Getting Old With a Sense of Humor
Mom has been pretty much without language for five years now. Three years ago she would occasionally call out “Ken!” (Dad’s name) once or twice a week, but other than that, her speech was a non-stop running chatter of “geri geri geri fica fica fica mao mao” and the like. Mostly two syllable experiments in sound. Ah. Also, occasionally–and as far back as 2 1/2 years ago, she would respond to the declaration “I love you” with “too too too too.” We wrapped ourselves in that response–a definite sign of comprehension and reciprocity.
Today we don’t even get the “too too too.” But we do get eye contact and a nod, which is just as good as sign of comprehension.
For all the times I’ve felt a thrill at the connection still possible with Mom via language, I didn’t have a picture of how thrilling it was for her to know that she knew something until one day–about 18 months ago–when I took her to the bathroom. We’d been having a very hard time getting Mom to urinate. She’d hold it for eight, twelve, eighteen hours. We massaged her, waited in the bathroom with her, gave her tons of liquid in hopes of getting her to release the contents of her bladder–to no avail.
One day I sat her down and begged her to go. “Mom, go potty. Let it out. Just let it out, ok?” She leaned over and made a shooing motion with her hand and repeated, “out?” I said, “yes, let it out.” She looked at the door, repeated the shooing motion (toward the door) and said “out” with the most excitement I’d seen from her in a long time. She was ecstatic at the small bit of comprehension she possessed at that moment. She knew the word “out!” She knew the word–it’s meaning–and it gave her significance.
I suppose it was akin to the feeling Helen Keller had at the comprehension of the word “water.” It opened up the world around her; gave her instant availability to connection with other human beings; empowered her to have a “self.”
I ache for Mom and her loss of language and all that has gone with it. But thanks to her, I am richer now that I know the power I possess with a vocabulary. Comprehension via language is such a huge gift (sorry to disagree, post-modernists)!
Now, if I can just stall the loss I already feel creeping in…
I just finished reading Peter Whitehouse and Daniel George’s book The Myth of Alzheimer’s.
How dare you! you want to say when you first see the title. My mother went through hell with this disease, and you’re saying it’s all imaginary? HOW DARE YOU!
Then you read the book and understand.
I’m not sure I agree with the entire revision of the story of Alzheimer’s, but I did like the tenor of the book. It’s compassionate toward those who suffer from dementia and even more so toward those who suffer from the stigma of dementia. It is angry at Big Pharma—the machine that markets fear of dementia so they can sell their mostly ineffective drugs. And it is angry at the medical establishment that succumbs to that marketing—toward doctors who accept gifts (in disguise) in exchange for prescribing Big Pharma drugs to their patients.
Dr. Whitehouse stresses that he was one of the cogs in that machine. His research helped write the story of Alzheimer’s as a disease, and his advice was sought after by pharmaceutical companies as they worked to develop drugs like Aricept and Namenda.
He was part of the machine until he realized he had helped create a monster that now feeds on the stigma of dementia such that no one is allowed to age with dignity if aging includes any level of dementia. The stigma of dementia has been blown up so large that anyone with a tinge of it is considered finished. People are no longer a mixed bag of assets and deficits. Once a person’s memory starts to go, he has no value unless the “deficit” is “fixed.”
Dr. Whitehouse points out instead that even with cognitive deficits, human beings still have plenty of assets to draw from in living fully satisfying lives.
So what is the myth?
Yesterday Bloomberg Businessweek published an article titled Mouse Study Suggests Alzheimer’s-Linked Protein Can Migrate Into Brain.
The story is this: researchers took brain matter from mice that had beta amyloid plaque (were genetically modified to have such plaque), injected it into the stomachs of normal mice, and months later found beta amyloid plaque in the brains of the normal mice.
If all you read is the headline of this story, the conclusion is that the beta amyloid from the sick mice got into the bloodstream of the healthy mice and passed through the blood brain barrier to take up residence in the healthy brains.
But if you read to the end of this article, it is suggested that there could be all kinds of reasons the healthy mice ended up with beta amyloid plaque in their brains, such as maybe there is some chemical in the plaque brain sample that passes through the blood brain barrier and causes a chain reaction that produces beta amyloid plaque—which would negate the headline altogether.
Now, watch the news and see how many people with take only the headline of this story and pass it off as scientific fact.
The moral of the story: be careful what you read and how you read it.
