Before the Valley

In a talk a few years ago, Alan Lightman underscored an important commonality between science and literature: Both the scientist and the artist are seeking truth.

The tests of the scientist's invention are more definitive; no matter how beautiful a scientific theory is, it has a terrible vulnerability - it can be proven false. A writer's characters or story cannot be proven definitively wrong, but they can ring false and thus lose their power with the reader, and in this way, the novelist is constantly testing his fiction against the accumulated life experiences of his readers.

Today's exhibit that relates to Lightman's point? Alzheimer's.  Well, kind of about Lightman's point, as in the scientific and literary approaches to the disease that I have dreaded about ever since my thirties when I read Sherwin Nuland's How We Die.

Big news from the world of medicine regarding Alzheimer's:

The Food and Drug Administration on Monday approved the first new medication for Alzheimer’s disease in nearly two decades, a contentious decision, made despite opposition from the agency’s independent advisory committee and some Alzheimer’s experts who said there was not enough evidence that the drug can help patients.

The drug, aducanumab, which will go by the brand name Aduhelm, is a monthly intravenous infusion intended to slow cognitive decline in people with mild memory and thinking problems. It is the first approved treatment to attack the disease process of Alzheimer’s instead of just addressing dementia symptoms.

But, there is a reason why this is considered a contentious decision: "the amyloid hypothesis, which pinpoints clumps of the toxic protein as the root cause of cognitive impairment, has yet to be proven."  It reinforces Lightman's point that "no matter how beautiful a scientific theory is, it has a terrible vulnerability - it can be proven false."  

Meanwhile, last night I read this fantastic short story that is set in an old age home.  It is a social commentary on aging and dementia that is presented as fiction.  The truth in the novel is consistent with how I understand life.  It is true.  As Lightman said, we believe in the ending in good fiction:

[We] know that it's true even in fiction because it accords with our life experiences, with our understanding of human nature, and it causes us anguish. ... A writer's characters or story cannot be proven definitively wrong, but they can ring false and thus lose their power with the reader, and in this way, the novelist is constantly testing his fiction against the accumulated life experiences of his readers.

We will find out, sooner or later, whether the amyloid hypothesis and the treatment are proven false.  But, the fact remains that if we are lucky enough, we will become old, and some of us will slip into the netherworld of dementia. Novelist force us to think about that, even as scientists work hard to develop drugs to treat the problem.

We need the novelist and the scientist to help us out.

Memories!

"His father has Alzheimer's, and doesn't recognize his own son," she said.

Getting old is not for the faint-hearted!

Ever since I read Sherwin Nuland's How We Die, I have always worried about falling victim to Alzheimer's.  I keep reassuring myself that there has not been any case of dementia in the family, including the extended family.  But then I don't want to be the first either.

When I drafted a will more than two decades ago, my attorney laughed off this worry of mine.  Because, he said, I won't know anything as an Alzheimer's patient--the problem will be somebody else's.  But then, I don't want to become somebody else's burden.

"It is a bleak picture."

There is no known cure. Some medications can reduce memory loss and aid concentration, but these merely alleviate the symptoms or boost the performance of those neurons in the brain that remain unaffected. They do nothing to stop or slow down the killing-off of brain cells by this neurodegenerative condition.

Yes, there is a great deal of research being done to treat, if not cure, Alzheimer's.  But, ...

Especially for someone like me who believes that my memories are all that I will take with me, the loss of memories will be terrible. But, then is any ending any more pleasant than another, really!

Perhaps even my blogging is an extension of creating memories.  A modern day version of how through the ages we humans have told each other stories enough and more times. Most of the old stories that we talk about are heartwarming. But then there are those that make us dwell on the unpleasant tastes that life leaves on our tongues.

I remember coming across a wonderful line by Haruki Murakami:

Memories warm you up from the inside. But they also tear you apart.

May you create your memories that will warm you from the inside, about which you can then talk and blog about--and keep Alzheimer's away, forever.

When adults go commando ...

The end of August leading up to Labor Day is traditionally slow news time here in America.  Even C-Span has to resort to reruns!

(I know what you are thinking: Don't I have better things to do than watch C-Span? You don't know what you are missing out on, dear reader!)

A senator--of course, an old, white, male--was introducing Seth Rogen.
Yes, that Seth Rogen.
At the US Senate!

He had his glasses on--the typical celebrity approach to coming across as serious and intellectual and ready to utter something moving and profound.  These movie people literally live up to "all the world's a stage."

I decided to watch anyway.

One of the best things I could have done.  In fact, I would recommend that you, too, watch it.

