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The Amazing Aging Mind

Living with and learning from Alzheimer's, Parkinson's and other dementias

Water and The Aging Brain

by Marty D on Thursday, February 23rd 2012     7 Comments

water and brain function

Water and the Brain

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

 

 

 

 

 

 

Best of the Web Nomination

by Marty D on Thursday, February 23rd 2012     4 Comments


This site has been nominated as a Best of the Web in “Best Senior Living Blogs by Individuals 2012” category. If you agree, you can vote for me here!
Thank you!
Vielen dank!
Muito obrigada!
Arigato gozaimasu!

 

 

 

 

 

 

Bexarotene: Hope, Hype, Hooold It!

by Marty D on Monday, February 13th 2012     3 Comments

By now it’s not news that scientists at Case Western have successfully used a cancer drug to clear plaques from the brains of mice that were engineered to have Alzheimer’s, resulting in a reversal of rodent dementia. The hope is that this drug will do the same for humans.

Here is a more in-depth explanation of Bexarotene (“Drug Reverses Alzheimer’s Symptoms in Mice”):

Alzheimer’s disease arises in large part from the body’s inability to clear naturally-occurring amyloid beta from the brain.
In 2008, Case Western Reserve University researcher Gary Landreth, professor of neurosciences at School of Medicine, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. […] The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors, which control how much ApoE is produced. …bexarotene improved memory deficits and behaviour even as it also acted to reverse the pathology of Alzheimer’s disease [and] worked quickly to stimulate the removal of amyloid plaques from the brain.
[T]he drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice.

Here is my visual explanation gleaned from an article on curealz.org: …read more  

 

 

 

 

 

 

Guest Post: I Wish I Knew Then What I Know Now

by Marty D on Wednesday, January 25th 2012     7 Comments

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  

 

 

 

 

 

 

The Brain: Divided We Conquer

by Marty D on Monday, November 21st 2011     No Comment

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.

 

 

 

 

 

 

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Does the Pursuit of Happiness Lead to Brain Aging?

Pursuit of Happiness and Aging

Pursuit of Happiness and Aging

I was listening to Terry Gross interview David Linden on Fresh Air about his book The Compass of Pleasure, and something kept nagging at the back of my thinker throughout the interview. Something familiar. Something that seemed to connect with all the reading and writing I’ve done on Alzheimer’s and the brain this past year.

So I re-listened to the Fresh Air segment today, then did some quick digging through articles I’ve seen online on the brain, stirred it all around, let it simmer some more, and here is the reduction I got.

Maybe our addiction to the pursuit of happiness is contributing to brain aging. It’s not an umbrella cause, of course. You would never have been able to say that Mom led a hedonistic lifestyle. And Ronald Reagan pursued a lot more things than happiness. But still… The connection between what Dr. Linden was saying and what I’ve read makes me suspicious.

In David Linden’s Compass of Pleasure, he talks about the pleasure area of the brain as being that part that-in response to certain activities or substances-produces dopamine. Dopamine is the “feel good” neurotransmitter in the brain. It is activated when we engage in certain activities or thought processes, but it is also activated when we injest/inject food, alcohol, narcotics.

Some things that produce dopamine are completely healthy. Like a good run, the enjoyment of friends, reading a stimulating book.

Some things are borderline good. Like food. Everybody needs it. The pleasure of good food produces dopamine. But when pleasure is sought after for pleasure’s sake, “the brain’s dopaminergic circuitry gets blunted. In all cases of producing pleasure in the brain, it takes increasing levels [of a thing] to produce the same level of pleasure” (quoting Dr. L). So with food, you eventually get overweightness if the pleasure of food is pursued beyond the body’s need for it. Obesity is contributing to an epidemic of Diabetes, which is strongly linked to brain aging. By indirect means, then, the pursuit of a happy palate can lead to brain aging.

Then there are things that produce dopamine (or cause its production) that are not healthy. Like alcohol, nicotine, cocaine. This falls in with the acetaldehyde hypothesis I wrote about in Does Alzheimer’s Take Guts. Alcohol, cocaine, and especially cigarette smoke have-at some point in their metabolic breakdown-the toxic aldehyde acetaldehyde. Very destructive to the brain. Dopamine is produced as the end-process of breaking down harmful aldehydes into harmless acids. It’s the brain’s “Yahoo!” after saving the day from the bad guys. That “Yahoo!” may be a good thing, but again, in order to get it a second, third, and nth time, you have to increase the attack on the body. [Interestingly, Disulfiram‘s use to treat alcohol and cocaine addiction works by inhibiting ALDH2 (aldehyde dehydrogenase) which is the enzyme that metabolizes acetaldehyde. It lets the toxin do its full work rather than disabling it by metabolizing it into a harmless acid. So the brain does not get its “yahoo!” And if you get no yahoo, you don’t repeat the action.]

