March 08, 2005
Mild Cognitive Decline In Old Age Sign Of More Severe Brain Disease
Slowing of minds in old people is a sign that a more serious brain disorder is developing.
CHICAGO - Mild cognitive impairment in older people is not a normal part of growing old but rather appears to be an indicator of Alzheimer's disease or cerebral vascular disease, according to a study published in the March 8 issue of the journal, Neurology.
"The study shows that mild cognitive impairment is often the earliest clinical manifestation of one or both of two common age-related neurologic diseases," said Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center and the principal author of the paper. "From a clinical standpoint, even mild loss of cognitive function in older people should not be viewed as normal, but as an indication of a disease process," said Bennett.
This is the first study involving a large number of subjects who were followed until they developed mild cognitive impairment or dementia, and then died. The study involved examining brain tissue from 180 people, including 37 with mild cognitive impairment, 60 without cognitive impairment, and the rest with dementia. All were Catholic nuns, priest or brothers who agreed to participate in the National Institute on Aging (NIA) funded Religious Orders Study. Since 1993 more than 1000 persons have agreed to annual clinical evaluations and to donate their brains to the Rush investigators at the time of death.
Study participants took tests of memory, language, attention and other cognitive abilities each year to document their clinical status. The diagnosis of mild cognitive impairment (MCI) was made when impaired performance on these tests was not severe enough to warrant a diagnosis of dementia. After death, the investigators measured the amount of Alzheimer's disease pathology and cerebral infarcts (strokes) through brain autopsy. Of the 37 individuals with MCI, more than half (23) met pathologic criteria for Alzheimer's disease, and nearly a third (12) had cerebral infarcts (this include five with both). Less than a quarter (9) did not have either pathology.
"Because most people with mild cognitive impairment progress to dementia, it has been difficult to obtain brain tissue from persons who die while they still have the condition," said Bennett. "We now know that both clinically and pathologically, mild cognitive impairment patients are in the middle in terms of the disease process for Alzheimer's disease and cerebral vascular disease," said Bennett.
One positive finding from the study is that one-third (60) of the total study participants with an average age of 85 did not experience cognitive decline over several years of follow-up. Yet, about half of these persons had significant Alzheimer's disease pathology and nearly a quarter had cerebral vascular disease. "It is likely that these individuals have some type of 'reserve' capacity in their brains that allows them to escape the loss of memory despite the accumulation of pathology," said Bennett.
Bennett and his colleagues are involved in another NIA funded study at Rush, the Memory and Aging Project, trying to identify what keeps these individuals from becoming impaired. "Preventing the accumulation of disease pathology is a common approach to disease prevention," said Bennett. "Another way to prevent loss of cognition is to identify factors that protect us from becoming forgetful despite this pathology.
"From a public health perspective, the number of people with cognitive loss due to Alzheimer's disease and cerebral vascular disease is probably much larger than current estimates," said Bennett. He hopes that these data provide additional impetus to research efforts to develop treatments and, ultimately, prevention for these common diseases of aging.
On the downside if you live into your 80s the odds of suffering from cognitive declines are very high. Your odds of living into your 80s are going to rise with future advances in biotechnology and biomedical science. So most of us should see this report as describing the likely future of our brains - barring the development of treatments that prevent these diseases.
Treatments for Alzheimer's Disease and for cerebral vascular disease would benefit much larger numbers of people than current estimates of disease incidence would suggest. Therefore the value of developing treatments for these diseases is even greater that previous estimates would lead one to believe. A great increase in biomedical science funding would pay very rich dividends.
You gotta ask yourself: Do you want your brain to rot? Well, do you?
I really hate to say this, but no amount of increase in funding will cure a damn thing. It's throwing money away and raising everyone's taxes.
The system cannot produce what we want. It's really as simple as that. The socialist medical marketplace with the impedance dampeners of FDA/NIH squashes everything flat. Giving the noncreators of the NIH more money [they don't know how to deliver to market] and creating more of a logjam at the joke of the drug-side of the FDA [they just make obstacles] is hardly a solution. Big Pharma certainly doesn't need the dollars. In fact, a little competitive starvation might do them a world of good.
