Yesterday I came across Lewis Carroll’s “Jabberwocky” poem in Alice in Wonderland (you can download the whole book for free at Gutenberg).

I’ve always loved how Carroll made nonsense words sound like language. But what got me this time around was Alice’s response, and the parallel of that with how I feel about “talking” to Mom.

Here's a fun little fact about joint caregiving: it can turn a tiny disagreement into a full-blown I'll-move-to-the-North-Pole and you-move-to-Antarctica fight. The constant demands, the inability to comprehend half of those demands, the lack of time off, lack of perspective and sundry other issues will wind the coil so tight that a slight breeze or feather of conflict between those sharing the caregiving responsibilities can cause a mighty painful snap.
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:

• A good cup of coffee in the morning
• Music (it's amazing how music can change the mood)
• A five minute sit on the porch
• A hot shower
• A good cry
• Painting
• Blogging
• A long primal scream

One thing Parkinson’s can’t take away from a man is all he has passed on in his lifetime. Here is Dad, rock-hounding Parkinson’s style. The fact that he can’t stand up on his own or kneel and claw through the dirt to get to the jasper or petrified wood doesn’t detract from the fact that he instilled the love of nature and science in his children. It’s in our blood now to visit all the national parks we can and to dig for fossils wherever there be beds.
He’s taught his children so many good things, and Parkinson’s can’t take that away from him.

Crosby, Stills & Nash, “Teach Your Children Well”

After writing my last post regarding the stress of caregiving, I had to drive somewhere, and in the course of the short trip, I caught a clip of a Haydn symphony on the radio. I don’t know how, but there are sections in there that make me feel as though this exhausted, shriveling heart of mine is actually quite expansive and able not only to cope, but to bring beauty out of the brokenness around me. You know how sometimes you see a scene or a photograph that makes you certain that the universe is true and right and good? Well, music does that, but with thrice the emotion. Music can rewire a frazzled or finished outlook into one of hope. And hope can take you a looooooong way down a very dark road.
All to say that music—in addition to being a fantastic tool for treating Alzheimer's—is a very inexpensive way to get your groove back when you’re done in from caregiving. Or from living a regular life-is-pain-highness kind of life.
To prove this, I'm giving you a little tool in this post that some people may not know about. The tool is called Pandora—an internet service that lets you create your own radio station online.
The extra cool thing about this service is that you can create multiple radio stations, all with different moods—colored by different genres or artists—to suit your changing needs. Sometimes I don't even know what my need is or what it is that will trigger a brighter outlook, so having multiple "moods" to choose from is very useful.
Cutting to the chase, here are four stations I created to get you started. Click on any one of them and follow instructions to log into Pandora. From there, you can tweak the station by "adding variety" (a specific music piece or musician) to the station. You can also "thumbs up" or "thumbs down" any piece that you hear, and the station will remember to pick similar music or not to play that piece in the future. Talk about tailored just for you!
So here goes—four different flavors for your listening pleasure:

Jazz. You know, the good stuff with Stan Getz and Louis Armstrong and Bobby McFerrin and Michael Buble…
This is a fusion of old hymns and contemporary Christian pop. Nice, especially for Sunday mornings.
My personal favorite: spicy Latin mix. Makes you want to jiggle and dance and go crazy! A great stress-reliever.
Classical is music to transport the soul.

A couple more tips: if you want to play this music off your sound system without leaving the kitchen table, you can buy a $4 wireless FM transmitter and send the station to your main tuner. You can also "send the station" to the radio that sits on your mother's side table in the bedroom while you’re working on the laptop in the kitchen. Just a whole lot of things you can do with Pandora!
Do have fun, and come back and post a station of your own creation if you dare!

I’ve had water on my mind lately (which is not the same as, but does not preclude, water on the brain).
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?).

Resources:
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

I’m having a hard go at it with my new resolution to spend more quality time with my mother.

It’s a very painful fact that I miss Dad and that I wish I had spent more “being time” with him instead of dividing my time between being and being productive. As I’ve mentioned before, in hindsight, all you want is to be near the one you’ve lost just a few more minutes. Nothing else matters but being in the person’s presence and having them know you are there.