The problem with focusing on happiness above all else is that we may end up using the short-cut and more harmful methods of getting that dopamine high.

Dr. Linden’s solution? “Try to take your pleasures broadly: exercise, meditate, learn, have moderate consumption of alcohol, moderate consumption of food.”

I would add: pursue friendships, do charitable work, tend a garden, read a good book (get more ideas at Changing Aging).

As Captain Kirk once said, “There are a million things you can have and a million things you can’t have. Choose the million you can.”

See also:
Ethanol and acetaldehyde action on central dopamine systems: mechanisms, modulation, and relationship to stress.

Age-Dependent Neurodegeneration Accompanying Memory Loss in Transgenic Mice Defective in Mitochondrial Aldehyde Dehydrogenase 2 Activity

Mind Over Body in Parkinson’s Disease

Deep In The BrainDeep In The Brain is a cerebral self-examination written by a philosophy professor who was riding the top of a success wave when he was diagnosed with Parkinson’s. Talk about the relationship between mind and brain! Here is one who, thanks to his training, steps outside himself to make an objective assessment of his behavior even as he battles the attachment he has to that self.
In this book, Helmut Dubiel analyses his response to the personal and social implications of his Parkinson’s disease. He does not blame or excuse. Rather, he tries to put his and other’s reactions in context of the overarching laws of social interaction.
There is pain in this book. There are lies and pity and anger and judgment. But mostly, there is acceptance of the facts of disease and an acknowledgement of man’s irrepressible will to live and to thrive.

Yesterday as I read this book to Dad, I noticed him fidgeting more than usual. I stopped and asked him what was the matter. He said, “It seems like you’re reading about me.” I explained that this was a philosophy professor writing about himself. Dad calmed back down and listened with interest. Dad doesn’t talk about his inner battles much, so this would logically be painful for him. But good. I think this was one of Professor Dubiel’s hopes-that through his honest self-examination, others would feel released from the need to hide from their disease and, in so doing, find relief.

I’ve often asked people, “Which would you prefer: to lose your body or to lose your mind?” Given that I live with one parent with Alzheimer’s and the other with Parkinson’s, this question has personal weight. In his book, Professor Dubiel clearly expresses his preference for holding onto the self despite the ostracism brought on by the physical distortions of Parkinson’s. Knowing you are being unfairly rejected is still preferable to knowing nothing at all. On the other side, in Still Alice the protagonist affirms this appreciation for the self when-in a lucid moment-she acknowledges “I didn’t meant to get this way. I miss myself.” The mind is a far greater gift than the body.

Of course, in the end, Parkinson’s takes the mind as well.

My take-away? Pray for a cure for both diseases; forgive my and others’ shortcomings; enjoy today.

Citizen Science: Help Shed Light on the Brain-Gut Connection

brain in bulb

Citizen Science

At a time when Americans, along with citizens from many countries around the world, are increasingly disillusioned with the broken top-down model of leadership—be it in politics, economics, or science—it’s exciting to see opportunities popping up for bottom-up, citizen-driven models for change. Individuals are making things happen in politics (as in the Facebook-driven “Arab Spring” revolution); in economics (the Bill and Melinda Gates foundation; children helping children in the WE DAY movement, etc); and in science (Citizen Science Alliance, SciStarter, and even DIY blogs such as Instructables).
Read more

Alzheimers and Regression

altimersToday the world has been given the very bad news that there is nothing that can help prevent or slow the progression of Alzheimer’s. The disease is a thief and a murderer, and nothing can stand in its way.

I say the folks who did these studies need to study Mom. Round out the evidence of all that hopeless progression with a little taste of surprising regression.

I wrote the rest of this post a week ago, but only got around to publishing it today:

Good news!

Mom is going backwards. She’s regressing, it seems to us, and that’s a good thing when you have Alzheimer’s.

How? What? When? Where? Why? Is it wishful thinking that we’re seeing marked improvement in Mom’s cognition, or is this real?

Exactly what I’m asking myself these days. Granted, being a highly motivated observer may make my observations suspect, but I feel it would be irresponsible not to report what appears to be clear evidence of improvement in Mom’s condition. It would be irresponsible of you not to suspect my findings, but dumb not to take a look at all.

So here goes.

A few weeks ago, we who have been taking care of (or been around) Mom for the past three years noticed that we were telling people Mom was having a good month. We were used to telling people that Mom was “having a good day” every now and then. A good day once a week was a good thing. But the entire month of March of this year seemed to be “a good day.” It came to the point that we were scratching our heads saying, “Hmm. Maybe Mom doesn’t have Alzheimer’s. Maybe this was all stress, and now that she’s been de-stressed for three years, she’s coming back.”