Seth Rogen told a wonderfully warm story about a horrible aspect of life--his mother-in-law was diagnosed with early onset of Alzheimer's when she was only 54.  Fifty-four!  It has been downhill since then for her.  Unlike other top ten reasons for death, Rogen noted, "there is no way to prevent, cure, or even slow the progression of Alzheimer's Disease."  He commented about how it was way more expensive than treatment for heart conditions, which are expensive to begin with.

I suppose this discussion continues, in a way, from where the ALS Ice-Bucket-Challenge post ended.  But then, as my links to posts from the past show, the conversations on any of the topics have not ended, have they?  Nor is this the first time that I have something to say about Alzheimer's and dementia.

Alzheimer's is one awful disease.
For the patient.
For the family and friend.
And, yes, for the bank balance too.

In 2012, one out of every eight people aged 65 and older in the U.S. – more than 5 million – had Alzheimer’s, and payments for health care, long-term care, and hospice services were estimated to be $200 billion (not including the work of unpaid caregivers).
By 2050, barring the development of medical breakthroughs to prevent or more effectively treat the disease, the number of Americans with Alzheimer’s may triple to 16 million, with annual costs of care projected to reach $1 trillion. Without disease-modifying treatments, the cumulative costs of care for people with Alzheimer’s from 2010 to 2050 will exceed $20 trillion, in today’s dollars.

The article notes that this is a projection and it does not mean that we should start setting aside twenty trillion dollars.  Instead, and wisely, the author compares it with the case of polio:

From 1940 to the mid-1950s, polio struck 400,000 American children and millions more worldwide. The epidemic peaked in the early 1950s with 58,000 new cases in 1952 and another 35,000 in 1953. But, thanks to the Salk polio vaccine, by 1957, new polio cases had been cut by 90 percent, and by 1960 the disease was almost entirely eradicated in the United States.
Michael Milken has pointed out that, in the early 1950s, the cost of polio care in the U.S. was predicted to be $100 billion by the year 2000 – back when a billion dollars was a lot! In fact, he says, “today’s polio immunization programs cost one thousand times less than that and have virtually eliminated the disease.”

Yes, it will require many more Salks.

NPR reported that one group that is helping us with the research for treatment of this awful disease is people with Down Syndrome.

Down syndrome is a genetic disorder that's best known for causing intellectual disability. But it also causes Alzheimer's. "By the age of 40, 100 percent of all individuals with Down syndrome have the pathology of Alzheimer's in their brain," [Michael Rafii director of the Memory Disorders Clinic at UCSD] says.

A depressing post on a warm summer night, yes.  But, life is not all fun all the time--even Seth Rogen knows that.

Why do we humans live so long? And, oh, the problems at old age!

From our own lives, from the stories of our own families, and from scientists, we know all too well that we humans are living longer and longer and longer.  This Scientific American piece explores why we live such long lives:

Most researchers chalk up our supersized life span to the advent of vaccines, antibiotics and other medical advances, the development of efficient urban sanitation systems, and the availability of fresh, nutritious vegetables and fruit year-round. Indeed, much demographic evidence shows that these factors greatly extended human life over the past 200 years. But critical as they were to extending human life, they are only part of the longevity puzzle, Finch warrants. Marshaling data from fields as diverse as physical anthropology, primatology, genetics and medicine, he now proposes a controversial new hypothesis: that the trend toward slower aging and longer lives began much, much earlier, as our human ancestors evolved an increasingly powerful defense system to fight off the many pathogens and irritants in ancient environments. 

We need to keep in mind that our lifespan even now is supersized:

Our kind is remarkably long-lived compared with other primates. Our nearest surviving relatives, the chimpanzees, have a life expectancy at birth of about 13 years. In contrast, babies born in the U.S. in 2009 possessed a life expectancy at birth of 78.5 years. 

Of course, those who do not believe that the chimpanzees are our relatives won't bother with such scientific inquiry anyway!

