Roots of the irrational in American politics: pre-dementia and religion

I've written recently about the role of religion in the reasoning of the GOP base. This is an elephant in the room; pundits will discuss the role of American's exceptional fundamentalism in the context of abortion politics, but not in the context of debt politics. The mainstream media is missing an important ingredient in our political paralysis.

There's another elephant out there, and it will grow over the next ten years. The average American voter will become increasingly demented. Demented people rarely vote of course, but most dementia is the end stage of a very long process. Before a voter is disabled, they will lose the ability to process information, recall all but the most recent events, and adjust their beliefs based on evidence. They will, in other words, become less rational.

How big a factor is this?

We can make some estimates by starting with the end-stage state of clinical demential ...

Prevalence of Dementia in the United States: The Aging, Demographics, and Memory Study

... The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71–79 years to 37.4% of those aged 90 and older...

... The elderly population (those aged 65 years or older) in the USA is expected to double from approximately 35 million today to more than 70 million by 2030...

Of course these numbers are only a start. What we really want are numbers expressed in percentages of voters, and we want the average disease duration from judgment impairment to disability. Personally I suspect that's about 20 years, but the best data I could find was on a relatively rare and aggressive form of early dementia ...

Pre-dementia clinical stages in presenilin 1 E280A... [Lancet Neurol. 2011] - PubMed result

... Pre-dementia cognitive impairment was defined by a score 2 SD away from normal values in objective cognitive tests, and was subdivided as follows: asymptomatic pre-MCI was defined by an absence of memory complaints and no effect on activities of daily living; symptomatic pre-MCI was defined by a score on the subjective memory complaints checklist higher than the mean and no effect on activities of daily living; and MCI was defined by a score on the subjective memory complaints checklist higher than the mean, with no effect on basic activities of daily living and little or no effect on complex daily activities. De

... Median age at onset was 35 years (95% CI 30-36) for asymptomatic pre-MCI, 38 years (37-40) for symptomatic pre-MCI, 44 years (43-45) for MCI, and 49 years (49-50) for dementia. The median age at death was 59 years (95% CI 58-61). The median time of progression from asymptomatic to symptomatic pre-MCI was 4 years (95% CI 2-8), from symptomatic pre-MCI to MCI was 6 years (4-7), from MCI to dementia was 5 years (4-6), and from dementia to death was 10 years (9-12). The cognitive profile was predominantly amnestic and was associated with multiple domains. Affected domains showed variability in initial stages, with some transient recovery in symptomatic pre-MCI followed by continuous decline.

In this disorder asymptomatic pre-MCI started at age 35, and disability (dementia) at age 50. So the aggressive form has a 15 year course. I would expect less aggressive forms have a longer course, so I'll go with 20 years.

So by these very rough guesstimates about 15% of 50 year old voters will be impacted by "asymptomatic pre-MCI", an early form of cognitive disorder that will impact their judgment. That prevalence will go up with age. Since GOP voters are much older than Dem voters, this, like religious fundamentalism, will be concentrated in the GOP base and it will strongly impact GOP politics.

If you don't understand the two factors of religious fundamentalism and pre-dementia cognitive impairment you will have a hard time understanding the future of the GOP.

Dementia is normal - and what that means

In a post-industrial age of low birth rates the greatest economic challenge for wealthy nations is acquired cognitive disability -- better known as dementia.

So we ought to think clearly about dementia. It doesn't help that my generation of physicians were taught to think of dementia as an "abnormal" disease like the flu, rather than an all-but-inevitable consequence of aging.

A recent popular review, which was ironically intended to be inspiring, underscores how "normal" (typical) dementia is (emphases mine) ...

BRAIN POWER: At the Bridge Table, Clues to a Lucid Old Age

By BENEDICT CAREY

... In recent years scientists have become intensely interested in what could be called a super memory club — the fewer than one in 200 of us who ... have lived past 90 without a trace of dementia....

... Laguna Woods, a sprawling retirement community of 20,000 south of Los Angeles, is at the center of the world’s largest decades-long study of health and mental acuity in the elderly. Begun by University of Southern California researchers in 1981 and called the 90+ Study, it has included more than 14,000 people aged 65 and older, and more than 1,000 aged 90 or older.

... researchers have also demonstrated that the percentage of people with dementia after 90 does not plateau or taper off, as some experts had suspected. It continues to increase, so that for the one in 600 people who make it to 95, nearly 40 percent of the men and 60 percent of the women qualify for a diagnosis of dementia.

... it is precisely that ability to form new memories of the day, the present, that usually goes first in dementia cases, studies in Laguna Woods and elsewhere have found.

The very old who live among their peers know this intimately, and have developed their own expertise, their own laboratory. They diagnose each other, based on careful observation....

...Here at Laguna Woods, many residents make such delicate calculations in one place: the bridge table.

Contract bridge requires a strong memory. It involves four players, paired off, and each player must read his or her partner’s strategy by closely following what is played. Good players remember every card played and its significance for the team. Forget a card, or fall behind, and it can cost the team — and the social connection — dearly.

“When a partner starts to slip, you can’t trust them,” said Julie Davis, 89, a regular player living in Laguna Woods. “That’s what it comes down to. It’s terrible to say it that way, and worse to watch it happen. But other players get very annoyed. You can’t help yourself.”

... Later, the partner stares uncertainly at the cards on the table. “Is that ——”

“We played that trick already,” Ms. Cummins says. “You’re a trick behind.”

Most regular players at Laguna Woods know of at least one player who, embarrassed by lapses, bowed out of the regular game. “A friend of mine, a very good player, when she thought she couldn’t keep up, she automatically dropped out,” Ms. Cummins said. “That’s usually what happens.”

Yet it is part of the tragedy of dementia that, in many cases, the condition quickly robs people of self-awareness. They will not voluntarily abandon the one thing that, perhaps more than any other, defines their daily existence...

... In studies of the very old, researchers in California, New York, Boston and elsewhere have found clues to that good fortune. For instance, Dr. Kawas’s group has found that some people who are lucid until the end of a very long life have brains that appear riddled with Alzheimer’s disease. In a study released last month, the researchers report that many of them carry a gene variant called APOE2, which may help them maintain mental sharpness.

Dr. Nir Barzilai of the Albert Einstein College of Medicine has found that lucid Ashkenazi Jewish centenarians are three times more likely to carry a gene called CETP, which appears to increase the size and amount of so-called good cholesterol particles, than peers who succumbed to dementia...

Imagine how hellish that bridge table can be. Every game, a test. Show weakness, slip, and death is your fate. First social death, then the grave. It makes professional baseball look like ... child's play.

I'd bet a good amount that the "protective" "social" effect of playing bridge is bull poop. This is all about a survivor-effect correlation. Only the genetically gifted slow agers can play. On the other hand, I doubt that even the best of those bridge players could handle a modern knowledge worker job -- they are good for their age, but they are not immortal.

So if we (mostly) set aside wistful hopes of some kind of mental activity that protects against normal, all-but-inevitable, age related dementia, what do we have left to learn from these and similar studies?