My last post on niacinamide and Alzheimer’s (it’s supposed to reverse Alzheimer’s de-mentiaThe Coenzyme nicotinamide adenine dinucleotide (NADH) has been used as medication in 17 patients suffering from de-mentia of the Alzheimer type in an open label trial. In all patients evaluated so far, an improvement in their cognitive dysfunction was observed. Based on the minimental state examination, the minimum improvement was 6 points and the maximum improvement 14 points with a mean value of 8.35 points. The improvement on the basis of the global deterioration scale (GDS) was a minimum of 1 point and a maximum of 2 points with a mean value of 1.82. The duration of therapy was between 8 and 12 weeks. No side effects or adverse effects have been reported from the patients or their caregivers during the observation period which is, in some patients, more than a year. This open label trial represents a pilot study from which no definitive conclusion can be drawn. A double-blind placebo controlled study is necessary
Trying to follow Alzheimer’s research sometimes feels like walking through an Escher exhibit: the contradictions can border on the absurd.
Take the new findings on SIRT1 and its relation to Alzheimer’s. Research after research shows that SIRT1 apparently protects against Alzheimer’s:
25 July 2010. The sirtuin protein SIRT1 is emerging as an important player in learning and memory, and may have potential as a therapeutic target in Alzheimer disease. Fresh on the heels of a July 11 Nature paper that demonstrated a crucial role for SIRT1 in memory (see ARF related news story on Gao et al., 2010), two new papers add to the growing body of evidence that SIRT1 helps keep brains healthy. In a paper appearing July 21 in the Journal of Neuroscience, researchers led by Valter Longo at the University of Southern California, Los Angeles, show that a SIRT1 knockout mouse has numerous defects in learning and memory. This finding implies that SIRT1 could have a protective role in AD, and indeed, in a July 23 Cell paper, researchers led by Leonard Guarente at the Massachusetts Institute of Technology, Cambridge, report that overexpression of SIRT1 can decrease Aβ production and the number of amyloid plaques in a mouse model of AD.
You’d think, then, that more SIRT1 is better for Alzheimer’s and less is worse. But:
Michán and colleagues also examined a transgenic mouse that overexpressed SIRT1 16-fold in the brain. On this normal mouse background, the authors found that this massive SIRT1 overexpression conferred no improvements in learning or memory, and that synaptic function was unchanged except for a slight increase in neuronal excitability.
And though less is worse, vitamin B3 in the form of niacinamide has been shown to “cure” Alzheimer’s in mice by decreasing the expression of SIRT1: Nicotinamide Restores Cognition in Alzheimer’s Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-PhosphotauWe evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD+-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated -tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. .
When asked about this contradiction, Dr. Greene, one of the researchers on this paper says,
You are correct – there are contradictions between the role of Sirt1 in AD. Regardless of these, nicotinamide has good effects in the preclinical models, and has been shown to now be effective for other neurodegenerative diseases as well. Sirt1 may be beneficial at some stages of the disease, and not others – we cannot [reconcile] these differences at this stage, but our research says that nicotinamide is highly effective in preclinical models and that inhibition of Sirt1 plays a role in these effects.
My mind wants to hyperventilate with the contradictions, but then I remember the story of the three blind men describing an elephant and realize the contradiction exists only because we do not yet fully understand.
And that’s what drives research onward.
Memory can be wonderful and cruel all at once.
It’s been almost a year since Dad died, and I’ve discovered that it takes a year to fully recover from the exhaustion of caregiving. It takes a year to recover fully enough to crave the chance to do it a second time over—to do it right this time.
Last Thursday was one of those gorgeous days that make your spirit soar. It was just warm enough, just breezy enough, just relaxing enough, just full enough of good plans that I wanted Dad here to enjoy it with us. I was in the middle of a supermarket parking lot when that thought came to me, and it was the beginning of a four-day breakdown.
Why can’t I be given a second chance? I’ve got all my energy back now, and I swear if I’m allowed, I’ll show Daddy all the tenderness that I had no time or energy to give him before. Why did he have to die before I recovered my ability to love him?
It was a catch-22 I battled with all weekend.
That Thursday evening I drove over the mountains to attend the licensing of a young preacher. I took advantage of the lonesome drive to listen to a book on tape my niece lent me. The title was “My Life in the Middle Ages.” It was supposed to be funny. Turns out the first two CDs were all about this guy’s father’s declining months. It was about death; about tying up all those messy loose ends.