Or put another way, when the first question I'm asked is not "Does it work and work well?" and the second question is not "How does it work?" but instead are "What is the regulatory framework?" and "How long does it take to get through that framework?" you know that the industry can't really produce anything. It's subject to overregulation, permission-by-authority, and non-competitive criteria. Sure signs of inevitable decline and destruction. "Please let me make money .gov? Pretty please..."
Not that Big Pharma can help here.
In a multi-factorial multi-dimensional human system of incredible complexity, Big Pharma thinks that if it finds the right drugs for the right targets all will be well and the billions will flow in. Poppycock. We have been suffering the Silver Bullet myth ever since we crushed infectious disease with antibiotics and that has skewed the thinking. What we need is a deep pyschological change. The average Joe has to demand in the present rapid development of treatments. The average biotech has to demand total deregulation of the medical marketplace. If this doesn't happen, the last 20 years of medical advances (a hill of beans compared to what's needed) will be the next 20 years, amounting again to negligible progress.
Right now, in this very moment, I have in my desk drawer the first pass design/business plan of a wearable, cartridge-based artificial kidney. The reasons it is not in production have ZERO to do with funding. See paragraph above for Silvet Bullet myth. The system is not interested in pursuing it. I could build it and demonstrate it works and watch it go nowhere or fight the Medicare-in-bed-with-dialysis makers war.
"But Bob, that's not true -- build it and they will come." Poppycock again. We have known for ten years that apheresis with an LDL absorbing column will basically reverse peripheral vascular disease as well artherosclerosis in heart and aorta. When was the last time you heard of a 65yr old being treated by LDL apheresis? Use Statins they scream! Or what about high-intensity focused catheter laser-based ablation of clogged arteries? Hasn't that been around at least a decade? Hell even BILL CLINTON had to go off and do bypass surgery - talk about absurdly primitive compared to off-the-shelf available now alternatives. See the problem is pyschological not funding.
So, I'm not a fan of increased funding. Just deregulate. Even if you multiply funding by 10x you aren't going to see anything. There are no real garage biotech entrepreneurs to be the fertile soil from which to spring the cures.
Conversely I'm a big fan of FuturePundit. I think that sites like this are the very dynamic that has a chance to start pushing more and more folks and folks with leverage power towards a more common sense perspective of how to get from here to there.
Well back to the grindstone...
You may or may not be aware that your computer's processor isn't being used anywhere near its full capacity most of the time. This is therefore a waste of the resources which were put into its manufacture and the electricity which powers it.
Instead of this you can install a small program which makes use of your computer's processing power when you're not using it by performing calculations for non-profit medical and scientific research for Stanford University including research into Alzheimers. There are currently over one million CPUs registered. I have personally been using the program for over two years with no problems.
You can find out more and download the program here:
Alternative Energy Blog
I generally agree Robert. However, caloric restriction does seem to indicate that there is a silver bullet for at least some aspects of aging. Anyway, are all other countries equally paralyzed by regulation?
My best guess is that the next twenty years will be more-or-less a repeat of the last 20, which were pretty barren, but not useless. I once had an argument about this with Peter Duesberg and was surprised by how many significant things I came up with, but the basic fact is that life expectancy has grown by about 4 years over the last 20. I don't think any political action taken today will fix the regulatory problems. However, between 20 and 30 years from now Medicare/Medicaid will force a reformation of the current medical system. When that happens there may be an opportunity for real reform. In the meantime, if you have a workable system, why not try to sell it somewhere with less regulation? If people can go to the third world and buy a human kidney, surely they can buy your device.
The rate of advance of biomedical research is accelerating because the underlying technologies used to investigate biological systems increasingly overlap with electronic technologies. The sensors and vessels used to measure and manipulate biological systems are constantly getting smaller and more massively parallel. Therefore I expect the next 20 years to produce orders of magnitude more advances than the last 20 years.
I've made many posts on this phenomenon that you can find in my Biotech Advance Rates archive.
I agree with your position that more government spending in this area is reasonable as it is clearly in the public interest. Right wingers will insist that government bureaucracies can't do anything, but they forget that government funded and led research gave us the computer, the internet, radar, nuclear power (and weapons)...