We know it helps to be born clever, but that only gives your airplane more fuel -- it doesn't by itself slow the normal process of brain mush. Many brilliant thinkers with, at their peak, one in a million minds, are relatively disabled by their 70s - though still better off than most of us.

We can't do much with the brains we're born with, but we do have animal model evidence, and less definitive human evidence (because we don't randomly experiment then autopsy humans), that physical exercise is protective against normal dementia. Seems bizarre to me, but it holds up. On the other hand, head injury accelerates dementia, so don't make your exercise football, contact hockey, boxing, or horse jumping.

Exercise and head whacks aside, this is all about genes and medicines. It's about identifying those whose brains hold up longer, then figuring out the trick of it, then looking for a medicine that will help the average person. It's slow, hard work, but success is worth trillions in economic growth and a significant reduction in human suffering. By that metric, we're grossly underfunding this research. The potential payoff is enormous compared to say, cancer research. (I've been pointing this out, incidentally, for at least twenty years. It's not hard to do the math.)

Barring any breakthroughs, however, we boomers need to get real about our future. We expect we're going to have to keep working to 70 or beyond, but you can't cheat mother nature. Dementia is the end-point of a disabling process that starts, for most of us, when we're about 25. We'll be working, but we'll be doing more grocery bagging than particle physics.

Maybe we should think about how to make the less cognitive life more appealing. Maybe we ought to think about how society supports those with cognitive disabilities at all ages ...

How much of America's healthcare crunch is dementia care?

US healthcare costs were 2.6 trillion in 2010; about 18% of the 2011 US economy. Of that, dementia care costs about $200 billion, or about 8% of our total health care bill.

Demographics, and our failure to prevent brain deterioration, means dementia costs will grow. Since demented patients often exhaust all personal and family financial resources, these costs will show up as medicaid expenditures.

Even so, dementia is less of a problem than I had long thought. Even if costs were to increase by another 50% over the next decade, it still wouldn't break the bank.

Faced with the facts, I'm now forced to examine my unexamined assumptions. I can now imagine why dementia might turn out to be a bit of a bargain.

Many, if not most, dementia patients no longer receive aggressive medical care. They do need hands-on care, but in the modern economy there's no lack of people reasonably happy to do that work for comparatively little money. Demented people don't eat that much, and they don't require costly ingredients or food preparation. They don't demand the latest gadgets or costly bandwidth or cutting edge architecture or modern art on the walls. They can live where land is cheap.

In many ways, demented people are cheaper to maintain than non-demented people of similar ages. Given that neither produce wealth, from an economic accounts perspective dementia might be a money-saver.

Even as our dementia population grows, increasing costs may be offset by advances in robotics and remote monitoring, and, in time, by widespread acceptance of euthanasia [1].

Of course dementia and pre-demential can bankrupt individual families, but in our income skewed economy those bankruptcies don't add up to all that many billions.

To answer my title question then, dementia care does not appear to be a uniquely large part of our healthcare crunch. Obesity, for example, may be more important.

That's too bad, because many of us have a personal interest in a business case for dementia prevention...

[1] I want my kids to have a robust financial incentive to pull the off switch on my future demented self.

Exercise, weight loss and dementia

It's not that exercise doesn't work as a weight loss method, it's just inefficient ....

Weighing the Evidence on Exercise - NYTimes.com:

... When researchers affiliated with the Pennington center had volunteers reduce their energy balance for a study last year by either cutting their calorie intakes by 25 percent or increasing their daily exercise by 12.5 percent and cutting their calories by 12.5 percent, everyone involved lost weight. They all lost about the same amount of weight too — about a pound a week. But in the exercising group, the dose of exercise required was nearly an hour a day of moderate-intensity activity, what the federal government currently recommends for weight loss but “a lot more than what many people would be able or willing to do,” Ravussin says."

An hour a day would be wonderful -- if my kids were grown.

The NYT article has the complex details. The effect of exercise on weight varies by age and gender, and between individuals as well. In general, however, it's not a good way to lose weight. Diet is more efficient.

On the other hand exercise seems to be essential to keeping weight stable after a weight loss diet. How and why? Nobody knows for sure.

Sitting turns out to be really, really, bad. We've had hints of that over the past years, but now it's getting pinned down. We don't know why, but sitting promotes obesity.

Incidentally, it's all harder for women. But you knew that.

Elsewhere in the NYT, Olivia Judson deepens the cheer with claims that obesity causes brain damage. She's a bit below her par though; she obscures correlation with causation in the interests of more hits(she well knows the difference, so two demerits to her). It is likely that obesity is associated with early dementia, but it's also associated with lower socioeconomic status, lower IQ, and the anger of the gods.

For a contrary opinion, see Gina Kolata (also NYT) in 2007.

On the other hand, there's a weird association between exercise and brain function, even though I didn't believe it years ago. Exercise seems to help the health of neurons associated with cognition and memory in various animals -- for no particularly good reason. Since exercise is associated with lower obesity (in both directions) this further murkens the muddies.

Exercise also seems to help sleep, and I do suspect that sleep will turn out to be very important for brain health. Since obesity does impact sleep quality there may be an effect of obesity on the brain both by diminishing interest/ability to exercise and by worsening sleep quality.

Lastly, the idea that brain activity (bridge, crosswords, etc) slows dementia seems to be, at long last, good and dead. It doesn't work. Forget the bridge, forget the crosswords, go for a walk.

To sum it all up, my best guess at how this will all turn out:

• Sleep is more important for brain health than we've imagined.
• Exercise is more important for brain health than I thought 4-7 years ago. (I like to exercise, so it wasn't a prejudice against activity. It's just weird science.)
• Exercise helps both sleep and brain health - so it's a double good. It doesn't lead to weight loss, but it's essential to maintain a stable weight.
• We all need to diet all the time, so we need cultural and industry changes to make that very hard activity easier.
• Obesity is almost inevitable in a food rich world, especially when we eliminate smoking and increase sitting (at computers). We need a miracle drug, we need cultural changes, we need mobile devices, we need gas to hit $10 a gallon.
• Sitting is oddly bad for us. We should all be standing and walking.
• Try not to get a concussion (but almost all enjoyable exercise increases head injury risk :-). Don't let your kids play football (which will eventually go the way of boxing).

See also:

• BBC NEWS | Health | Creatine 'boosts brain power' 2003: Right. This went nowhere. A good reminder of how worthless most press releases are. We're still hearing about the huge onslaught of cognitive enhancer abuse, but it's mostly media imagination.
• Obesity increases dementia risk: Winner of stupid medical article of the month 2005: Early reports on the obesity/dementia causal relationship. I'm very skeptical then. I still am on the obesity side of things.
• Exercise and Alzheimer's: How to fix the demented media 2006: I really didn't believe this particular correlation, but since then it's shown up in more persuasive animal studies.
• Alzheimer's: there's not much you can do about it 2006: Head injury avoidance remains important -- but also lifestyle constraining. We all die one way or another!
• Exercise and cognition - I'm still skeptical 2007: I'm starting to wonder if I was wrong to dismiss a causal relationship between exercise and brain health
• Skinnies burn fast, plumpies less demented 2007: In this study the elder skinnies became demented faster than the pleasingly plump.
• Delaying the inevitable onset of Alzheimer's: exercise is the new best hope 2008: When I admin that it does look like exercise is oddly good for brain health.
• Wasting money: Ginkgo biloba joins the pile 2008 - Anyone remember when Gingko biloba was going to help dementia? Fail.
• Dementia is normal - and what that means: 2009 - We're beginning to realize dementia really is inevitable -- though there's still hope to push it back. (Death and homeliness are also inevitable)
• Avandia (rosiglitazone) for Rat Alzheimer's Prophylaxis?! 2006 - It didn't do too well in human trials. It also promotes obesity, which is kind of interesting.
• Dietary supplements stop dementia in beagles? AAAS proceedings 2004 - Nothing came of this!