Of course I bawled my way through that. When I couldn’t take it anymore—when I thought I’d better get my face in shape for the licensing ceremony—I popped in an Ingrid Michaelson CD. Quirky, upbeat Ingrid. Problem is, I’d never really listened to some of those songs before. About the fifth song on the CD is about the inevitability of death. “We are all snowmen, and we’re going to melt one day.”
The same message is being pounded into me over and over.
We’re all snowmen, and were are going to melt one day. It’s the norm. It’s not a devastating tragedy.
But the point of it? The point of living and dying and leaving others behind to bawls their eyes out?
Here I was, the daughter of a preacher, going to the licensing ceremony of a young, vibrant, new preacher, and I wasn’t getting it.
The point of living and dying, it slowly sunk in, is to pass on the baton. The best thing we can do is to spend ourselves living, then die and offer the lessons of our lives as rich mulch for the next generation.
It made me think of all the lessons I absorbed from Dad’s life. Like:
- Nature is awesome
- Don’t spend what you don’t have
- Prayer changes things
- God is gentle
- Invest in people on the fringe of society; they’re the ones who will remember you
It was a good weekend to mourn and know that there is good in all of this.
From now on, when mourning strikes, I will try to add to the list of lessons learned.
And I will think about how my life will have an impact after I—like all of us will—eventually melt.
The Alzheimer’s Research Paradigm
If you’ve every studied philosophy of science, you’ll recognize that current research in the field of Alzheimer’s Disease is battling paradigms. The funny thing is, the Alzheimer’s field hasn’t even reached the level of robust theory, yet there is strife in the ranks of researchers fighting over the direction inquiry should take:
“Kill the amyloid plaque!”
“No, viva le beta amyloid!”
“Forget amyloid. It takes tau to tangle.”
“Ha! The biomarker emperor has no clothes!”
“Wait. Isn’t it all about insulin resistance?”
“Nix all the above. Just get quality sleep, and you’ll be fine.”
If you think this is funny, these basic statistics will sober you up:
* As of 2010, there are 5.4 million people in the US with Alzheimer’s
* Almost half the people over 85 have Alzheimer’s
* When the baby boomers come of Alzheimer’s age, the costs of care for this disease alone will cripple Medicare and Medicaid
* Federal funding for research into a cure is dropping fast
* YOU will be paying for either your own care or for that of a loved one if a cure is not found. And YOU will either be grossly neglected when this disease hits you, or you will die the slow death of stress from caregiving for someone else.
Bottom line: research into Alzheimer’s—its cause(s), treatment, and cure—is alarmingly urgent and terribly underfunded.
There are plenty of people out there who believe we shouldn’t put money into research at all, because so far nothing has been found to stay the course of “Alzheimer’s” dementia, and the whole drug industry is just a ploy to line the pockets of the pharmaceutical fat cats. If you’re in that group, you can stop reading this now. If, however, you would really like to see your Mom or Dad or Yourself able to have a meaningful conversation with your loved ones and know whom you’re talking to—hopefully for the rest of your life—read on, because the question isn’t whether or not to research. The question is where do we put our research dollars?
Not a simple answer when you consider that the reigning paradigm for Alzheimer’s research is serious question.
Let me explain with recent findings from my own readings:
A couple weeks ago I attended a Cure Alzheimer’s Fund webinar presented by Dr. Rudy Tanzi (of Massachusetts General’s Institute for Neurodegenerative Disease) on Alzheimer’s research and drug development.
Beta Amyloid: Clues From Our Genes
Dr. Tanzi’s group is in the “clues from our genes” pool (looking at the genes as a starting point rather than, say, looking at diet first). The dominant belief in this pool up until recently is that beta amyloid plaque accumulation in the brain, followed always by tau tangles, are the two main biomarkers for Alzheimer’s Disease. That is, where there is Alzheimer’s, there is an overabundance of beta amyloid plaque and destruction caused by tau in the brain. Also, a higher load of plaque correlates with a higher degree of dementia (see slide from webinar). Plus, as this accumulation progresses and moves to different parts of the brain, there is a parallel manifestation of symptoms.
The connection seems pretty obvious. And Dr. Tanzi certainly has the credentials: back in the 80’s when he was studying Down’s Syndrome, he realized they had isolated the gene responsible for amyloid “plaque” deposits in the brain, and—given that all Down’s Syndrome sufferers end up with Alzheimer’s—thought to make a link between this gene and other cases of Alzheimer’s. From there it was one success after another, with Dr. Tanzi participating in the discovery of three of the four known gene mutations causing early-onset Alzheimer’s (these are the genes that guarantee you will get Alzheimer’s). Granted, early-onset AD accounts for only 5% of Alzheimer’s cases, but it does give weight to the conviction that Alzheimer’s has a genetic link. More recent studies looking at family history suggest that up to 80% of Alzheimer’s cases are genetically influenced (see slide from Tanzi’s presentation).
