)  
I am.

(Peter) 
You have an insight into what this was like.

(Cathryn)  
I took it a little further than most people do in that as an investigative journalist I thought that this was going to have a very serious impact on my career if I could not get it in hand and in my case it got going in my early forties.  I was somewhat concerned that these could be early signs of Alzheimer's disease and by mid-forties I decided that it was now evident that it was happening all around me.  Everywhere I went people were talking about losing their minds, losing their trains of thought and a whole lot of other things so I decided that I would write a book and I would seek ten interventions.  At least that's how it turned out, that there were ten looking for solutions to a problem.  There's a point that I want to make here, which is, yes, this is normal.  No, it is not acceptable because of the lives we're leading.

(Mark)  
I would add that with regard to Ellen's case there are two key points that I think should direct us here.  One, she describes her mind as cluttered.  Two, she says she gets panicked when she has these memory lapses.  Those don't sound like Alzheimer's-like changes.

(Peter) 
I'll tell you what she shares with her doctor.  She says that her grandmother developed Alzheimer's in her seventies and of course she's worried that she's going to get it because her grandmother had it.  That her mother was never any good at remembering her, Ellen's friends' names and she's worried that she's going to end up just like them.  Given this history, given what she's told her doctor in addition to this history does Ellen have a fair chance of winding up like this?  Is this a real concern for her?

(Aaron)   
A positive family history does increase the risk for an individual above someone without the positive family history, but the vast majority of people who eventually come to the diagnosis of Alzheimer's disease don't have a positive family history or at least not in a documented one.

(Dr. Peter Salgo) 
She's fifty-three years old.  What would be normal memory loss for her and what would be abnormal?

(Aaron)   
The kinds of things we talked about before.  Forgetting a word, forgetting a name, especially somebody who's kind of an acquaintance, not a close family member.  They're problematic, they're annoying, but they're very common in normal aging.  What would be more worrisome would be the patients who forgets a name of a grandchild.  Who forgets how to get to such and such a store they've been driving to for the last twenty years.  Who forgets what they had for dinner last night.

(Peter) 
We're using a word we haven't defined.  What's memory?

(Amy)  
There are many types of memory and many brain systems that sub-serve them and they are differently affected with normal aging in Alzheimer's disease and in Parkinson's disease.

(Peter) 
So what's short term memory?  What's long term memory?  You hear about this all the time.  Oh, my short term memory is shot, but I remember the World Series in 1960.

(Mark)  
I think we can start off even higher than that.  I think a very simple definition of memory is the acquisition, retention and retrieval of information and if we think of about it that way we can then start to parse it into its different forms.  Short term memory is the ability to immediately register and hold information on line and be able to spit it back relatively in its same form.

(Peter) 
But then you have to incorporate some of that short term memory into a long term memory otherwise you lose it.

(Mark)  
In general short term memory is necessary for long term memory.

(Peter) 
Let me give you a little bit more information about Ellen.  She's got a normal blood pressure, a normal cholesterol.  Her two teenagers keep her pretty active.  She's experiencing symptoms of menopause.

(Lisa)  
That would do it for you.

(Dr. Peter Salgo) 
That would do it for you you said.

(Lisa)  
Definitely.

(Peter) 
Poor sleep. The only medication that she's taking is Tums and she's taking it because she wants the calcium.  Do you say that her hormonal changes are what's causing all of this and do hormonal changes cause you to forget?

(Mark Mapstone)  
We did a small study looking at perimenopausal memory complaints and so we wanted to look at what we are concerned about which is retentive memory, so you can think of encoding, retention and retrieval and it sounds when you listen to these women that they're describing retrieval based problems or possibly encoding problems, but they don't really forget information; they're having trouble retrieving it.  This sounds a lot like Ellen's problem and what I see a lot in clinic.  It sounds like an attentionally based problem. This is not retentive.  She's not forgetting information.  She's having trouble encoding it and then possibly retrieving it when she does get it in.

(Peter) 
Could she simply be depressed and does depression have an affect on your memory?