Dietary supplements stop dementia in beagles? AAAS proceedings

In beagles, at least, there's evidence that diet can impact brain health ...

Economist.com | Dogs and medicine - Anti-oxidant anti-dementia therapy (for Beagles): Vitamin C, Vitamin E, alpha-lipoic acid, acetyl-l-carnitine.

... Carl Cotman and his colleagues at the University of California, Irvine, have been using beagles to investigate the effects of diet on the decline of brain function that accompanies ageing. Dogs are a useful stand-in for people in such experiments because the way memory declines in the two species seems comparable. Memory loss in dogs is accompanied by the formation of so-called amyloid plaques in the brain. Rodents, the usual stand-in mammals used in medical research, do not tend to accumulate such plaques as they age. In people, amyloid plaques are one of the symptoms of Alzheimer's disease.

... Dr Cotman wanted to know whether a diet rich in antioxidants, such as vitamins C and E, could relieve the symptoms of an ageing brain. Oxidative stress within the brain, which causes the production of molecules known as free radicals, increases with age. Free radicals can damage—and eventually kill—brain cells.

The results astonished the researchers. Not only did the antioxidant-rich diet halt age-related decline, it actually reversed it. While beagles on a normal diet continued to lose their cognitive abilities as they got older, those on the experimental diet showed improvements in learning and memory. These dogs could do much more complicated tasks, and made fewer mistakes. They could also re-learn tasks that they could do when they were younger, but had forgotten. And the diet (which, besides the vitamins, contained two food supplements called alpha-lipoic acid and acetyl-l-carnitine, that help to stop free radicals forming in the first place) also reduced the accumulation of amyloid plaques in the beagles' brains...

Ok. Why wasn't this a headliner in all the science summaries I review? There are so many implications of this research.

First, what's with dogs? I love dogs as much as the next geek, but they are starting to seem a bit odd. How much do they have in common with humans, anyway? In a previous posting I joked about dogs being a synthetic species designed to civilize pre-agricultural humanity...

Lunatic speculation aside, there are other implications here. Such as ...

1. Would I add this to my elderly dog's dinner?
2. Would I recommend it to everyone over 80 with memory problems?
3. Will I (44yo) start taking it myself?

But first, the caveats (lots of them):

1. Results like this are often misinterpreted or reversed on appeal. On the other hand, this isn't the first result of this sort, only the most dramatic.
2. When a "natural" "supplement" alters physiology, it's a drug. These substances are being administered in doses much higher than in a human or canine diet. They're acting like medications, "natural" or not, they're drugs. Most drugs have side-effects and drug interactions, good sides and bad sides. These will be no exception.
   We don't really know what role antioxidants play in disease. In 1996 the CARET study found an increased rate of lung cancer among clinical trial smokers taking antioxidants. Since then researchers have wondered if antioxidants are a key part of the tumor surveillance system. So one big caveat is the relationship between Alzheimer's dementia and brain tumors. What if suppressing oxidative stress reduced the risk of plaque-associated dementia, but increased the risk of brain tumors? That would not be a great trade-off.
   

And now, the opinions:

1. If my dog Molly, aged 14, didn't have a terminal disease, I'd add it to her diet. This is about as good evidence as we'll get for dogs.
2. It's very tempting to consider for elderly people experiencing early Alzheimer's disease. A few tabs of ibuprofen, some antioxidants … . Dementia is a devastating disease, and many people would assume many risks to avert it. But see the caveats above. What if the therapy increased the risk of strokes, or lung cancer? What about interactions with other medications? Does one need all the supplements, or just some of them? How critical is the balance? Could an unbalanced regimen worsen the underlying process? How does this really work, anyway? Above all, how similar are beagles to people? We may not know the answer to these questions for decades.
3. It's a huge leap from dogs to middle-aged humans. See all of the above. True, my memory isn't what I'd like -- but I'm probably at average risk for age 70-80 dementia, which implies significant impairment starting in about 10 years. Again, what if this antioxidant therapy knocked out a major component of the body's tumor suppression mechanism? OTOH, if I were at high risk for impairment within a 10 year time frame, I'd be phoning my neurologist now. Just to get them thinking.

Bottom line, very interesting. Alzheimer's is one of the major causes of dementia. Preventing Alzheimer's would, all by itself, resolve our social security and medicare crises. It would mean more people could be economically productive longer.

Exercise and Alzheimer's: How to fix the demented media

I read yet another bulletin declaring that "exercise can prevent alzheimer's". Sigh. The elderly who exercise 3 times a week are 50% less likely to be diagnosed with dementia. All that means is that it's worth funding more research. My bet is that a loss of commitment to exercise is an early indicator of a dementing process.

Some of the stupidest coverage came from the Wall Street Journal. I was feeling annoyable today, so I did a quick study. Someone who needs a pub should write this up as a letter to Lancet. I bet they'd get a nice cite.

I googled on the news: exercise alzheimer's - Google News:

Exercise Research
WOWT, NE - 18 hours ago
... More research is needed to better understand how exercise may help protect against diseases like Alzheimer's, but for now researchers say one thing is clear ...

Research Notebook OregonLive.com, OR - 6 hours ago ... years, 158 had developed dementia, including 107 diagnosed with Alzheimer's disease ... older adults who exercise Another study that looked at physical activity in ...

Study: Exercise May Reduce Risk of Alzheimer's Disease ABC News - Jan 16, 2006 ... Researchers emphasize that this study is not proof that exercise reduces the risk of Alzheimer's disease, but they say the results are consistent with several ...

Alzheimer's Disease May Be Prevented With Exercise Fashion Monitor Toronto, Canada - 23 hours ago ... The six core strategies to prevent Alzheimer's disease include exercise, diet, a program of vitamin and herbal supplementation, regular brain stimulation, a ... Exercise Not Enough to Prevent Alzheimer's Disease PR Web (press release) all 3 related »

Exercise Significantly Reduces Risk of Dementia in Senior Citizens SeniorJournal.com, TX - Jan 16, 2006 ... growing evidence that exercise – particularly if it starts early and is maintained over time - is beneficial in preventing dementia and Alzheimer’s disease ...

Health Roundup: Alzheimer’s And Exercise, Sibling Drinking ... NBC 10.com, PA - Jan 16, 2006 ... The things that reduce our risk for Alzheimer's are: exercise, reducing our cholesterol with statins, eating a lower fat diet and lowering our blood pressure ...