I want to do this with Mom, but Alzheimer’s presents a huge problem. Whenever I see Mom sitting alone, it kills me because she looks so terribly alone. So I go sit with her, and on a good day—most days—she is riveted with my presence. But the second I leave her sight—to fling clothes from the washer to the dryer; to use the bathroom; to make a cup of tea—she is completely alone again. And in those moments—from her perspective—she has always been and always will be alone. There is no memory of my having been in her presence all morning other than a few moments of necessary “productive time.”

I hate this disease. There is no sufficient quality time you can give someone with Alzheimer’s. As a caregiver, it feels like there is no neutral status for you as a human being: you are either benevolent or malevolent; sacrificial or selfish; worthy or worthless.

Alzheimer’s isn’t a one-man disease; it does a pretty good job of spreading the pain around.

More on the brain’s default network:

The default network in the brain is considered a “second brain” because it turns on when the rest of the brain is at rest, and turns off when the rest of the brain is at work. Normally, that is. As people age, the default network is less and less capable of shutting down when the mind is concentrating on some difficult cognitive task as it would do in a younger adult’s brain. Since the default network uses 30% more resources than the rest of the brain, you can see how the resources available for cognitively challenging tasks decreases as we age.

In Alzheimer’s, you get the extreme case of this aging effect: the default network doesn’t shut down at all when it’s supposed to (same as in Schizophrenia–which is probably why they use antipsychotic drugs meant for Schizophrenia in Alzheimer’s patients) until that part of the brain eventually dies.

The default network is not very developed in children. It gets more active as we grow into adulthood. That makes me wonder if language is the software that runs the default network. Think about it: the default network is the part of the brain that sorts, categorizes, and edits/deletes memories, and language is the software that sorts, categorizes, and edits/deletes meaning. With language also comes prejudice, and prejudice does not exist in the very young. Also, in Alzheimer’s the default network eventually atrophies, and language ceases (just further argument that the default network is inextricably tied to language).

All of which brings me to the point of this post. Last week there were articles all over the news saying that having more than one language guards you against the worst of Alzheimer’s. Mom spoke four languages and fell prey to Alzheimer’s in her sixties–with no family history of early Alzheimer’s. Dad spoke three
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AC6BTV7AQCKPToday I stopped at a light and to my right was a truck hauling what looked like a small, complete house all wrapped in white plastic. I wonder if it was one of these “Granny Pods” that are becoming a hit all over the country. I don’t know what people are bellyaching about. I think these are a great idea! It would be like playing house and you wouldn’t have to put up with any teenagers blaring music from their room as you would if you lived in the real house. Think I’ll order one with a Japanese soaking tub when I get around to needing one.
AC6BTV7AQCKP

In my research on Alzheimer’s and glucose metabolism, I ran across a fascinating article about the brain’s default system–that part of the brain that is affected in Alzheimer’s Disease; that part of the brain that hogs glucose like no other part of the brain.

In The Secret Life of the Brain, Douglas Fox brings together research on the default network beginning with Dr. Sokoloff who, in his attempt to find out why the brain uses so much glucose (20% of the body’s supply), discovered that the brain uses as much energy while “at rest” as it does while performing tasks.

Later, a neuroscientist named Marcus Reichle discovered a kind of “brain within the brain” that works its butt off when it’s supposedly in “idle mode.”

Raichle and Shulman published a paper in 2001 suggesting that they had stumbled onto a previously unrecognised “default mode” – a sort of internal game of solitaire which the brain turns to when unoccupied and sets aside when called on to do something else. This brain activity occurred largely in a cluster of regions arching through the midline of the brain, from front to back, which Raichle and Shulman dubbed the default network (Proceedings of the National Academy of Sciences, vol 98, p 676).

It was found that some parts of this network devoured 30 per cent more calories, gram for gram, than nearly any other area of the brain. Since part of this default system is in constant communication with the hippocampus (which records every day memories), Reichler speculated that its function was to sort, evaluate, and categorize memories in such a way that would allow the brain to use the past as an “inner rehearsal” for considering future actions and choices.