The presentation is convincing enough until you start reading the commentary in the field and start learning that current direction of research into the causes of Alzheimer’s is highly questioned.
Researchers coming on the scene today, for example, would argue that the plaque theory is circular reasoning. You can’t say that plaque leads to Alzheimer’s if you first define Alzheimer’s as “dementia with plaque.” And when your theory states that plaque accumulation leads to Alzheimer’s, the automatic null hypothesis is that where there is plaque (in copious amounts) you will always find dementia, and when plaque is cleared, dementia will go away.
But this has not born out. It is now known that “roughly one-third of all elderly adults have such plaques in their brains yet function normally.” It has also been proven that the elimination of beta amyloid plaque (achieved by the “Alzheimer’s vaccine”) does not cure dementia.
Thus the paradigm shake-up. Why continue with the biomarker research when the facts don’t bear an airtight connection? Is the “clues from our genes” group too heavily invested financially and psychologically in this line of research (as some suggest) to give it up as dead?
Dr. Tanzi responds to these fears in his recent presentation. He didn’t use the word per se, but nuance was the main come-back. All theories undergo refinement, and this plaque-causes-dementia theory is no exception. Looking at the genes may have lead to wrong conclusions in the past, but there are still some pretty interesting clues to follow going forward.
Here is a crude rendition of the protein-level pathology in Alzheimer’s:
Beta amyloid (Aβ) is cut off from its precursor protein; Aβ links to other ab in small clusters; Aβ kills nerve synapses; Aβ accumulates into plaques
For the past twenty years, research has focused on improving the symptoms of dementia by eliminating the final clusters of beta amyloid (plaques). Looking at the little diagram above, different drugs targeted the beta amyloid at different points on the linear progression toward plaque: Flurizan targeted the process that snipped the Aβ off its precursor protein; Alzemed tried to block the aggregation of Aβ; Dimebon was designed to protect the neurons from Aβ; one drug successfully immunized the brain against Aβ (resulting in clearance of plaque from the brain, inflammation in the brain, and progressive dementia); and finally, drugs were developed (Aricept and Namenda) to act at the symptomatic level.
None has had any significant effect on the brain’s function in memory tests.
Tanzi’s response? Perhaps the reason drug trials fail is that the potency of the drug is off—either too weak or too strong—and funding for a subsequent trial is cut off. Or perhaps researchers need to stare at the diagram a little longer and find out whether beta amyloid needs to be left to do some mission, then cleared before it wreaks havoc on the synapses.
Which is exactly what happened with Dr. Tanzi—a little stroll through the lab, a light-bulb moment, and Tanzi discovers that beta amyloid kills bacteria and yeast like nobody’s business. Beta amyloid is a good guy? The plaques themselves are just “a field of bullets” left over from some major battle?
Definitely worth an investigation. A new direction.
To Fund Or Not to Fund
So it turns out that looking at clues from the genes is not a paralyzing avenue of research after all. Is the paradigm really dead, or just needing refinement? In the new direction of Alzheimer’s research, Dr. Tanzi’s findings have lead to a more recent drug (PBT2) that takes the “antibiotic” role of beta amyloid into account as it tries to clear its toxic leftovers. Do we pull the plug on funding just when the story is getting really interesting?
The competition out there is fierce. You would think from some of the stinging accusations aimed at the “old school” research that funding for groups such as Tanzi’s should be questioned. Yet, as the webinar pointed out, “the vast majority of our knowledge about AD and AD drug discovery has been based on studies of the four known AD genes over the past two decades.” That’s old school success.
On the down side, “about 70% of AD genetics is unexplained by the four known AD genes.” On the further down side, it’s going to take A LOT of funding to find the genetic culprits for the rest of Alzheimer’s cases. And genetics is still only one of several approaches to studying this disease! (Besides, paradigms don’t die until a better one supersedes it, and there is no airtight theory out there yet).
Do we put all our eggs in one basket? What if there aren’t enough eggs to spread around to the different baskets?
Frankly, I don’t know the answer to this question.