Exercise associated with reduced risk of dementia in older people
EurekAlert (press release), DC - Jan 16, 2006
... Additional study also may provide information on the possible merits of varying types of exercise. For information about Alzheimer's disease, visit the ...

It turns out that about half of the top-ranking Google results used "may" and a few even used "associated with" (they get five stars). The rest, alas, were as dismal as the Wall Street Journal.

So here's how to shame the media into doing better. JAMA should run a report after each report of a finding associated with reduced cancer, dementia, etc. The journalist can simply execute a Google News search and extract the titles. Titles are then ranked for words like "may" and (best) "associated with". Report the results by dividing press into "Good", "Bad" and "Ugly" categories.

After six months on the "Ugly" list, the Wall Street Journal gets a special prize.

Eventually, they improve.

Alzheimer's and Amyloid: How even a perfect aducanumab could help some and hurt others.

Representational drift, if validated, tells us that a memory is a set of relationships, not the specific neurons that embody those relationships. This sentence might be rendered in electrons or ink, but it has the same meaning.

Reading an article about this reminded me about an old concern with drugs that aim to treat Alzheimer's by reducing amyloid accumulation in neurons. Drugs like the recently approved (and seemingly minimally effective) monoclonal medication aducanumab. The root problem is that we don't know why neurons accumulate amyloid. There's been a growing suspicion over the past few years that amyloidization might in some way be helpful.

I wrote about one way this might play out in a twitter post which I've revised here:

Representational drift reminds me of a theoretical problem with aducanumab and amyloid therapy for Alzheimer’s dementia. It begins with recognizing that we don’t know why neurons accumulate amyloid. 

Many suspect amyloid has a physiological reason to appear in neurons. Suppose, for example, amyloid is the way old crappy neurons are "retired" from forming memory relationships. Amyloidization would then be the brain equivalent of marking a SSD region as unusable. 

A system like this would have 2 kinds of bugs. It might be too aggressive or not aggressive enough. 

If the retirement mechanism is too aggressive then neurons will be amyloidized prematurely. They could have still formed useful memories, but now they're dead. The brain can only produce so many neurons so it runs out prematurely. Early dementia develops. In this case a drug that cleared amyloid could help -- as long as it wasn't too aggressive. The balance may be fine and hard to get right. 

If the retirement mechanism is too permissive then a lot of flaky neurons accumulate without much amyloid. Dementia follows from this too -- but it might look clinically quite different. In this case a drug that cleared amyloid would make the dementia worse! Even more flaky neurons would accumulate. 

Even if the balance is just write we do run out of viable neurons. Even a very healthy centenarian has only a fraction of the cognition they once had. Again, in this case, an amyloid clearing drug would make the brain worse. 

If this was the way the brain worked then an amyloid reduction drug would make some dementia worse and some better. The net effect would be quite small -- even if the medication worked perfectly and was dosed correctly. 

All speculative. Come back in 5 years and see how it turned out.

ACE inhibitors and dementia: radiation protection?

These kind of loose association studies are a dime a dozen, and usually misleading. They're digging data obtained for other reasons to look for an association. What makes it interesting, however, is the animal study:

Some heart drugs may slow mental decline with age | Health | Reuters:

... The study found a link between taking these "centrally acting" ACE inhibitors and lower rates of mental decline as measured by the Modified Mini-Mental State Exam...

For each year that subjects were exposed to centrally acting ACE inhibitors that enter the brain, the decline in test results was 50 percent lower than the decline in people taking other kinds of high blood pressure pills...

... Centrally acting ACE inhibitors include captopril (Capoten), fosinopril (Monopril), lisinopril (Prinivil or Zestril), perindopril (Aceon), ramipril (Altace) and trandolapril (Mavik). [jf: several of these are off-patent now]

Sink decided to investigate the effect of centrally acting ACE inhibitors on dementia risk after her Wake Forest colleagues found the drugs protected rats from brain injury due to radiation. She presented her findings May 5 at the American Geriatrics Society's annual meeting in Seattle.

She and her colleagues looked at a subgroup of 1,074 men and women participating in a study of cardiovascular health who were taking drugs to treat hypertension and were dementia-free when the study began.

While the centrally acting ACE inhibitors did slow cognitive decline, as Sink had hypothesized, the non-centrally active ACE inhibitors that don't reach the brain actually boosted the risk of developing dementia by 20 percent, although the effect didn't reach statistical significance....

The radiation protection effect is what made my ears perk up. The rest of this is thin stuff, enough only to justify further work. We do have animal models for dementia, so that is the place to look next. The "risk increase" numbers are probably random error in this type of study.

Obesity increases dementia risk: Winner of stupid medical article of the month

BBC NEWS | Health | Obesity increases dementia risk

I have a bad feeling this news story actually reflects the article. I think it's extraordinarily unlikely that obesity causes dementia; it will be very, very hard to extract a dementia/obesity relationship from obesity/IQ/wealth and IQ/dementia relationships. I'd be astounded if the authors were able to control for an obesity/IQ correlation.

A reasonable article on the science of slowing aging

Most of the popular literature on slowing senescence tends to extravagant predictions. By comparison, this brief 5/6/07 NYT article is quite modest. If everything works today's 30 year olds might get another 10 years, and today's 10 year olds might get more.

I also like the description of the aging brain, though I think they're being optimistic about the relationship between disability in your 70s and forgetting your keys in your 40s. Emphases mine.

Baby Boomer - Aging - Longevity - Dementia - New York Times

May 6, 2007

Participants: Lenny GUARENTE, PH.D.: Novartis professor of biology at M.I.T. and author of “Ageless Quest: One Scientist’s Search for Genes That Prolong Youth.”; Robert N. BUTLER, M.D.: Founding director of the National Institute on Aging, a founder of the Alzheimer’s Disease Association and winner of a Pulitzer Prize in 1976 for “Why Survive? Being Old in America.” He heads the International Longevity Center.; SARA DAVIDSON: Author, most recently, of “Leap! What Will We Do With the Rest of Our Lives?”

... LENNY GUARENTE: The research that I’m involved in is not about extending life after people are infirm. I don’t think of life span as the gold standard. The gold standard is health span. All the indicators from the laboratory are that the genes we’re studying and the kinds of drugs we would be developing would extend health span. If you can extend health span, and you also happen to extend life span, so be it. That’s a side benefit...

... The genes we study counteract aging. First we studied yeast cells, and it took us eight years to identify a gene called SIR2, which protects the cells from damage during the aging process. Then we did a similar experiment in a more complex critter, the roundworm, and what was remarkable is, we identified the same gene. That told us that this type of gene is performing an antiaging function broadly in nature.

Do humans have this gene?

GUARENTE: There’s one gene in our genome, SIRT1, that would be a dead ringer for this one — the technical term is ortholog — but we also have six other genes that have a related sequence to this. They’re called sirtuins, and they’re all going to play a role, but I think the dead ringer is undoubtedly the most important based on experiments that have been done.