(Lisa) 
We'd really need to sit down and do an assessment of what her daily lifestyle is like and what things that we can do to try to simplify her life.  You can do a depression inventory, you can do an MMSE, a mini mental status examination.  So those are simple things that I would do first and foremost.

(Glenn)  
We've got a history in our society on the one hand of thinking about women and depression in ways that don't serve women's interests in a lot of ways and menopause is just one of those things that everybody looks at and says oh dear and at the same time we don't spend anything like enough money on research to make these distinctions.

(Peter) 
Before we go any further we have been discussing Ellen and most of our discussion has focused on women whether it's menopause, hormones, what have you.  If this can all explain memory problems in women what excuse do men have?

(Lisa) 
They don't have estrogen.

(Aaron)   
Men actually do go through hormonal changes as they age as well.  We know that reduced levels of testosterone are going to reduce things like drive.  They definitely affect prefrontal cortex, connections, motivation.  The kinds of things that you need in order to process information rapidly and maintain attention and so forth.

(Peter) 
I want to pause for just a minute because we have to sum up where we are.  We've been covering a lot of ground here.  Forgetfulness is a part of life.  While normal aging may entail some neurologic changes that affect memory, not every memory problem is a symptom of dementia.  We really haven't talked a lot about dementia; we've been talking about memory, although that's what Ellen is worried about, so let me tell you a little bit more about Ellen.  Her primary care physician says enough.  This is beginning to get beyond my area of expertise and sends her to a neuropsychologist for further testing. Lisa, does that sound reasonable to you?

(Dr. Lisa Harris)  
There are some things that I would have done before that that we don't have in the chart.  I'd really like to have some other information, but -

(Cathryn)  
You definitely want to have some thyroid levels.

(Lisa)  
I would have given her a trial of HRT if she's menopausal and talked about getting better sleep patterns, so it would have been a little bit more of a workup.  I would have tried some of these interventions and then referred her to -

(Peter) 
In the real world Ellen does get referred and she goes to a neuropsychologist.  Aaron, Mark, you're the experts here.  Comes to you, what are you going to do? Mark, you want to start?

(Mark)   
Clearly you have to do a detailed clinical history.  I get most of my information with patients out of what they tell me.  During that time I'm going to be formulating hypotheses and I will then select tests, standardized neuropsychological or cognitive tests, that I will use to start investigating those hypotheses.

(Dr. Peter Salgo) 
Aaron, what are you going to do?

(Aaron)   
My experience has been that if you listen carefully the history will tell you what the patient's diagnosis is.

(Peter) 
But Mark thought that he'd do some lab tests.  How are these lab tests, whatever they may be, and you could tell me what you'd like to order - how are they going to help you to sort out what Ellen wants you to sort out - Alzheimer's versus normal aging and forgetfulness.

(Aaron)   
We're looking at Ellen's performance relative to same age peers, relative to people with similar backgrounds and also relative to what you know about her own baseline, her own estimated baseline.  This is a woman with probably of at least above average intelligence.  She's an engineer.  There are certain expectations that creates in terms of how she should be able to do generally speaking.

(Peter) 
So let me whip some tests out at you.

(Aaron Nelson)   
Sure.

(Peter) 
Tell me if you like them or not.  Going to do an EEG or a brain wave analysis.

(Aaron)   
That could come into play down the road if we suspect that there's some brain electrical issue.

(Peter) 
What about MRI?

(Aaron)   
That would not be the first thing we would push.  I think that imaging may or may not come into play here depending on what we find.  If her neuropsychological exam is normal it ends there.  We now have a baseline.  We can follow Ellen over the years to see how she does.

(Peter) 
Anybody recommending or going to recommend a lumbar puncture or spinal tap?

(Lisa)  
Unless you see a change in the back of the eye that would indicate an increased pressure in the brain and you're looking for something called normal pressure hydrocephalus then there really wouldn't be an indication to do a lumbar puncture unless she had something else really dramatic.

(Dr. Peter Salgo) 
The reason I'm asking this is that Ellen's been on the Web and these are in her mind.  Let me ask you some very quick questions.  Ellen came with this complaint.  She went through a battery of tests.  Is the panel suggesting that everybody at Ellen's age needs a battery of tests to tell you that you're beginning to have normal forgetfulness.