The basic problem with dementia and aging in general is that once an organism is past it's normal reproductive age, there is no selective pressure to deal with diseases that crop up after than point, so the organism effectively self destructs. So humans who are over 40 or so really are "over the hill". In our ancient biological past the only thing that mattered was reproductive capacity, but in modern societies the old and wise are very valuable and must be preserved if possible (and because I'm a bit over 40). But the mechanisms of aging are biochemical and becoming rather well known and they all have possible solutions. However the problems to be solved are complex and interrelated and the solutions are more long term than industry can normally tolerate, since they necessarily have a short term profit perspective. With the geometric progression of advances in bio-engineering, money spent in these areas has a very high prospect for excellent payoff. And the payoff is real in economic terms. If we can extend the useful working lifespan of the populace five years the so-called crisis in Social Security is over. And the cost of that solution will likely be far less than one year in Iraq and miniscule compared to the (over)estimated cost of $10 trillion for social security repair. Government has a clear role to play in terms of coordinating a broad effort for maximum efficiency. I am convinced that the demographic power of us baby boomers that solved the scourge of acne in the sixties and seventies will take care of the aging problem in the early 21st century.
Yes Randall, I know what you think on this topic, and without a metric one can't ever definitively say one way or another, but with respect to my proposed metric, life expectancy, the previous two decades produced rather similar results, and I see no reason to expect the next one to be very different. The evidence that suggests that the next decade will show acceleration in tech progress existed ten years ago, when it suggested that the decade just past would show acceleration in tech progress. Maybe there was some improvement in the rate of medical tech development in the last decade, and maybe there will be some comparable improvement in the next decade, but it is blindingly obvious to me that there has not been anything like the magnitude of improvement that one would expect from a naive model relating research inputs to outputs, which strongly supports, in my opinion, the position that we know little about how scientific inputs lead to outputs, and thus know little about how to encourage, or "buy" scientific progress.
The model of technological development exemplified by Ray Kurzweil's predictions from "Age of Spiritual Machines" and elsewhere, by De Solla Price's "Big Science, Little Science" and by the Civilization computer game has empirically failed to make accurate predictions suggesting the need for a new model.
By the way, I'm not saying aging can't be beaten, just that it won't be beaten by more of the same. We already have more of the same, and still more and still more of the same relative to 50 years ago, but progress, while respectible, is no-where near promise.
I am reminded of the computer industry in the 1970s compared to the computer industry in the 1950s. Yes, it looked much the same. No, it was not going to continue to look the same. Suddenly semiconductors became fast and small and cheap enough that desktop computers became feasible. A critical mass was reached.
I see the same thing happening in biotech. Gene arrays have increased their density by orders of magnitude in the last 10 years. DNA sequencing costs have fallen by orders of magnitude. SNP testing costs have fallen by orders of magnitude. We are reaching turning points that are analogous to the birth of the desktop PC. For example, I am expecting microfluidics technologies to come into widespread use in the next 5 years.
In my earlier post I made the statement that "the cost of that solution (extending the useful working lives of seniors) will likely be far less than one year in Iraq and miniscule compared to the (over)estimated cost of $10 trillion for social security repair."
Looking at pharmaceudical industry numbers strongly supports that contention, I think.
http://www.phrma.org/whoweare/presscorner/06.02.2004.906.cfm indicates that the total spending for all private sector drug research is $30 billion/year. If roughly a third of that is spent on relevant geriatric research, one year in Iraq, about $100 billion, would pay for doubling the geriatric drug research for ten years. Of course you can't simply throw money at problems like these, there is a limit to how much the current research establishment can effectively absorb, but a very substantial government/private sector partnership program could be undertaken. It is worth noting that the total time for the Manhatten project was three years. Unfortunately saving lives and improving them is never quite as exciting as the appeal of weapons of mass destruction, real or imagined.
Thank you for putting the information on the web I have an assignment on this subject and it was helpful. Please email me so more information for my record or keep in touch as its a four year degree course.
Robert Silvetz long posting shows he's been around a while and what he's observed makes him lose confidence in the present system. But his remedy -- deregulation -- is presented as an article of faith. We should trust an unregulated pharmaceutical industry when a regulated one produced so many medications that had to be pulled off the market? I guess he might argue that the number of deaths and illnesses resulting from an unregulated industry would be fewer than the present system. I'd be interested in seeing any evidence to support this. If I did, I'd sign up.