... We think the sirtuin genes are there to recognize lack of food or other stressful situations and to spring into action to create a physiology that will promote longevity. The evolutionary value is that in times of stress — food scarcity, for example — this gene would slow down the aging process and keep you alive longer, so that when times are better, you could reproduce. ..

... In our lifetimes, could this happen?

GUARENTE: I think one can expect perhaps another decade of robust health...

... How close are we to such a drug being available?

GUARENTE: Ten, maybe 15 years. I think the drugs that aim at sirtuins, for example, will be tested initially for a particular disease, say, diabetes. And it will turn out that the drugs have broader benefits than one initially imagined.

What about resveratrol? There has been a lot of publicity about this substance that’s found in red wine. Does it do the same thing as calorie restriction?

GUARENTE: It’s a natural product, made by plants, and recently one of my former postdoctoral students, David Sinclair, found that resveratrol can regulate the activity of SIRT1.

Do you take resveratrol?

GUARENTE: No, partly because neutraceuticals are not regulated by the F.D.A. If I was sure of the quality control, I would consider it, but I’m still not certain I would do it, because you may have to take a lot — one or two grams a day.

What intrigues me is that I read that if fruit flies are fed resveratrol, they live longer and can eat all they want...

... BUTLER: .. we don’t even have the means to evaluate or measure whether a substance prolongs life. We have yet to create biomarkers that would measure, short of death, actual changes in the body that reflect aging...

... BUTLER: There are many types of dementia, which result from different causes. The most common is Alzheimer’s, which is characterized by neurofibrillary tangles — misshaped proteins — and plaques. The second most common is multi-infarct dementia, which is the result of small, repeated strokes. Scientists who are studying Alzheimer’s have differentiated three categories for research purposes. The first is what’s called age-associated memory impairment. These are the kinds of things ordinary people are going through: forgetfulness, not remembering why you’ve walked into a room or where you put the paper you were just holding in your hand. If you’re in this category, we have no data that suggest you’re necessarily on your way to Alzheimer’s.

The second category is mild cognitive impairment — getting confused on the street, not remembering you’re supposed to have coins when you get on a bus. At that point, the conversion rate to the third — full-blown Alzheimer’s — sadly, is very high. After three years, about half the people will not be able to take care of themselves, but the conversion is not total. Some people plateau and seem to go on for a long time.

How do you know when to be concerned?

BUTLER: One of the rules we use as clinicians is: if you forget your keys, that’s not so terrible, but if you forget what a key is for, that becomes serious...

... BUTLER: I’m afraid there’s a lot of romance in the literature suggesting that we can stop Alzheimer’s disease by cognitive exercises...

... There’s a distinction between advancing life expectancy and breaking the genetic barrier. Every species has a predetermined genetic life span. Certain fish live about a year. Some turtles live 200 years. Humans have about 110, 120 years at the outside of their genetic life span. We’re talking about increasing healthy years within that life span.

But wait you say -- what about us boomers feeling the steel jaws closing? Ask not for whom the bell tolls ... I do think there's hope that we'll delay our cognitive disability by a few years.

BTW, bravo to Butler for breaking the happy illusion that crossword puzzles are going to slow dementia development. It's such a sweet idea, but it's silly.

del.icio.us tags: dementia, aging, senescence, SIR2, resveratrol

Another nail in the coffin for the Alzheimer's amyloid hypothesis

Researchers bet careers, and pharmas bet billions, that amyloid plaques caused neuronal dysfunction in Alzheimer's disease. If the plaques could be prevented, you could prevent the disease.

Those bets have been going bad over the past four years. Today Lilly lost another bundle ....

Lilly Halts Alzheimer’s Drug Trial - Prescriptions Blog - NYTimes.com

... semagacestat, did not slow progression of the disease and was associated with a worsening of cognition and the ability to perform the tasks of daily living....

... The failures, and particularly this newest one by Lilly, could raise questions about the validity of the prevailing theory about Alzheimer’s, which is that the disease is caused by the accumulation of so-called amyloid beta plaques in the brain. 

 Lilly’s drug was designed to reduce the body’s production of the plaques by inhibiting the activity of an enzyme, called gamma secretase, that is believed to play an important role in formation of the plaque...

The contrary hypothesis was that the characteristic amyloid plaques of Alzheimer's disease were either a consequence of the disease process, or perhaps even some sort of protective measure. That hypothesis has been getting more support.

This latest result is just one example of all the recent bad news on delaying age-related dementia in general, and Alzheimer's disease in particular. We now know that "mental exercise", "social prophylaxis" and so on don't delay disease onset. We have shown that most treatment medications are, at best, marginally effective and poorly tolerated. We have no preventive meds -- estrogen, statins, non-steroidals and so on all are unimpressive.

We do know that head injuries are bad - worse than we imagined. Not only are concussions associated with Alzheimer's dementia, they're also associated with motor neuron disease. Most contacts sports, including American football and "soccer" will look very different in 10 years.

We believe, bizarrely, that exercise really does preserve the brain. We don't have a solid mechanism for that.

We also have tests that can diagnose Alzheimer's early, which is a good way to ensure you'll never be able to buy long term care insurance. Otherwise the tests look pretty pointless.

We need some good news. Forget the blather about social security -- that's not the crisis. That's just a GOP distraction. The crisis is pre-dementia and dementia in an aging post-industrial America.

Die smarter? Longevity genes, Alzheimer's and gambling with Faust

The 'related links' section of this SciAm summary are also of interest:

Science & Technology at Scientific American.com: Single Gene Could Lead to Long Life, Better Mental Function -- A variation of a gene that controls the size of cholesterol molecules in the bloodstream is common among elderly Ashkenazim who remain mentally sharp

... Those centenarians who passed were two to three times more likely to have a common variant of a particular gene, called the CETP gene, than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts.

The CETP gene variant makes cholesterol particles in the blood larger than normal. The researchers suggest smaller particles can more readily lodge in the lining of blood vessels, leading to fatty buildups, which are a risk factor for heart attacks and strokes.

Whether or not this gene variant protects the brain by preventing this buildup, or through some other mechanism, remains uncertain, says Barzilai. Future research should also investigate whether this gene has an effect on dementia associated with Alzheimer's disease, says pathologist and human geneticist George Martin at the University of Washington.

Pharmaceutical companies are currently developing drugs that mimic the effect of this gene variant, says Barzilai. Unfortunately, one known as torcetrapib, manufactured by Pfizer, was pulled in December due to increased death and heart problems among study subjects, "but others in development aren't seeing that, so it might just have been a problem with that drug," says Barzilai. "If not, it's a question people might face--whether or not people want to prevent Alzheimer's even if there's a small risk of getting a heart attack.

Fascinating basic science, but like all good basic science it mostly raises questions. For all we know now this gene doesn't so much provide longer life, as kill off those who lack some other compensatory gene that provides benefits. It might, for example, be primarily an Alzheimer's reduction gene that also increases the risk of heart attacks, so if you sample elderly people with the gene you're finding those who have some other factor that offsets the heart attack effect.

Alas, many "beneficial" genes turn out to have a Faustian component -- such as trading slower aging and faster healing for more cancer. (Turns out mice do this big time -- if they're not killed they almost always die of cancer -- but they heal fast.)