Apparently it could come down to one "apolipoprotein E (APOE) gene":

APOE e4's DNA sequences closely resemble those in chimpanzee APOE, strongly suggesting that it is the ancestral human variant that emerged near the beginning of the Homo genus more than two million years ago and thus may have had the earliest effect on our longevity. Differing in several critical amino acids from the chimp version, APOE e4 vigorously ramps up the acute phase of inflammation. It boosts the production of proteins such as interleukin-6, which helps to increase body temperature, and tumor necrosis factor–alpha, which induces fever and inhibits viruses from replicating. Equipped with this supercharged defense system, children in ancient human families had a better chance of fighting off harmful microbes that they unwittingly ingested in food and encountered in their surroundings. “When humans left the canopy and went out onto the savanna,” Finch notes, “they had a much higher exposure to infectious stimuli. The savanna is knee-deep in herbivore dung, and humans were out there in bare feet.”
Moreover, early humans who carried APOE e4 most likely profited in another key way. This variant facilitates both the intestinal absorption of lipids and the efficient storage of fat in body tissue. During times when game was scarce and hunting poor, early APOE e4 carriers could draw on this banked fat, upping the odds of their survival.
Even today children who carry APOE e4 enjoy an advantage over those who do not. In one study of youngsters from impoverished families living in a Brazilian shantytown, APOE e4 carriers succumbed to fewer bouts of diarrheal disease brought on by Escherichia coli or Giardia infections than noncarriers did. And they scored higher on cognitive tests, most likely as a result of their greater absorption of cholesterol—a dietary requirement for neurons to develop in the brain

How does this all lead up to the old age problems that the blog post title drew you in?  Blame it on the same apolipoprotein E (APOE) gene!

APOE e4 carriers, with their enhanced immune systems, tended to survive many childhood infections. But they experienced decades' worth of chronic high levels of inflammation in the pathogen-rich environment—levels that are now linked to several deadly diseases of old age, including atherosclerosis and Alzheimer's. ...“And while it might be pushing it to say the senile plaques of Alzheimer's are some form of scab, like the plaques on artery vessels, they have many of the same components,” Finch suggests.

The apolipoprotein E (APOE) gene might turn out to have been one heck of a Faustian bargain we made with evolution!

One of the awful downsides to this long life is Alzheimer's.  (Yes, an issue that I have blogged about before, like here and here.)

As lifespans increase, we can expect more of us to be afflicted with this awful disease:

More than 35 million people worldwide live with dementia today, according to a new report. By 2050, that number is expected to more than triple to 115 million. The majority require constant care; they're dependent -- and that dependence can impact their loved ones in unmeasurable ways.

You might think that 115 million in a population of nine billion wouldn't matter much.  But, it will.

the problem is getting worse. Increasing life expectancies and an aging population are creating a group of seniors that's bigger than the working-age population that supports them, the report says. Approximately 4% of the population in developed countries now is currently over the age of 80; in 2050, experts predict, that number will rise to 10%. ...
People with Alzheimer's live on average four to eight years after they're diagnosed, but some may live 20 years beyond their initial diagnosis.

So, hey, here is the bottom-line: Enjoy the good life and be thankful for it.  You never know how things might be when you reach 75.

And treat our chimp relatives well!

It is dementia and Alzheimer's everywhere I look :(

It surely cannot be a case of we only see what we want to see.  It is not that I am scanning the vast ocean of words only to pick out articles on dementia and Alzheimer's.  Heck, even when I am quietly sitting by the river, a stranger ends up talking with me about the death of her mother who spent her final few months at an Alzheimer's care facility!

Last night, my bedtime reading was the latest issue of the New Yorker.  I had already flipped through the cartoons earlier in the day.  Even that was a bummer--such blah cartoons!

Like a moth attracted to a light, I went after Patricia Marx's essay (sub. reqd.) on this topic, where she notes:

by the advanced age of twenty there is a very good chance that our prefrontal cortex (the brains of the brain, responsible for problem-solving, decision-making, and complex thought) has already begun to shrink. We humans, by the way, are the only animals whose brains are known to atrophy as we grow older, and—yay, us again—we are also sui generis in suffering from Alzheimer’s disease. As distinctions go, this may not be as auspicious as, say, the opposable thumb.

I tell ya, it was such a relief (!) to read late at night that I have been on a downward trend ever since I came to the US.  This is making real my joke that by coming to the US, I simultaneously lowered the IQ in both the countries!

A few days ago, I told a friend that I intentionally go to a new grocery store every once in a while, even if it is only to get the usual stuff.  To create new pathways in the brain.  When driving around town, or to work, I venture off course partly for the same reason--to keep my brain active.  New recipes. New music. New stuff within my liking.  All to make sure that I can at least delay the onset of that disease I dread so much.  Apparently, I am not a lonely worrywart:

A 2011 survey found that baby boomers were more afraid of losing their memory than of death.

Well, technically I am not in the boomer generation!  But, the worry is for real!

We do all these because as of now, we are clueless otherwise.  We have progressed one step though--we have reached an understanding that "Alzheimer's and other dementias" are diseases, "rather than as a consequence of normal aging."  Which is why not every single who gets old has dementia.  All we know is that something happens with the cranial biochemistry.