There are a couple good reasons I think the Cure Alzheimer’s Fund group is worth supporting, though. One reason is the Cure Alzheimer’s Fund website itself. The Internet has plenty of faults, but it also has the advantage of open criticism. If you look at the comments sections of one of the papers put out by Tanzi’s group on the Alzheimer’s Forum, you’ll see an open debate. It’s free collaboration. It’s crowdsourcing at its best. I think it multiplies the value of your funding dollar.
Another reason is that I’ve suspected my own mother’s caseStay tuned for a post on this topic to be of possible bacterial/fungal origin and am dying to see what this group finds in their new line of research. The only thing I fear is the psychological barrier to this new approach.
A Taboo Research Project?
To be specific: the two agents being considered by Tanzi’s group as possible aggressors in the beta amyloid battle are Chlamydia and Candida Albicans. But looking at Candida Albicans as a possible cause of anything is TABOO in mainstream medicine. Just browse the comments section of a recent article in the New York Times about Candida Albicans, and you’ll see what I mean.
Will Tanzi’s group have the courage to fight all the enemies of research at the same time: tainted motives (the desire for personal glory), psychological entrapment (continuing in a line of research simply because it’s been going on for so long), and mainstream opinion about what is acceptable research (we do not look at X)?
I guess it’s going to take a lot of money to find out. Which brings us back to the basket issue.
Do we have to duplicate Alzheimer’s research at the Federal and State levels? The state of Texas, for example (being one of the top three states that will go broke paying for Alzheimer’s care in the future), is spreading its research egg money into several baskets:
* Prevention and Brain Health
* Disease Management
Why repeat this with every state, plus private groups on the side? Is there a way to get more collaboration between research groups? The well of needed funding is infinitely deep, so why are we digging multiple wells?
I guess part of the answer is that individual motivation for research (even if it is for personal glory) is the strongest kind you can find, and therefore the best engine for finding a cure. And likewise, education plus individual conviction will drive donations. There is certainly enough information available at one’s fingertips to give no one who is interested in a cure an excuse to sit on the sidelines!
So what will you do?
Because where there is a will, there will be a way to end the increasingly long goodbye.
For further reference:
Beta-Amyloid: An Antibiotic? (with a slew of interesting comments)
Alzheimer’s Brain Tangles Offer Clue To Worsening
Alzheimer’s Disease: No End to Dementia
New Potential Cause of Alzheimer’s Disease Detected
Alzheimer’s Scary Link to Diabetes
Follow the Alzheimer’s Breakthrough Ride journal
An video report on several intriguing theories of Alzheimer’s.
Funny how that commercial for Pristiq antidepressant gets it wrong. The last thing in the world we Alzheimer's victims (on both ends) need is a big old hand winding us up even more! Yikes! A better image would be seeing that key spin in the opposite direction, letting that purple-clad lady relax completely. Now there’s a pill I'd buy!
It’s ads like that that take me back to Princess Bride and Wesley’s pronouncement: "Life is pain, highness! Anyone who tells you otherwise is selling something." A lot of people have to put up with a lot of pain. It's not just us.
So perspective helps some.
Here are some other things that help:
Yesterday I finished reading Still Alice. I think the title is meant to be a loaded question. Can I, after losing all memory of others and self, still be considered to be myself? Am I still “me” if I don’t have a clue what that me is or was?
The fictional book answers the question affirmatively.
I found myself examining my perceptions of Mom–who obviously no longer knows herself–and thinking the conclusion was absolutely true. I still recognize Mom in this shell of a person. She still has the same mannerisms, exudes the same kind affection, displays the same funny reactions. She’s still Mom down to the core.
But not so much with Dad–a victim of Parkinson’s. It seems I recognize him less and less. But then, I suppose I’m holding a higher standard of “self” to Dad, giving that I’m assuming he’s more “there” than mom. If I were to strip him down to mannerisms alone, I would probably find him to be his old self too. It’s a tricky question.
At the very end of the novel, Alice has a moment of lucidy and says, “I miss myself.”
That statement struck me to the core. You know why? Because I miss being me too! There is this incredible longing inside me to be “more” or “better” or “fuller” or something. I fall way short of the me I want to be, and I long for (or miss) that. Yet I still want to be treated as though I were fully “me” even though I don’t meet my own standard for myself.
Why not, then, treat the Alzheimer’s victim as though they were fully themselves, regardless of how short they fall from the perfect version of that self?
Ultimately, our longing is for acceptance, love, safety. Let’s just make a pact to offer it unconditionally to each other regardless of where we are on this journey toward the perfect self.