Which brings us to Barzilai's comment. The promise of modern pharmacogenetics is really about optimizing the Faustian bargain. So you make a "deal with the devil", but the deck is stacked in your favor. If your MI risk is low but your dementia risk is high, then you might opt for an anti-dementia drug that increases the risk of MI. If your dementia risk is high, and your MI risk is average, you schedule bypass surgery in 8 years. Who needs recreational bingo when you can gamble on this scale?

Bexarotene clears amyloid plaques in ApoE4 defective mice - and an Alzheimer's review

While it's true that we can cure just about anything in mice (at least once), this is still remarkable ...

BBC News - Alzheimer's brain plaques 'rapidly cleared' in mice

... Scientists at the Case Western Reserve University in Ohio were investigating ways of boosting levels of ApoE, which in theory should reduce levels of beta-amyloid.

They tested bexarotene, which has been approved for use to treat cancers in the skin, on mice with an illness similar to Alzheimer's.

After one dose in [genetically engineered mice with dysfunctional ApoE4] young mice, the levels of beta-amyloid in the brain were "rapidly lowered" within six hours and a 25% reduction was sustained for 70 hours...

What's remarkable is the speed of the result, and that the drug is already FDA approved for another use. That means, although as chemotherapy agent for mycosis fungoides it has nasty side effects, Bexarotene will be very soon studied in humans with advanced dementia. We may find, however, that the drug is primarily useful for people who have remarkably poor ApoE4 directed amyloid clearance.

The role of amyloid in Alzheimer's dementia was well described in a 2010 NYT review ...

Insights Give Hope for New Attack on Alzheimer’s - NYT 12/13/10 - Kolata

... most people with Alzheimer’s seem to make perfectly normal amounts of amyloid. They just can’t get rid of it

... Researchers have also found that amyloid, in its normal small amounts, seems to have a purpose in the brain — it may be acting like a circuit breaker to prevent nerve firing from getting out of control. But too much amyloid can shut down nerves, eventually leading to cell death. That means that if amyloid levels were reduced early in the disease, when excess amyloid is stunning nerve cells but has not yet killed them, the damage might be reversed....

... With Alzheimer’s disease, Dr. Bateman discovered, beta amyloid is made at a normal rate, but it hangs around, draining at a rate that is 30 percent slower than in healthy people the same age. And healthy older people, in turn, clear the substance from their brains more slowly than healthy younger people...

... beta amyloid seemed to be part of a nerve cell feedback loop. A nerve will start firing, but under some conditions, the signal can get too intense. Then the nerve releases beta amyloid, bringing the signaling down to normal levels, at which point the nerve stops releasing beta amyloid... [especially in the 'default network']

... There may be another way to protect nerves from too much beta amyloid, and it involves a different protein linked to Alzheimer’s. Problems with it show up in the brains of Alzheimer’s patients later, after there has already been a buildup of beta amyloid.

The protein is tau, an integral part of normal cells. It becomes tangled and twisted in Alzheimer’s, after cells are already dying, looking like strands of tangled spaghetti...

... New studies by Dr. Lennart Mucke, a neurology professor at the University of California, San Francisco, and director of the Gladstone Institute of Neurological Disease there, and others suggest that tau facilitates beta amyloid’s lethal effects. In genetically engineered mice and in laboratory experiments, the researchers found that without tau, beta amyloid cannot impair nerve cells...

...Amyloid was in ...  the default network. It is used not only in daydreaming but in memory and in the sense of self...

... The default network is costly for the brain to run, using huge amounts of glucose, Dr. Raichle said. And one indication that a person is getting Alzheimer’s is that in scans, the brain’s glucose use is markedly lower. The observation that Alzheimer’s attacks the default network, then, explains the observation that a low use of glucose by the brain is associated with Alzheimer’s disease.

... Beta amyloid synthesis increased when they were awake, when the default network is most active, and decreased when they slept...

... the less active the person’s brain, the less beta amyloid it made. That made the researchers ask whether something similar was happening during sleep — the default network was less active, so perhaps less beta amyloid was being made. If so, the implication, which Dr. Holtzman is studying, is that people who are sleep-deprived might be at greater risk of Alzheimer’s.

I am prone to believe in the sleep loss/dementia connection, I wrote about that in 2008 and more emphatically in 2010.

The role of ApoE4, exercise and dementia was also highlighted two weeks ago in the NYT ...

How Exercise May Keep Alzheimer's at Bay - NYT 1/18/2012

... Most of those who carried the APOE-e4 gene displayed much larger accumulations of amyloid plaques than those without it.

Unless they exercised. The carriers of the gene who reported walking or jogging for at least 30 minutes five times a week had plaque accumulation similar to that of volunteers who were e4-negative. In essence, the APOE-e4 gene carriers mitigated their inherited risk for developing Alzheimer’s by working out. Or, as the study authors wrote, a “physically active lifestyle may allow e4 carriers to experience brain amyloid levels equivalent to e4-negative individuals.”..

... An overwhelming majority of the people in the study were sedentary, and for them, an inactive lifestyle seemed to be accelerating the accumulation of amyloid plaques. Those with the e4 variant who rarely or never exercised had the most plaques, putting them at heightened risk for the memory loss of Alzheimer’s in the years to come.

From another angle, another recent article points to a prion like spread of malformed tau protein as a critical component of Alzheimer progression. (see tau references in the 2010 article) ...

Alzheimer’s Spreads in the Brain Like a Virus, Studies Find - NYT Kolata 2/1/2012

Alzheimer’s disease seems to spread like an infection from brain cell to brain cell, two new studies in mice have found. But instead of viruses or bacteria, what is being spread is a distorted protein known as tau...

The studies, done independently by researchers at Columbia and Harvard, involved genetically engineered mice that could make abnormal human tau proteins, predominantly in the entorhinal (pronounced en-toh-RYE-nal) cortex, a sliver of tissue behind the ears, toward the middle of the brain, where cells first start dying in Alzheimer’s disease. As expected, tau showed up there. And, as also expected, entorhinal cortex cells in the mice started dying, filled with tangled, spaghettilike strands of tau.

Over the next two years, the cell death and destruction spread outward to other cells along the same network. Since those other cells could not make human tau, the only way they could get the protein was by transmission from nerve cell to nerve cell...

... beta amyloid, which accumulates in the brain of Alzheimer’s patients, forming hard, barnaclelike plaques. But beta amyloid is very different from tau. It is secreted and clumps outside cells. Although researchers have looked, they have never seen evidence that amyloid spreads from cell to cell in a network.

Still, amyloid creates what amounts to a bad neighborhood in memory regions of the brain. Then tau comes in — some researchers call it “the executioner” — piling up inside cells and killing them...

... it may be necessary to block both beta amyloid production, which seems to get the disease going, and the spread of tau, which continues it, to bring Alzheimer’s to a halt...

These are exciting times in dementia research, particularly given the discouraging state of the art only three years ago.

Alas, good news can't come fast enough for the 40+ set - our brains start running downhill fast at around age 45 [1]. While we wait to see if anything will come of this, our take away lessons are ...