Memory aid

Wall of memories

So I decided to take inventory of the new signs of cognition (and physical improvement) coming from Mom these days. What exactly is she doing that she wasn’t doing before? This is what I have:

  • Mom has gained weight. Exactly a year ago Mom weighed 85 pounds and was bed-ridden with pneumonia. Hospice pronounced her a week from the grave. Today Mom weighs 95.5 pounds. No sign of physical sickness (OK, an occasional night fever and drippy nose).
  • Mom sucks from a straw. For the longest time, we were having to “prime the pump” to get Mom to suck from a straw. A year ago, when we put a straw in her mouth, nothing would happen. So we’d plug the straw with our finger, then release the contents into her mouth, and, voila, she’d start sucking. Now Mom sucks as soon as the straw hits her lips.
  • Mom opens her mouth at the sight of food. Again, for the longest time we’d just get a pleasant stare when we lifted a fork to her mouth. Two years ago, it would take us a good hour and a half to get through breakfast because it was only one time out of ten that Mom’s lips would part when we brought food to her mouth. Now, six-seven times out of ten,  her mouth opens like a baby bird’s. Breakfast time has been cut in half.
  • Mom swallows. Up until (this is where I wish I’d kept an exact diary) about four months ago, Mom had a permanent sore on the right side of her mouth. This was caused by the fact that Mom leans to the right when she sleeps, and food that remained in her mouth (because she wasn’t aware enough to swallow) dribbled out and ate at her skin. No matter how well we brushed her teeth and how much Vaseline we slathered around her lips, the sore was there off and on for the last three years until-a few months ago. The sore has not returned.
  • Mom watches TV now. Meaning, she actually turns to it, focuses on it, and laughs on cue-sometimes for a 10-15 minute stretch. This hasn’t happened at all in the past three years until this “awakening.”
  • Mom stops at the photo gallery in the hallway, looks at individual family photos and “comments.” For the past three years we’ve been walking through the hallway with Mom-past a 4 foot x 4 foot photo gallery-occasionally stopping to show Mom the family photos in hopes of getting a response. She wouldn’t even look where we were pointing. And if she focused at all, it would just as likely be on a knot in the wood frame as on a photo. Now Mom takes the initiative to stop and look from frame to frame, pointing, jabbering, looking at us and back at the photos. Sometimes getting teary-eyed at our description of the photos.
  • Mom is using sentences. I wrote in a previous post that Mom’s language consists almost entirely of two syllable experiments in sound with an occasional word thrown in. We used to get so excited when she uttered a word that we’d call a family member and share the big news. In the past couple weeks, Mom has used short sentences. Like three days ago when I put her to bed, I said, “Mom, I love you.” She nodded and said, “For me, for me, for me too too.” The next morning at breakfast I tried to give her some juice while she was still chewing on her eggs and she shoved my hand aside and said “Put it down down.” I put her down for a nap in the afternoon, put on some Vivaldi, and did a farcical ballet dance (a la BodyVox). She nodded and said, “Yes. I do too too too.” Then that evening when I tried to give her her Seroquel (ground up in some juice), she shook her head. I kept bringing the juice to her mouth, and in exasperation she said, “Tsk! What what what do you do?” (Translation, “cut it out!”).

Four sentences in two days! Yesterday was a quiet day for Mom. No miraculous signs of anything. I’m dying to report more on this healing process, but Mom is not a science project, and I have to remember that she is worth all my love no matter what direction her mind and body take.

But I do think it’s worth mentioning that something has happened to Mom that has sent this Alzheimer’s into some sort of retreat. There is more than death taking place in her brain. Somewhere, somehow, regeneration is taking place as well.

Have any of you had the experience of watching a loved one with Alzheimer’s have a good month? I know Bob DeMarco recently reported an extraordinary event with his mother Dotty. Huge “regressive” step.

Next question will be, what could be causing these amazing regressions? We may have to rely on each other-the caregivers-to find the answer rather than on lab tests alone.

A Children’s Book about Aging?

Aging is fun

Aging is fun!

Yesterday I took Dad in to see a back specialist. She was to tell us whether or not Dad would be a good candidate for surgery for his spinal compression fracture.
It's just one doctor after another these days…
We barely got to the clinic and we were both already exhausted: Dad from getting dressed, fed, squeezed into a jacket, compressed into the car, ejected from the car, and hung in a wheelchair. Me from doing all that to him without the cooperation of his muscles. We didn’t even want to go into the clinic. I told Dad that what we should do is write a children's book about aging and how fun it is. Dad laughed. I said we could describe how you get to ride around in a cool scooter—even inside the house. And how you get to have cool leopard print all over your skin without paying a cent for it. And how if you get skin cancer on your ear, you have to have a chunk cut off (like Dad) and then you can fit right in with the folks at Rivendell or Lothlorien.
Big smile.
I really see some potential there.
Might as well take this big old lemon and make lemonade.
(P.S. If you have any more ideas for the book, let me know)

How Aricept Works: U.S. vs. U.K. Prescription Policy

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.
I’ll explain:
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.