Alzheimer’s and the Ego: the Power of No
All my life I considered myself an introvert, a private person, ungifted in the art of validating people.
In my early forties (a couple minutes ago), I bought a small restaurant, and all this changed. I grew by leaps and bounds in my fascination with people of all stripes and in my ability to dig beneath the surface and find the gold within. I grew in my ability to remember names, know faces, discover connections, and find new ways to validate people. I got high on it—on my ability to validate. It validated me in return.
Then one day this abruptly ended. I crashed. I had been working seven-day weeks for two and a half years, and my body and mind couldn’t take it anymore. The first scary sign of stress was when some of the music I played every day at the cafe lost its familiarity. I was evidently unable to learn new music. Then it was faces. New ones wouldn’t stick, and old but infrequent ones were a struggle to recall. I was filled with doubt when in conversation: what had we talked about the previous time? Did they just come from Europe, or were they going to Europe? I couldn’t remember.
Stress fried my brain, and my validation skills went with it. Nothing, but nothing hurt as much as having a newly-made friend appear and me not know who they were for ten or twenty seconds. The eager look on their face faded instantly, and nothing could bring it back. No amount of remembering in a few seconds would make up for my initial inability to validate them. I died a little bit every time it happened.
I wanted to resign from life. Retreat. Embrace my pre-cafe, introverted self. I wanted to be given a chance to explain (there is no such thing). I cried, prayed angrily, tried to bargain with God.
How do you love people when the principal organ of love—the brain—is shot?
I realized eventually that I was mourning my ego, not my lost ability to validate people—because I hadn’t lost the ability. I’d only lost the ability to do so in a way that would make me look good. There were and are plenty of opportunities to extend kindness and touch people’s souls even if we can’t immediately recall a face. It just takes an awful lot of something to give up the craving for reciprocity.This also showed me that validating was not my natural gift. To meet someone for whom it is, you must meet Jan Petersen. This afternoon I watched the video Jan’s Story: Love and Early-Onset Alzheimer’s again and re-discovered a true hero. Even with severe dementia, Jan knows how to seize each day and touch each person she meets. Jan’s is both a heart-wrenching and heart-warming story. Many people go through life mentally intact yet unable to see the goodness that surrounds them. Then you meet someone like Jan whose indomitable spirit sheds significance on everything and everyone she sees—regardless of her inability to name things.
The validation breakdown begins with us who think Jan’s story is nothing but a tragedy. But I tell you, if I could pick one trait to take with me on the dark road into oblivion, I’d pick Jan’s ability to validate without requirement; to love without strings attached; to milk each moment and each encounter.
That is the validation breakthrough!
Here are four more of my current heros—people with early onset Alzheimer’s who put themselves in the crosshairs of the stigma-tazers so they can help the rest of us see a little bit of the road ahead:
Here’s what happened: I’m not a “from scratch” web coder, so I installed what’s called a “theme” for my niece’s website and used it as a springboard to create a look that would capture her life and style.
A lot of work goes into designing the look of a website, but it has to pale in comparison to all the work that goes into creating themes, or “platforms” on which creative designs are based. By the time I get my hands on designing a website, all the hard prep work has been done, and I’m presented with a lovely spring board that allows me to jump and flip and fly wherever my creative juices lead.
The U.K. recently decided that Aricept and other acetylcholinesterase inhibitor drugs can be prescribed for mild Alzheimer’s cases (in addition to moderate cases. See article U.K. Reverses Stance On Alzheimer’s Drugs NICE is now recommending that three drugs known as acetylcholinesterase inhibitors—Aricept from Pfizer Inc. and Eisai Co.; Reminyl from Shire PLC; and Exelon from Novartis AG—be considered for use in patients with “mild” forms of Alzheimer’s, in addition to the patients with “moderate” forms of Alzheimer’s for whom NICE previously endorsed the drugs.). The more obvious reason is that these drugs should be getting cheaper once their patents expire, and therefore easier on the state’s prescription coverage budget. The less obvious reason is the relative ignorance Brits have regarding the sport of baseball.
First, you have to know how neurons and neurotransmitters work. Here is a short animation that shows how neurotransmitters work in the brain:
The cycle is a fantastically efficient one. Neurotransmitters are shocked into action, released into the synapse where they interact with receptors on the other side of the synapse, then swept up to make room for the next wave of neurotransmitters.