• Avoid head injury.
• Exercise. If somehow you know you have problematic ApoE4 this seems utterly essential. Probably good for all of us.
• Sleep 8 hours a night. (Speculative, but I bet this will be true).

[1] Yes, raising the retirement age is a sick joke.

Sudden death in frontotemporal dementia - a clue to sudden infant death syndrome?

A friend of mine recently lost a friend and neighbor to Frontotemporal dementia (Picks disease), a particularly loathsome form of dementia (but aren't they all?) with a 50% occurrence risk in children of affected persons.

He mentioned his friend died fairly suddenly. Puzzling, I thought. Why suddenly?

Turns out that's common in FTD:

[Initial symptoms, survival and causes of death in...[Fortschr Neurol Psychiatr. 2007] - PubMed Result: "Causes of death were varied, but pneumonia and sudden unexplained deaths were particularly frequent."

Hmm. Sudden death. Brain disease. Could there be a clue in FTD to the causes of Sudden Infant Death Syndrome?

Well, there are lots of Google hits on the paired terms, though the associations seem coincidental. On the other hand, a Pubmed search combining both terms had no hits (today). So maybe this research is yet to be published ...

Terry Pratchett on fading from dementia

via Pharyngula, I find Terry Pratchett has written an article for the journal of mental health. His goal is make dementia something we can actually talk about, as a start to doing something about it.

Informa Healthcare - Journal of Mental Health - 19(4):363 - Full Text

.... have posterior cortical atrophy or PCA. They say, rather ingenuously, that if you have Alzheimer's it's the best form of Alzheimer's to have. This is a moot point, but what it does do, while gradually robbing you of memory, visual acuity and other things you didn't know you had until you miss them, is leave you more or less as fluent and coherent as you always have been.

I spoke to a fellow sufferer recently (or as I prefer to say, ‘a person who is thoroughly annoyed with the fact they have dementia’) who talked in the tones of a university lecturer and in every respect was quite capable of taking part in an animated conversation. Nevertheless, he could not see the teacup in front of him. His eyes knew that the cup was there; his brain was not passing along the information. This disease slips you away a little bit at a time and lets you watch it happen...

I suspect Pratchett knows it's likely too late for him, but this is something he can do (he also donated $1 million, he's an honorably rich man).

I've read over 45 of Pratchett's books, he's written 47. I think I've missed one or two of his very earliest, before he was famous. If this were a just world, he'd be considered for the literature Nobel. It's not too late.

Pratchett writes "fantasy" for the same reason Banks writes science fiction. It's a way to write about subjects too big for conventional literature. Yes, he also likes to entertain.

Wikipedia has a full list of his Discworld novels. You can start just about anywhere, though the later novels do expect that you've at least red the Discworld wikipedia page. My favorites are between 1990 and 1998. Small Gods (1992) and Carpe Jugulum are a good pair, and this time of year Hogfather is a family favorite. All of the books are available through the St. Paul public library, and we own about a dozen or so. They are well worth rereading.

The Onion covers McCain's bus problem

The Onion goes where others fear to tread.

They have a satirical news story about John McCain Accidentally Left On Campaign Bus Overnight.

Fortunately passer-byes find Cindy's number in his pocket, and she rescues the confused senator.

Today there are 571,000 hits on "McCain dementia".

A vote for McCain is a vote for President Palin.

Update 5/11/10: McCain's political career seems to be ending, and his statements are increasingly erratic -- but there's really no mainstream media coverage of his cognitive state. We saw the same thing in Reagan's second term. He was clearly impaired, which seems pretty relevant, but the topic was forbidden.

John McCain has had quite a few head injuries, so dementia at his current age is extremely probable. Bob Vitray, writing in 2008, had a good summary ...

... His sport at Annapolis was boxing. He was knocked out at least twice in plane crashes. He probably suffered a concussion during his escape from the Forrestal fire. The North Vietnamese beat him and starved him ...

McCain has had an extremely eventful lPublish Postife, with more than his fair share of head trauma. He should retire now, and we should set aside his actions of the past few years as being a legacy of his dementia. The fault for those actions and statements falls on those who have encouraged him to continue in public life.

American crisis – imagining a way out

Scott (Dilbert) Adams can’t imagine any way American will survive its 21st century budget crisis.

 

This betrays a certain lack of historical perspective. We’ve been through worse, other nations have been through much worse. Compared to the American Civil War, the Black Death, or even the many versions of “great” Depressions we’re in pretty good shape.

 

Not that success is guaranteed, but it’s quite easy to imagine.

 

As a starting point, I’d suggest some subset of this list would suffice:

1. Political reform. I’ve got another post brewing on this. Fourteen years ago I satirized “public incorporation” of representatives, but now we have corporate persons with political rights. We’re in trouble. Many current Senators appear to have early dementia, and our political candidates are often lousy. We need to rethink who we elect, how we elect them, and how old they can be. We should draw on ideas from professional training and licensing and from jury selection.
2. Taxes. We’re going to raise taxes – a lot. We should do a Carbon Tax. We will do a VAT equivalent. We’ll do “death” taxes – again.
3. Immigration - Oh Canada: Canada figured this one out years ago. We have too many decrepit boomers. We  need to balance my generation with vigorous, energetic highly talented youth. So let them in based on professional and academic qualifications and business guarantees.
4. Inflation: 3% should help whittle down those foreign debts. Don’t say you weren’t warned China.
5. Give up on the Empire. The Soviets couldn’t afford their empire. Guess what? We can’t either.
6. Delay Dementia: We’re all going to have to work longer, but we can’t all bag groceries. For one thing, that job’s going to a robot someday. Unfortunately, normal brain aging means most of us won’t be good for much more by the time we’re 72. We need a ton of research into slowing the inevitable onset of dementia. (Ok, so if you die it’s not inevitable.)

Note that my list doesn’t include “controlling health care costs”. That one’s simply inevitable, so I don’t bother with it.

The disposable brain - lessons from our elastic axons

The human brain is misplaced. It ought to be inside our pelvic-abdominal cavity, where humans carry babies. Instead it's stuck at the top of a tall biped, fully exposed to all traumas.

Intelligent design, my ass.

Thanks to its bad neighborhood the poor brain is being constantly banged about. Every so often it gets plastered against its membranous sac, typically when a head meets an rapidly moving object such as a sidewalk or a baseball bat. This is not good for something with "the consistency of custard". Evolution has struggled to adjust (emphases mine) ...

The Brain: What Happens to a Linebacker's Neurons? | Carl Zimmer | DISCOVER

... axons are remarkably elastic. They can stretch out slowly to twice their ordinary length and then pull back again without any harm. Axons are stretchy due in part to their flexible internal skeleton. ... When an axon stretches, these microtubules can slide past one another. If the movement is gradual, the microtubules will immediately slide back into place after the stretching stops, with no harm done.

If Smith delivers a quick, sharp puff of air, however, something else entirely happens. Instead of recoiling smoothly, the axon develops kinks. Over the next 40 minutes, the axon gradually returns to its regular shape, but after an hour a series of swellings appears. Each swelling may be up to 50 times as wide as the normal diameter of the axon. Eventually the axon falls apart.