People with more concerns about memory and organizing ability were more likely to have amyloid, a key Alzheimer's-related protein in their brains.

That is the only good news.  The bad news is that we don't have a clue on what to do about it. Not yet, anyway.

Maybe the New Yorker should go easy on this topic.  I mean, feature such topics not this often, every month!  And that too in the summer, when we expect lfe to be fun, fun, and more fun!

I am not the only one who worries about forgetting!

I wonder why I am on this theme.

What was I saying?

Ah, yes, I wonder why I am on this theme.

What was I saying? ;)

Forgetfulness - Billy Collins

The name of the author is the first to go
followed obediently by the title, the plot,
the heartbreaking conclusion, the entire novel
which suddenly becomes one you have never read,
never even heard of,

as if, one by one, the memories you used to harbor
decided to retire to the southern hemisphere of the brain,
to a little fishing village where there are no phones.

Long ago you kissed the names of the nine Muses goodbye
and watched the quadratic equation pack its bag,
and even now as you memorize the order of the planets,

something else is slipping away, a state flower perhaps,
the address of an uncle, the capital of Paraguay.

Whatever it is you are struggling to remember,
it is not poised on the tip of your tongue,
not even lurking in some obscure corner of your spleen.

It has floated away down a dark mythological river
whose name begins with an L as far as you can recall,
well on your own way to oblivion where you will join those
who have even forgotten how to swim and how to ride a bicycle.

No wonder you rise in the middle of the night
to look up the date of a famous battle in a book on war.
No wonder the moon in the window seems to have drifted
out of a love poem that you used to know by heart.

Forget-me-not

From Costa Rica to ... Dementia

Roberto was a funny guy.  During one conversation, he said, "oh, wait, what is the name of that German guy? A big time doctor?"  After a momentary pause, he resumed, "Oh, yes, Alzheimer."

We laughed.  Hey, I like a good joke.

The vacation is over, and Costa Rica seems more and more distant in the rear view mirror.  As I returned to my regular reads, it turns out that two of my favorite publications had something significant to offer me about Alzheimer's.

This article (sub. reqd.) in the New Yorker notes:

In the United States alone, roughly five million people suffer from Alzheimer’s, a figure that is expected to more than double by 2050. The annual cost to the nation for treating the disease may then approach a trillion dollars; the cost in suffering is incalculable.
Yet three decades of Alzheimer’s research has done little to change the course of the disease.

Way back, when I was barely thirty years old, I decided that I ought to make clear to wife and daughter my preferences for medical treatment.  I didn't want any big time life supporting machines to be hooked up to me.  Donate my body to a medical school. At a dinner table conversation, I told the attorney friend that my greatest worry was that I would end up with dementia. With Alzheimer's.

Dennis laughed.  "Alzheimer's won't be your problem at all, but somebody else's."  And he looked at my daughter.

As one who loves living the life of the mind, and with thinking as my profession and hobby, I shudder to think that I could lose it and then be in a state of being around without actually being around.  I have been waiting for some kind of a development that would nuke Alzheimer's before it actually begins.  A preemptive strike.  It is all the more important for societies all across the world to understand, and not merely because Sriram is worried about it, because of our longer and longer lifespans.

Current surveys show that, of the population over eighty-five, roughly a third of people worldwide have Alzheimer's. ... "If we lived long enough, would we all become demented, with plaques and tangles?  Is Alzheimer's just another name for aging?"

Doesn't take much to imagine the complexity involved.  Taking care of an Alzheimer's patient is no easy task for a caregiver.  If one decides to outsource this care-giving, the expense quickly adds up.

A recent study in the New England Journal of Medicine estimated that caring for an Alzheimer's patient costs forty-one thousand to fifty-six thousand dollars a year.

This piece in the Economist, also on Alzheimer's, puts the cost figures thus:

In America in 2010, the cost of treating those with dementia was $109 billion. That exceeds the cost of treating those with heart disease or with cancer. The RAND Corporation, a Californian think-tank, reckons this cost will more than double by 2040.

That comes across as a low estimate, compared with what the New Yorker suggests: "more than a trillion dollars a year by 2050."

Let's hope that the drugs that are in the trial stages will work out.

Here is to hoping that my constant worries will help in preemptive strikes against those crazy proteins that trigger the Alzheimer's.  If not, my daughter needs to be warned that Oregon's Death with Dignity won't extend to Alzheimer's patients--how can it when they cannot rationally think and decide for themselves!