In Alzheimer’s, the favorite neurotransmitter tagetted by drug companies is acetylcholine because it is crucial for the formation of new memories. In the Alzheimer’s brain, there is an increasing shortage of acetylcholine, making it harder and harder for the brain to form new memories. The enzyme that recycles acetylcholine is acetylcholinesterase. What Aricept (an acetycholinesterase inhibitor) does is inhibit this recycling process, so the neurotransmitters hang around longer in the synapse and interact more often with memory-forming receptors.
Here is a video of a different neurotransmitter (serotonin) and its recycling inhibitor. It’s a good picture of the process that takes place with acetylcholine and acetycholinesterase inhibitors:
All of this is easier for Americans to grasp, because it can be compared to baseball: in baseball, players are stored in the dugout, called into action on the field, then recycled back into the dugout when their action is no longer called for.
Suppose that a team were to lose all but four of its players. Someone would have to block the dugout so the players wouldn’t sit back on the bench but rather take up the bat once more.
The players are the acetylcholine, the rule that sends them back into the dugout is the acetycholinesterase, and the person blocking the dugout when there is a shortage of players is the acetylcholinesterase inhibitor.
This also, by the way, illustrates why Aricept et al eventually fail: the four players get tired of playing the whole game all season long and quit.
Someone must have finally explained baseball to the Brits.
Like the title of this blog says, there are things to be learned from all kinds of dementias. Here is a particularly astounding thing to learn: severe autism does not necessarily mean the sufferer is mentally retarded. This video will shock you into looking beyond the outward appearance of those who cannot communicate and into the soul.
Sometimes I wonder how much like this girl my mother is. How much does she really know about what’s going on around her?
Here is something frustrating about clinical trials of Alzheimer’s drugs: the FDA requires that such trials show an almost immediate improvement in memory tests of participants in order for the drug to get approval, disregarding improvement in other symptoms, and consequently derailing a possible cure for this dreaded disease.
Here is why I think there is an inherent problem with this guideline:
If you go the the Alzheimer’s Association website and take the interactive tour of a brain with Alzheimer’s (a fantastic tool!), you will notice that there is a general pattern to the progression of Alzheimer’s and its accompanying symptoms. Specifically, looking at slide 13 you will see that the first part of the brain to be affected by Alzheimer’s is the inner core where the hippocampus resides—that part of the brain responsible for short-term memory. From there, damage spreads outwards to the cortex of the various lobes. As the second image in slide 13 shows, the Frontal Cortex is affected in mid stages of Alzheimer’s. This area is responsible for attention, social skills and intelligence (or wit). It is associated with “personality.”
Now, if an effective drug for Alzheimer’s were to be developed, you would expect to see the least damaged areas respond first, followed by the most heavily damaged areas.
Such were the preliminary results of the clinical trial of Dimebon. In reading the various anecdotal accounts of the Dimebon trial (see Bob DeMarco’s piece on the Alzheimer’s Reading Room), the results seemed to show precisely this initial response: Alzheimer’s sufferers reported increased alertness, social skills, and wit. Here is a sample quote from the various testimonials:
The major drug companies are focusing on memory. Are they after the right target? I’ll tell you this, in weeks 6 through 18 in the Dimebon clinical trial my mother was more engaged with me, more aware of her surroundings, more interesting, and more like her “old” self then she had been in six years.
The least damaged areas of the brain were affected in the 12-week trial! Then the trial was stopped because the inner (most damaged) area of the brain showed no marked improvement.
Would it not make sense to glean from the trial that a logical reverse course of the disease was set in motion and to continue it to see if the pattern held?
Pfizer et al, could you give us another 12 weeks when studying Alzheimer’s please?!
[Note: this analysis is mine alone. It may not be true that the least affected areas would show improvement first]
Anyway, ever since my sister-in-law’s mother was taken to the doctor with signs of Alzheimer’s and discovered to have nothing but dehydration, I’ve been meaning to read up on how exactly the lack of water hinders brain function.
Here’s what I found about dehydration and the aging brain:
Not much—unless you count articles on websites trying to sell water filtration systems.
The fact that water makes up 70-80% of a nerve cell and transports both nutrients and wastes from neurons means it is essential for proper brain function all through life. That’s a given. What’s not a given is how much a brain has to be depleted of water to affect cognition.
Rigorous research on the topic of the brain and dehydration is limited. Even the “standard facts” about the body and water are all over the place: babies come out of the womb composed of 90% water; no, 78%; no, make that 70%. In adults, the proportion is 60% water for males and 55% for females. The consensus is 50-60% for adults in general. The brain is 60% water; nay, 90%. Whatever.