Brilliant. Just when you think daydreaming is a waste of time, it turns out it’s crucial for living.

Raichle now believes that the default network is involved, selectively storing and updating memories based on their importance from a personal perspective – whether they’re good, threatening, emotionally painful, and so on. To prevent a backlog of unstored memories building up, the network returns to its duties whenever it can.

In support of this idea, Raichle points out that the default network constantly chatters with the hippocampus. It also devours huge amounts of glucose, way out of proportion to the amount of oxygen it uses. Raichle believes that rather than burning this extra glucose for energy it uses it as a raw material for making the amino acids and neurotransmitters it needs to build and maintain synapses, the very stuff of memory. “It’s in those connections where most of the cost of running the brain is,” says Raichle.

Reichler later attented a lecture by an Alzheimer’s specialist and was shown a map of beta amyloid plaques (those clumps found in Alzheimer’s autopsies) in the brain. The picture looked exactly like the default network!

Raichle, Greicius and Buckner have since found that the default network’s pattern of activity is disrupted in patients with Alzheimer’s disease. They have also begun to monitor default network activity in people with mild memory problems to see if they can learn to predict who will go on to develop Alzheimer’s. Half of people with memory problems go on to develop the disease, but which half? “Can we use what we’ve learned to provide insight into who’s at risk for Alzheimer’s?” says Buckner.

That got me thinking…

Maybe one reason we lose memories is that our lifestyle doesn’t allow for much rich idle time like when we would sit on the porch sipping sweet tea on a hot afternoon. So the default network can never do its work of sorting and categorizing memories, and consequently we lose them.

And if this is a problem with the present generation, how much moreso for the upcoming generation. We are consumed with having something to pay attention to all the time. Just look at TV screens these days: not only do you have the main screen, but there’s the pop-up ad for the “next show,” a caption for what’s going on on the screen, and a ticker at the bottom of the screen for what’s happening elsewhere.

Maybe part of the solution for AD is the “quiet space” to be incorporated in school, at work, and at home. Hmm, come to think of it, I offered this very solution in a comment to an article in Time Magazine back in 09 (Turn Off, Tune In, Log Out):

I predict that the twitterification of our society is going to lead to an exponential increase in early-onset Alzheimer’s. We’re increasing the rate of input to our brains and decreasing the time for processing information, and our brains are going to revolt. That, in turn, will lead to the next big industry: de-twitterification rooms where you can sit alone and unconnected, with nothing but a giant aquarium and a beanbag. -Marty

SEE ALSO Language and the Brain’s Default Network in Alzheimer’s

I found this short documentary film yesterday while browsing another blog about Alzheimer’s. It’s in French with English subtitles and you can watch it for one euro online. Worth the euro and then some (you can click on the picture to go to the website). The film is done by the son of an artist with Alzheimer’s, and the documentary marries his own artistic and filial sensitivity well.
As an artist whose artistic mother also has Alzheimer’s, this movie hit home for me. It was like watching my own mother lose all her nouns, then her knowledge of interpreting nouns on a canvas, and finally her knowledge of self.
In this film, the mother’s sorrow and fear are mitigated by the son’s desire to hang out with her. I only hope his desire lasted beyond the making of the film. For the sake of all those with Alzheimer’s, I hope love lasts beyond the time the disease is an interesting artistic or scientific curiosity. I hope it lasts beyond the time a diseased person has anything at all to offer.

Just when we thought Dad’s Parkinson’s symptoms were a source of fear and despair, we saw potential for an up side to the down side.

I took Dad for a walk tonight. It wasn’t a long walk. Dad was tired and didn’t really want to go. But he acquiesced to my prompting, and we walked to the end of the 50-yard driveway.
The whole time we walked, I supported Dad’s right arm. And the whole time we walked, Dad’s arm shook violently. By the time we got back, my arm was buzzed and aching.
Then it occurred to me that if Dad’s energy gets passed onto me in this bad way, perhaps we could harvest the energy in a good way. I suggested to him that we design something like the soccer ball recently invented by those Harvard girls—you know, the ball that stores the energy of a game’s worth of kicking into a battery that can then be used to light up the Third World.
Dad laughed.
But hey, why not harvest the energy generated by Parkinson’s tremors? Maybe we could even wire the energy back into the brain for deep brain stimulation therapy.
There’s got to be an up side to the down side of this energy-depleting disease!

