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!

Back to the mind-over-brain thing in Alzheimer’s treatment.
I saw an old friend yesterday and we caught each other up on our families. I told him I recently lost my brother-in-law to brain cancer. He said he was about to lose his sister to the same. Then he shared how his sister—who has a month or two left to live and is tired as can be—blurted out a couple days ago that “There are just so many fun things left to do.” No self-pity; no giving up despite the shortness of time. Her mind is winning over her dying brain.
I am deeply humbled by this woman’s attitude. I want to think like her—to take what’s left in the glass and drink it! Yet here I am with probably years left to live, claiming to be getting the upper hand on this Alzheimer’s caregiving business, but feeling devoid of creative ideas for living, for laughing, for loving.

I need help making a list. I have to have a bunch of small stuff, because the big stuff like going to a play or out to dinner or hang gliding don’t work with both parents. I just want some ideas for bringing laughter into our home.

To start, here are some little things that make Mom laugh:

Dancing for her with a feather boa.
Episodes of “I Love Lucy.”
Singing raucous songs loudly.
Pretending to eat her up.
Laughing babies (like this youtube one):

Here are some things that make Dad laugh:

Pretending to eat him up.
Episodes of The Colbert Report.
Mom when she’s in a funny mood.
Exaggeration.

And here are some new things I’m going to try:

Wear a fake mustache to the dinner table.
Spray whipped cream on Dad’s nose.
Put a fake snake or tarantula in the bathroom before Dad goes in.
Find a DVD of Victor Borge (like this youtube):

I’d love to hear your ideas, and I’ll leave you with this fun project: make a muppet like the one in the introductory picture above to add some fun to your Alzheimer’s caregiving.
Wait, here’s another idea: make these funky glasses. They crack everybody up!

The other night I watched the movie Limitless. I thought it was a typical heart-pounding thriller with a touch of fantasy—in this case about a guy who discovers a drug that turns him into a genius. I thought the plot was moving toward the inevitable crash he would suffer when his supply ran out (as happened to everyone else in the movie whose supply ran out).
Then came the twist at the very end that made me laugh out loud. OMG, what Pretty Woman was to prostitutes, Limitless is to drug addicts and the whole drug industry.
If you’re smart enough, it says, you can make the perfect brain drug; you can take the last dose of the perfect drug to a lab and figure out how to reverse engineer and reproduce it; and you can figure out how to tweak it downwards in a perfectly safe manner (all within very short time periods); then you can wean yourself from a phenomenally addictive drug; and finally, you can train your brain to retain all the benefits of said drug once you have weaned yourself off it.
HA HA HA HA HA.

I think the whole problem I have with the drug industry is that, except in this extreme pharmacofantasy, it is additive rather than subtractive. You add one drug to treat a condition, then you add another to deal with the side effects of the first drug, then you add an nth drug to deal with the side effects of the combination of all the previous drugs.
Why not start with subtraction?
What are we injesting that we should cut out? Sugar? Preservatives? Smoke? Alcohol? Pesticides?
How often/much are we eating that we should cut back? Are we inhibiting certain enzymes—such as the anti-aging SIRT1—that only activate during fasting hours?
Maybe less is more?
Let’s start by removing the offending substances first, because once you start adding, it’s not you who benefit. It’s the industry that initially did have your brain in mind but now needs you to need them more and more.

Here’s a fascinating animation superimposed over a lecture by psychiatrist and writer Iain McGilchrist on the two hemispheres of the brain. You may have to watch it 15 times to really get it.

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.

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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e all know, even without reading research papers, that music has emotional benefit: it can excite and calm and induce a wonderfully cathartic weeping session. This applies whether you’re healthy or sick; whether you have Parkinson’s or autism or Alzheimer’s.

But studies have found that music can also be of cognitive benefit: it helps people remember things better.

What exactly does this mean, and what specifically does it mean for an Alzheimer’s patient? Does it mean that if you play the oldies station in the background all the time, your Mom will wake up one day and remember everything again?

Let’s look at the evidence:

First of all, "music" is a pretty general term. Are we talking about singing? Playing a guitar? Listening to Mozart? Listening to Bobby McFerrin’s improvisational jazz? Believe it or not, these are all different things.