(Aaron)  
Of course not and I think if you're looking for ways to spend the health care dollar it's not getting neuropsychological baselines for every person on the planet.

(Peter) 
Ellen had a full battery of tests.  She had psychometric; she had some genetic testing as well because she wanted it.  Her doctor tells Ellen I've got good news.  You have no sign of Alzheimer's.  You have no IQ loss.  Go home.  You're normal.  What do you think now?  Is Ellen happy?

(Lisa)  
No.  Her main concern is I can't take this anymore and as her primary care physician that's the complaint or the problem that I need to address.  The first thing we're going to work on is her sleep, so I would put her on HRT, on hormone replacement therapy, and we would go through sleep retraining.  That's a hard thing for patients to understand.

(Glenn)  
I think at a certain point in this process we begin to slip into a discussion that's less about what you might call treatment and more about what you might call enhancement.  She wants to be enhanced.  Can we do that?

(Aaron)   
And this refers to improving memory above normal.  If you're talking about restoring something or tuning something up to its optimal level of normalcy that's fine, but what about the patient that comes to you and says doc, I want to be able to have a super memory?  The analogy here is the athlete.

(Amy)  
You know what, you can't do that.  That's where the ethical problems come is people think they can come in as Homer Simpson and leave as Einstein.

(Peter) 
Before we get to enhancement let me go through what's available this second and then we're going to push forward.  She's read about vitamins, herbs.  She asks about special exercises.  Any of this offer anything?

(Lisa)  
In addition to working with her on how can we distress your life.  What are the things that are absolutely urgent and important for you to do on a day-to-day basis or things that can be pushed out to the side.

(Cathryn)  
I would want to know how much exercise she's getting.

(Peter) 
I'll tell you what's in the chart.

(Glenn)  
You're asking a question about whether she should go to a doctor.  She said yes and you're helping her with problems, but once you figure out how to solve what you can correctly describe as problems that were treated in a normal way - fix her sleep.  We deal with hormonal replacement therapy if necessary.  Now what?  She still can't remember.

(Cathryn)  
You can go a heck of a long way before you start giving people cognitively enhancing drugs and you should.  You should take every one of those steps - exercise, diet, supplements.

(Peter) 
Give me a list of things that work whether it's exercise - anything you'd like.  What if someone is complaining of memory problems can you tell this person to do that clearly works?

(Dr. Lisa Harris)  
Exercise.

(Peter) 
That's one.

(Lisa)  
Sleep.  Destress, declutter, simplify.  Follow up regularly with your doctor, multi-vitamin.  Menopause you certainly need either botanical or prescription hormone replacement therapy.

(Cathryn Jakobsen Ramin)  
And that is a very controversial stance that I happen to back you up on, but very controversial.

(Lisa)  
You can't say I can't do this and then just throw up your hands and say I'm not going to.  It's just like a diabetic or a heart disease patient or anything else.  You have to do this and my job is to show you how do you actually do it?

(Dr. Peter Salgo) 
I could tell you that Ellen asked whether all of these lifestyle changes would work and she was told by her doctor yes, they would.  Then she said typical baby boomer engineer, frantic, busy, I don't have time for any of that stuff.  I want a pill.  I want to fix my memory with a pill oh you who've done the research.  Where's the pill?

(Amy)  
We, I don't think have an optimal pill right now. One of the things that's a problem is different parts of the brain age differently.  What the prefrontal cortex needs is actually the exact opposite of what the hippocampus and these other memory systems involved with retention need and so we have to be very intelligent about this and design drugs that help correct one part without hurting the other.

(Peter) 
She's read that there are people out there taking Adderall, a drug for attention deficit disorder, and other people taking Provigil.

(Amy Arnsten)  
The data suggests that the stimulants like Adderall actually become less effective as we get older and it's because of how they work.  They need a somewhat healthy young system to kick in order to have their effects because they act indirectly and so we have to work on things that get at what's really changing in the aging brain and see especially things like bringing back in those stress pathways so that we can think more clearly and so we don't cause the erosion of the spine.