As for how much water you need to drink on a daily basis to be properly hydrated, oy, there is no consensus. For years I’ve been hearing “8 cups a day.” No allowance for a sedentary life or for someone with a diet of fruits and vegetables (which are high in water content); no penalty for eating junk food (which would increase the need for the detoxifying properties of water) or for spending days cooped up near a wood stove.
One article quoted the Mayo Clinic as saying that “the average adult loses more than 80 ounces of water every day through sweating, breathing, and eliminating wastes,” and therefore you’d have to drink 10 cups of water/day to rehydrate. I searched for the quote on the Mayo Clinic site and didn’t find it. Instead, I found a recommendation for 6-8 cups of water per day.
Suppose you take the most conservative recommendation of 6 cups per day–do you follow that? I don’t think I’ve ever gone one whole week drinking that much per day.
It has been estimated that 75% of Americans are chronically dehydrated. OK, that figure is questioned. But it seems to be a fairly hard fact that “among people over 65, dehydration is one of the most frequent causes of hospitalization.”* Understandable: throw in a bit of incontinence, and fear of hydration soars. Also, some medications are diuretics, and after 50, the body loses kidney function and is less able to conserve fluids.*
But how bad is dehydration for your brain?
According to Lumosity, when your body lacks water,
brain cells and other neurons shrink and biochemical processes involved in cellular communication slow. A drop of as little as 1 to 2% of fluid levels can result in slower processing speeds, impaired short-term memory, tweaked visual tracking and deficits in attention. With proper hydration however, neurons work best and are capable of reacting faster.
But pinning down the exact link between hydration and cognitive function is tricky in the lab. From Hydration and Human Cognition:
Although adequate hydration is essential for optimal brain function, research addressing relationships between hydration status and human behavior and cognitive function is limited. The few published studies in this area are inconclusive and contradictory. The impact of variations in hydration status, which can be substantial as humans go about their daily activities, on brain function and behavior is not known and may impact quality of life.
From PubMed’s Hydration and Cognition: a Critical Review and Recommendations for Future Research: “The limited literature on the effects of dehydration on human cognitive function is contradictory and inconsistent.” The monkey wrench in research here is given as confounding factors:
Confounding factors, such as caffeine intake and the methods used to produce dehydration, need to be considered in the design and conduct of such studies. Inclusion of a positive control condition, such as alcohol intake, a hypnotic drug, or other treatments known to produce adverse changes in cognitive performance should be included in such studies. To the extent possible, efforts to blind both volunteers and investigators should be an important consideration in study design.
On the Mayo Clinic site, a Dr. Lette finds that “there’s no scientific evidence that drinking large amounts of water is good for one’s health.” The recommendation in this article is to drink when you’re thirsty, and that’s enough.
My question is, does the lack of scientific evidence mean there is no scientific proof or merely that there is no motivation to research the topic to obtain the evidencef? Who, after all, would fund research into water being fundamental to the health of the aging brain? Not the pharmaceutical industry. If you could avoid dementia by being continually hydrated, you wouldn’t need pills to fix dementia. Why would any self-respecting drug company fund that finding? And if it takes a lot of money to work through all the confounding factors, who’s going to pay for it?
The thing is, when the anecdote about my sister-in-law’s mother is not even rare, it makes me wonder how many cases of Alzheimer’s are checked for a history of dehydration. I don’t mean just the over-the-weekend kind of dehydration, but long-term, chronic shortage of water.
As with Mom. The list of things Mom was doing “right” for her aging brain is stellar: she was highly educated, spoke multiple languages, was given to prayer and meditation, was active in the community, etc., etc. Yet she succumbed to complete dementia in her early seventies! Could it all have been due to her severe distaste for water? I mean, she hated water–would gag if she drank it straight from the tap. Could her present dementia have been prevented by a regimen of 4+ cups of plain ole water daily?
I hate to look at the “what if” from Mom’s point of view, but for our generation and beyond, it needs a good deal more consideration than we’re giving it.
What do you think? Am I grasping at straws? (I suppose that’s OK as long as the straw is propped inside a nice glass of water, right?).
Water and Brain Function
Water in the Body”
You’re Not Demented, Just Dehydrated
Dehydration and Cognitive Performance
Hydration and Cognitive Function in Children
Nerve and Muscle Cells
Impaired cognitive function and mental performance in mild dehydration
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