Alzheimer’s and the Artistic Mind

Une Ombre au Tableau

Fleeting Memory

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.

Free Academy for The Aging Brain

sunflowers

Celebrate Your Age

A couple days ago we had a March Babies birthday party here at the house. It’s a tradition my sister started a few years ago because so many of her friends have birthdays in March, and this is a great way to kill a bunch of birds with one shotgun.

As I was sitting listening to our various conversations around the table, something struck me as different this year. We’re all hovering around 50—give or take a couple years—and the aging process is beginning to take a more prominent seat at the table. Not only do conversation topics start with the premise of aging: declining health, the cost of health insurance, etc, but it seems that no matter what the topic, it eventually touches on something to do with aging.
Read more

Paradigm Lost: Alzheimer’s, beta amyloid, fund-raising, and a taboo research topic?

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 in Alzheimer's pathology

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.

Alzheimer’s and the thrill of language

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…

The Brain’s Springboard to Creativity

the creative mind

The Creative Mind

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.
Read more

Caregiving and Music: Pandora to the Rescue

Caregiving and musicAfter 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:

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

Bexarotene: Hope, Hype, Hooold It!

By now it’s not news that scientists at Case Western have successfully used a cancer drug to clear plaques from the brains of mice that were engineered to have Alzheimer’s, resulting in a reversal of rodent dementia. The hope is that this drug will do the same for humans.

Here is a more in-depth explanation of Bexarotene (“Drug Reverses Alzheimer’s Symptoms in Mice”):

Alzheimer’s disease arises in large part from the body’s inability to clear naturally-occurring amyloid beta from the brain.
In 2008, Case Western Reserve University researcher Gary Landreth, professor of neurosciences at School of Medicine, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. […] The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors, which control how much ApoE is produced. …bexarotene improved memory deficits and behaviour even as it also acted to reverse the pathology of Alzheimer’s disease [and] worked quickly to stimulate the removal of amyloid plaques from the brain.
[T]he drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice.

Here is my visual explanation gleaned from an article on curealz.org:
Read more

The Aging Brain and the Flip Side of Aphasia

Yesterday I asked my sister—who is visiting from abroad—what signs of Alzheimer’s she sees in herself. She rattled off some memory problems such as forgetting names of acquaintances or not being able to place someone’s face when out of context. Nothing particularly Alzheimersy, just decreased mental sharpness.
She then asked me if I was experiencing any unusual mental hyperabilities and went on to explain how she seems to have gained a fantastic ability to call up words she didn’t even know she knew.
Funny, I told her. I had this post saved as a draft when she asked me the question. The answer is yes, I’m experiencing this very same thing, and am curious to know if there is a name for it.
Is there such a thing as hyperphasia—the flip side of aphasia? The term hyperphasia exists, and it’s defined as an uncontrolled impulse to talk. But that’s not what I’m referring to. I’m referring to the mind’s sudden ability to pull up obscure words when common words won’t present themselves. Words so obscure that we had no idea we knew them.
I’m well acquainted with aphasia—the “tip of the tongue but it just won’t come” nature of language loss. I’m also familiar with another embarrassing result of gradual mental decline: the mind’s tendency to call up words similar in shape, but wholly different in meaning from the one the user wants. Try Googling “fairy schedule” next time you want to cross the Puget Sound to see what I mean.
But what is it called when the mind calls up unknown words that perfectly fit the context they were intended for? Does neurology study mental surfeits as well as deficits?
The flip side of aphasiaI told my sister that I’ve had arguments in my head over this new ability. One night, for example, I went to bed, and as I lay my head on the pillow a picture of our living room doorway came to mind, and with it the word “transom.” I immediately questioned myself:
“Transom? What’s that?”
“It’s the big piece that spans the top of the doorway, dummy.”
“How’d you know that?”
“I don’t know. I just know that it is.”
“You’re probably thinking of Hansom. And I think that’s a horse carriage, not a doorway.”
“No, I know hansom is a carriage. Transom is the door thingy.”
With that, I got out of bed and looked the word up in the dictionary: a horizontal crossbar in a window, over a door, or between a door and a window or fanlight above it
“See?”
“OK, you were right.”
My sister laughed and said, yes, that’s exactly what goes through her brain.
So my question is, what is this newly acquired hyper-phasia called? And is it common to everyone as their minds begin to deteriorate?

The Truth About Alzheimer’s and Quality Time

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.

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