(Peter) 
Tell me what's on the horizon pharmacologically because Ellen wants the magic pill.  Don't we all?  What's out there?

(Amy)  
I would say there's still no pill substitutes for exercise that gives you oxygen.  Sleep that restores your receptors so they can even respond to a drug, so she still has to try and live well, but companies are taking on various strategies.  They're doing something quite ingenious.  I talked about that enzyme that holds the stress pathways in place.  They're working on medicines that allow us to have more of this molecule so we can say yes, I can remember this.  My lab, on the other hand, is working on understanding what's happening in prefrontal cortex which is often the opposite and seeing if we can stop the spine loss and these too much stress pathways and if we're lucky the exact molecules in one brain region and the other will be different enough that we can have our cake and eat it too.

(Peter) 
Now, I can hear viewers all over America asking one question other than what's your phone number.  Could you please call me?  The question is when?

(Amy)  
I'm hoping that over the next five, ten years we'll have some more choices.

(Peter) 
Let's pause for a minute before we even go any further and sum up where we've been so far.  In the future there may be more medical options for age related memory loss and even dementia, but in the meantime the same habits that result in a healthy heart - think about this - a good diet, regular exercise, they also promote a healthy brain and when you really think about this you're enhancing blood flow to the brain, oxygen to the brain.  That's where you want to be.  Now, Ellen leaves her doctor's office without her magic pill.  She's resolved to eat more healthfully, to exercise and to follow a particular recommendation from her doctor, which is to get involved with something she cares about.  Getting involved - you hear this all the time in this field.  Is there something called cognitive reserve?  Is that what we're talking about here?

(Aaron)  
You're born with a certain genetic predisposition to have good cognitive reserve whether it's intelligence, memory, whatever it is and then you can acquire things through your life experience and by doing that, by remaining intellectually active and involved you're adding to that bank.

(Peter) 
Ingrid Bergman was quoted as saying that happiness is good health and a bad memory.

(Amy Arnsten)  
She didn't have to live now.

(Dr. Peter Salgo) 
Let's add some texture to what you said which is as you grow older some things do get better.  Perhaps you get more perspective.  You may get creative.  You get some wisdom going on and it's not always remembering the password to your e-mail account that's all that important.

(Glenn McGee)  
Peter, that is a really, really critical point.  A lot of this is pressure from other people to compete as though you were twenty-five.

(Peter) 
Let me stop you right here and sum up one more thing.  We live in a culture where multi-tasking and quick response is the norm as you pointed out.  Now, while these skills may diminish as we grow older there are functions that we may not have touched that even improve with aging - reason, wisdom, creativity, the Ingrid Bergman stuff.  So staying active, socially engaged, seems to help keep these functions intact.  I don't want to leave without acknowledging that this is a problem that you've been experiencing.  How are you doing?  You the patient now, how are you doing?

(Cathryn Jakobsen Ramin)  
I am doing much, much better I have to say.  The best thing that I could have possibly done for my mind is to write the book I wrote because it was extremely mentally challenging for me on an ongoing basis.

(Dr. Peter Salgo) 
I want to sum up some of the key things that we discussed.  First of all, as we grow older forgetfulness can be part of a normal aging process.  While normal aging may entail some neurological changes not every memory problem is a symptom of dementia.  That's important.  In the future there may be more medical options for age related memory loss and even dementia.  In the meantime the same life habits that result in a good healthy heart, regular exercise, for example, good diet, also can promote healthy brain function.  And of course we live in a culture where multi-tasking, quick response is the norm and while these skills may diminish as we grow older there are functions that remain untouched and may even improve with aging - reasoning and wisdom, creativity.  Staying active, socially engaged, helps keep these functions intact.  And of course our final message is this - taking charge of your health means being informed and having quality communication with your doctor.  I'm Dr. Peter Salgo and I'll see you next time for another Second Opinion.

 

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Major funding for Second Opinion is provided by the Blue Cross and Blue Shield Association; an association of independent, locally owned and community based Blue Cross/Blue Shield plans committed to better knowledge for healthier lives.