According to a study reported by Time Magazine,("Music on the Brain")

Different networks of neurons are activated [in the brain], depending on whether a person is listening to music or playing an instrument, and whether or not the music involves lyrics.

In another study, quoted in Neuroscience for Kids,

researchers have recorded neuronal activity from the temporal lobe of patients undergoing brain surgery for epilepsy. During this study, awake patients heard either a song by Mozart, a folk song or the theme from "Miami Vice". These different kinds of music had different effects on the neurons in the temporal lobe.

Also, from Time'“Music on the Brain”

Experimental Audiology in Germany has shown that intensive practice of an instrument leads to discernible enlargement of parts of the cerebral cortex, the layer of gray matter most closely associated with higher brain function.

As you can see, different music affects different parts of the normal brain in different ways.

People are always studying the music-brain connection, trying to understand the mystery of it. There was a particular study done in 1993 that tried to see if music affected memory. The researchers used a song by Mozart for their experiment, and their results seemed to show that this composer’s music improved test-taking. This became widely known as The Mozart Effect, and people started playing Mozart to their unborn babies thinking it would give them a head start in learning.

Though later studies failed to duplicate the Mozart Effect (perhaps the only real effect is that Mozart helps relax the body right before a test), that original research sparked further research into music-as-memory-aid. A recent study, for example, found that Alzheimer’s patients can remember new information if it is sung to them much better than if it is spoken (as opposed to healthy people who can remember it equally well when sung as opposed to spoken).

We also know without reading studies that music helps trigger old memories. For example, when I hear the song "Dust in the Wind," I am immediately transported back to our family van as we drove across the country in 1977. I remember my oldest sister introducing this song to me, and how it resonated with the angst of my teenage years, etc. A whole cascade of memories brought on by a single song.

In a study reported by the Telegraph in 2009, researchers found that this recall effect is due to the fact that music is processed in the same area of the brain that forms vivid memories. They furthermore found that such memories appear to be immune to the ravages of Alzheimer’s. And this could lead to a unique kind of therapy:

Because memory for autobiographically important music seems to be spared in people with Alzheimer’s disease, …making a "soundtrack of someone’s life" before their mind is too damaged, and playing it back to them could help form a resistance to the disease.

Love the idea! Plus I have a variation on this idea from watching this next video of Bobby McFerrin (at a conference called "Notes and Neurons"), and from observing Mom as I play the piano. First, here’s Bobby:

What Bobby is doing here is getting the mind to go in a familiar direction (the pentatonic scale), then leaving an auditory blank and letting the mind fill it in. I mean, aside from jumping around, that's what he's doing. He’s giving the mind a puzzle to solve. He’s making the mind work. And working the mind is better than not working the mind if you want to keep it.

The next part of my idea came from playing the piano for Mom and watching her reaction. You should know Mom hasn’t spoken but a few words in a couple years, and she no longer sings intelligible tunes. You should also know that I don't play the piano. I used to when I was seven, but now my playing is reduced to guessing the notes with my right hand. I can play fast enough for the tune to be recognizable. Barely. Fortunately for Mom, the tune is always a hymn—something she is very familiar with. Unfortunately for Mom, I mangle the tune. And that's where the puzzle comes in.

See, when my finger's can't find the right note, Mom gets exasperated and sings it out loud to help me find the dang thing. I'm even wondering if this puzzle-solving exercise is a factor in Mom's recent awakening.

So here is my variation on the soundtrack idea. Try this exercise (for an Alzheimer’s patient) with the following video clip:

Play it once. It will probably be familiar to the listener already, but there are enough repetitions in this piece that parts of it will quickly become familiar if they aren’t already. Play the video again, but pause the video every so often. There are a ton of repeated theme snippets. Pause before a theme is repeated and see if the listener is prompted to supply the missing piece. If they do, you've got a good puzzle to use.

Then, if you do this with that "Life Playlist", you should be able to double the benefit in fighting that Alzheimer’s monster.

Related Posts:
Music and Caregiving—Pandora to the Rescue
Alzheimer’s and Music: Stimulating the Brain into Action
Related articles:
Posit Science Blog, Your Brain on Jazz
American Music Conference, Music and the Brain

The following describes the knowledge gained by Sharlene in the course of caring for both her parents with Alzheimer’s. It is not necessarily a reflection of my views, but I thought it good to publish the research of someone who has an insider’s view of Alzheimer’s dementia.