The other day I was having fun designing a blog for my pregnant niece, and it made me think a lot about operating systems and web platforms and hardware and software and the whole process of creativity and, as always, Alzheimer’s and Parkinson’s.
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.
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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.

RELATED ARTICLES:
Alzheimer’s and the Ego: the Power of No

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“Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer’s disease, the fragments accumulate to form hard, insoluble plaques.”!”
“No, viva le beta amyloid“Most people think abeta is junk,” a toxic byproduct of other activity in the brain, said Rudolph Tanzi, director of genetics and aging at Massachusetts General’s Institute for Neurodegenerative Disease. “This says tread carefully. It may play a normal, essential role in the brain and be part of the way the brain protects itself.”!”
“Forget amyloid. It takes tauThe appearance of elevated tau in CSF is important, but merely a reflection of the disease process. What is not at all touched upon and in fact routinely neglected in the press, is that the tau protein drives neurodegeneration in a very direct way, much more so than the beta-amyloid protein, which is the target of the cited study. In fact, without abnormalities of tau there is no Alzheimer’s disease. Many older individuals develop beta-amyloid deposits in their brains and never experience Alzheimer’s disease, another aspect generally not mentioned. Conversely, if only tau is abnormal, and beta-amyloid is not involved, there is always a terminal neurological disease. to tangle.”
“Ha! The biomarkerThe thing with biomarkers is that they only work/make sense if the biological processes behind a disease are fully or at least largely understood. Only then is it possible to choose a proxy (the biomarker) for the final result (optimally a cured patient). Since the processes behind Alzheimer’s (more generally in the CNS) are badly understood this area is not well suited for biomarkers emperor has no clothes!”
“Wait. Isn’t it all about insulin resistance?A new short-term trial of intranasal insulin in Alzheimer’s patients and people with mild cognitive decline showed benefits on certain memory and functioning tests”
“Nix all the above. Just get quality sleep,“Levels of the protein increased in mice during the night — when mice are mostly awake — and fell during the day when mice sleep. The longer the mice stayed awake, the more amyloid-beta levels increased, the team found. The team also measured amyloid-beta levels in the cerebral spinal fluid of some healthy young people and found the same pattern observed in the mice — amyloid-beta levels increase when people are awake and fall during 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 industryAnother new frontier for drug companies’ illicit profits. Vaccines, invented “syndromes” and now, allegedly predicting who will come down with what disease and medicating them for decades before the possible advent of that disease. With no certainty the disease will manifest this is pure sham. And the pharmas will profit double from their con job — think of the so-called “mind drugs” that will be prescribed to mediate the untold psychological effects on people given future death sentences regarding this or that disease! 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 who 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“It’s one reason why the so-called amyloid hypothesis, which holds that to cure Alzheimer’s you have to curtail Aβ, is in question these days: There’s little evidence so far that fighting Aβ leads to a functional difference to patients.” 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“No treatment is available to slow or stop the deterioration of brain cells in Alzheimer’s disease. The U.S. Food and Drug Administration has approved five drugs that temporarily slow worsening of symptoms for about six to 12 months, on average, for about half of the individuals who take them.” 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 originAt a speculative level, one alternative explanation would be that some cases of AD could result from a persistent CSF infection, or from a transient infection that went away but engendered a permanent Aβ response and its attendant immune modulation. 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:
* Science
* Prevention and Brain Health
* Disease Management
* Caregiving
* Infrastructure.

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.

The topic of fasting and Alzheimer’s has been on my mind lately because, well, Alzheimer’s is always on my mind and because recently a friend of mine got on this diet where you’re supposed to eat six small meals a day to trick your body into not storing fat.

Since intermittent fasting has been shown to slow body and brain aging, I wonder (the fat part aside) what this continual eating is doing to the brain.

From Psychology Today (2003):

It has been known for years that sharply restricting the calorie intake of laboratory animals increases their life span. But a new study by researchers from the National Institute on Aging found
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