These kinks form, Smith believes, when microtubules are stretched so rapidly that they snap ... Normally, enzymes inside neurons are constantly taking apart microtubules and building new ones with the recycled parts. But now the enzymes attack the broken ends of the microtubules, causing the internal structure of the axon to dissolve...

... Smith’s findings could shed light on a common but puzzling brain trauma known as diffuse axonal injury. This happens when people experience sudden accelerations to the brain—from a bomb’s shock waves, for example, or from whiplash in a car crash ... When pathologists perform autopsies on people with diffuse axonal injury, they see severed axons with swollen tips, just like what Smith sees in his experiments.

Smith’s research also suggests that even mild shocks to the brain can cause serious harm. ... A moderate stretch to an axon, Smith recently found, causes the sodium channels to malfunction. In order to keep the current flowing, the traumatized axons start to build more channels.

Smith suspects that such a mended axon may be able to go on working, but only in a very frail state. Another stretch—even a moderate one—can cause the axon to go haywire ... The axon dies like a shorted-out circuit.

... Preliminary brain studies show that axons are still vulnerable even months after an initial stretch...

Just in case you're not depressed enough yet, wherever you read "axons" substitute the phrase "young axons". Any wagers on how well older axons stretch? Also note that "even months after" doesn't mean they're not vulnerable "years after".

It's interesting, after reading this article, to search PubMed with the phrase "microtubule amyloid axonal injury".  A 2006 paper looked at animal model transient accumulation of neurotoxic amyloid precursor protein after injury. Amyloid protein has, of course, long been associated with Alzheimer's dementia. Head injury is also strongly associated with dementia risk; head injury avoidance is about the only "intervention" known to reduce the risk of Alzheimer's disease. (Don't make too much of this injury/amyloid connection though, researchers have been banging on it since the 1990s. It's not straightforward.)

Short of radical genetic engineering, or spending our lives watching TV with thickly padded carpets, what can we do about our fragile brains? Sure, football is dead. Yes, soccer will lose the header. Sure we can change the rules of hockey. Yes, horseback riding is almost as crazy as riding donorcycles. But, really, have you watched any TV lately? There are worse things than dementia.

Today's helmets are not the answer. Current bicycle helmet designs, for example, don't materially change the rate of anterior impact deceleration. Their primary benefit is to facilitating head gliding and reduce abrasions; they aren't designed to reduce the deceleration injuries that matter -- without severing our wimpy cervical spines. (On road bikes effectiveness is further diminished by paradoxical automobile driver behavior.)

We need to revise our sports (so long NFL), but we also need much better helmets. Air bags anyone?

See also:

• Gordon's Notes: Helmets: good for inline, not so good for bicycling?
• Helmet: building a better bicycle/inline helmet - Ideas? - rec.bicycles.misc | Google Groups (2002)

CrossFit 58

I’ve had a habit around each birthday to review where I’m at with my exercise addiction. This past week was the 58th. I bought myself a Canon SL2 and Emily made me a fabulous Black Forest cake. So time for an update.

I started on the hard stuff at 53. I’d done some exercise before that - mostly road biking, nordic skiing, inline skating and other soft stuff. At 53 though, I fell into CrossFit. Actually, I was pushed. By a friend.

Four and a half years later I’m 58 and I’m still a regular at CrossFit St Paul. I average 3-4 CF workouts a week, mountain bike 1-2 times a week, and do 1-2 days a week of recovery weights or road biking or ice hockey or nordic skiing.

I’ve had soft tissue strains and pains from all of those things, but by now I’m good at rehab. I have a suite that covers hamstring/gluteal/“piriformis”, lower back strain, shoulder things, achilles stuff, chondromalacia patellae and more. “More” includes a familial arthritis syndrome affecting my hands and knees. Sooner or later that will do me in, but hydroxychloroquine seems to slow the progression. When it was diagnosed 2 years ago I figured I’d be out of CF by now, but the arthritis hasn't been a big deal yet.

I work the rehab into my workouts. It’s all one thing. Mostly I’m pretty good.

Over time I lost about 20 lbs of fat and gained about 5 lbs of muscle. Alas, at 58 I have no more muscle stem cells — those seem to go away in the 30s. I may yet get a bit stronger with practice, but not a lot. I’ve bumped up some of my weightlifting records, but recently my overhead squat and snatch have sucked. Seems the small amount of muscle I added to my shoulders came along with decreased range of shoulder motion. Gives me something else to work on.

I still can’t do consecutive double-unders, I have to mix singles and dubs. I may set a record for longest time practicing without success. It’s a coordination thing — I’ve always been clumsy but age sucks. I’ll try a fourth jump rope; some say a slower, heavier rope works better for the old. I have a rope for every occasion now.

I haven’t been able to do a muscle-up - neither bar nor ring. I work on it. Maybe someday.

I got into this to keep my formerly bad back better and because the only things that seem to slow dementia onset are sleep and exercise. I need to slow the dementia - family circumstances mean my brain has to work until about 85, when I can finally keel over and die. It’s too early to tell if it works for the dementia, but my back is pretty good.

Happily I enjoy CrossFit. I travel for work and always drop in on a CF gym — they are almost everywhere (not Hot Springs South Dakota though). I’m almost resigned to being the slowest and weakest person in the box.

It’s a living.

Dementia: is it really a disease?

So is Alzheimer's-type dementia really a disease?

Prevalence of Alzheimer’s Rises 10% in 5 Years - New York Times:

... The updated estimates, based on the rising occurrences of the disease with age, not new disease research, were released yesterday by the Alzheimer’s Association, along with a compilation of other information about a progressive brain disease that afflicts 13 percent, or one in eight people 65 and over, and 42 percent of those past 85...

...Mary Mittelman, an Alzheimer’s researcher at New York University, had mixed feelings about disproportionate attention to early onset Alzheimer’s disease. On the one hand, Dr. Mittelman said, these cases are such a small minority that she fears will take focus and resources “from the majority who are much older.” On the other, she said, 'because of the ageism of this society” far too many people still believe dementia to be part of normal aging and attention to this younger group will clarify that it is a 'real disease'.”

When 42% of people over 85 have advanced features of a prolonged process, is this a "real disease" or an aging process? The boundary here is pretty fuzzy. Nobody has the brain or body at 85 that they had at 45, much less 25.

My personal bias is that the "Alzheimer's process" is a "normal" part of aging, right up there with getting weak, flabby, and shorter. What varies, of course, is how fast it progresses, and whether one dies before or after the process becomes disabling (disability also being a fuzzy term -- many persons who we consider "able" at 85 are unable to do the work they did at 45).

The distinction between an aging process and a disease has a practical implication. In general, diseases are treatable, but aging is much harder to stop. If we accpet the model of an Alzheimer's "Process" rather than Alzheimer's Disease, then we can better judge how great our challenge is. We need to do more than arrest a disease, we need to slow the aging process of the human brain. The bright side is that there's been a lot of research lately that suggests that might be possible.