Sharlene Spalding is a naturopathic consultant in the village of Casco, ME. She is a former primary caregiver for two parents with AD. She holds a master’s degree in natural wellness. Sharlene is an excellent resource in natural healing and a hound dog when it comes to research. Because of what she knows now, she is committed to a pharmaceutical-free home that revolves around organic foods and herbs. You can visit her website at The Village Naturopath.
Read more

Now that’s what I mean. You read something about Alzheimer’s, and all of a sudden you see evidence everywhere that you’ve got it and that your life is over.
I’ve avoided reading Still Alice for years precisely because I knew it would send me reeling with the truth of my own “probable” early-onset Alzheimer’s. But I did finally pick it up, and, sure enough, suffered a major breakdown right about chapter three. Yikes! I do have it. Just like Alice, I forgot I was supposed to work on Friday, and when my sister called to remind me, I crumbled. It’s not just that I forgot. It’s that I forgot and didn’t have that nagging feeling telling me that I was forgetting something eating away at me. It was the peaceful forgetting that terrified me. Surely this doesn’t happen to a person unless they have Alzheimer’s. Ever. Right?

Is this forgetting normal or something more sinister? Is it stress from caring for Mom with Alzheimer’s and Dad with Parkinson’s (with a touch of menopause for me), or am I following in my mother’s footsteps?

The lucky thing for me is that I don’t have medical insurance-which means I can’t go to a doctor for a diagnosis. I say I’m lucky because, as we all know, it’s not so much the disease that hurts people, it’s the diagnosis. And it’s not just any diagnosis. Cancer, people rally around you. Alzheimer’s or any kind of mental illness, and the room empties out.
Shoot, you can have the disease for years, but as soon as you get diagnosed, that’s when the tazing starts. People just automatically take out their stigma-tazers and start shooting. And they think they have it set on stun, but really those stigma-tazers are always set on kill.

So my question is, what do you do when you read or hear about terrifying conditions to keep yourself from assuming yourself into that condition and absorbing the fear that is often marketed with it? How do you “keep your head, when all about are losing theirs”? (Kippling)
And once you’re diagnosed, how do you overcome all that tazing?
Chuck’s blog on early onset Alzheimer’s is, I think, a courageous way of dealing with one such diagnosis.
What is your way of dealing with the fear of Alzheimer’s-whether it’s diagnosed or imagined?

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 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“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.

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!

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

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.

Say, what?

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.

RELATED POSTS:

Alzheimer’s and Glucose Metabolism: the Niacinamide Experiment Part 1

Does Alzheimer’s Take Guts? The Niacinamide Experiment Part 2

Does Alzheimer’s Take Guts? (Continuation)

If you’re like me and need a visual representation of the brain’s anatomy to understand Alzheimer’s and Parkinson’s research better, here are a few good slide shows and videos for your educational pleasure:

How The Brain Works
From the Mayo Clinic. This is a good starter slide show of the brain’s main functions. In eight slides you get a basic outline of the lobes of the brain and their purposes.

Dementia Pictures Slideshow: Disorders of the Brain
From MedicineNet. These 31 slides show what happens to the brain in cortical, subcortical, progressive, primary, and secondary dementias.

Brain Tour
From the Alzheimer’s Association. In 17 slides you will learn about the brain’s basic functions, then how the brain is affected in Alzheimer’s by amyloid beta plaques and tau tangles.

Zoom In and Search for a Cure
From Emergent Universe. This is a fun, artsy, and very interactive show depicting what happens in the brain affected by Alzheimer’s Disease. Among other things, you will discover why ab42 is more toxic than ab40.

Inside the Brain: Unraveling the Mystery of Alzheimer’s Disease
This is a video put out by several government organizations (the NIH, NIA…) showing the pathology of Alzheimer’s in the brain.

The Secret Life of the Brain
From PBS. Here are three interactive shows (requires Shockwave), including, History of the Brain, 3-D Brain Anatomy, Mind Illusions, and Scanning the Brain.

Brain Rules: Sleep
Now that findings show beta amyloid buildup is cleared during sleep, this slide show will be of special interest, as it shows the role of sleep in brain function.