Secrets of Aging

What does a normally aging brain look like? Are diseases of aging such as Alzheimer’s inevitable?

By | September 1, 2011

CORBIS, OWAKI/KULLA

Only 40 years ago it was widely believed that if you lived long enough, you would eventually experience serious cognitive decline, particularly with respect to memory. The implication was that achieving an advanced age was effectively equivalent to becoming senile—a word that implies mental defects or illness. As a graduate student back then, I was curious why such conclusions were being drawn about the elderly. I had only to look as far as my own great-grandmother and great-aunt to begin questioning the generalization. They lived to 102 and 93, respectively, and were exceptionally active and quick-witted enough to keep us twentysomethings on our toes. A closer look at the literature didn’t give me any confidence that either the biological basis of memory or how it might change with age was well understood. Many discoveries made in the years since have given us better tools to study memory storage, resulting in a major shift away from the view of “aging as a disease” and towards the view of “aging as a risk factor” for neurological diseases. So why do some people age gracefully, exhibiting relatively minor—and at worst annoying—cognitive changes, while others manifest significant and disabling memory decline? Answers to these questions are fundamental for understanding both how to prevent disease and how to promote quality of life.

A test for normal aging

Cognitive decline at older ages is marked by gradual loss in the ability to retain new information or to recall the past. Although many other changes occur during the aging process—impairment in range of motion, speed of gait, acuity of vision and hearing—none of these factors are as central to one’s personal identity as are one’s cumulative experiences. For me, it seemed that understanding memory, and how it changes with age or disease, was the key to understanding the aging brain.

Infographic: Molecular Learning View full size JPG | PDF
Infographic: Molecular Learning
View full size JPG | PDF
TAMI TOLPA

When I was in graduate school, in 1973, two papers came out that would change the shape of neuroscience and memory research. Terje Lømo, Tim Bliss, and Tony Gardner-Medwin devised a method that could experimentally alter synaptic strength. Earlier theoretical ideas had implied that strengthening the connection between neurons might explain how memories were formed: the stronger the connection, the better a message could be relayed or recalled. As electrophysiologists, Lømo and colleagues tested this idea by sending electrical currents through a group of neurons in the rabbit hippocampus in patterns that mimicked normal electrical activity, and measuring how the connections between the neurons changed. By stimulating neurons, they could create a durable increase in synaptic strength, which was later dubbed long-term potentiation, or LTP. But more than just an intriguing physiological observation, the research presented a fully controllable experimental proxy for learning that made it possible to study memory across the lifespan of an animal for the first time.

Thus, with the discovery of LTP, and the idea that animal models of human memory could be developed, I sought to finish my dissertation research in a lab that was routinely conducting LTP experiments. At the time, there were only three labs in the world that were doing these types of experiments: Graham Goddard’s laboratory at Dalhousie University, Tim Bliss’s at University College London, and Gary Lynch’s at UC, Irvine. As it turned out, my thesis advisor Peter Fried, at Carleton University in Ottawa, had been one of Goddard’s students, and introduced me to him by saying, “I don’t really want you to steal my student, but she has this idea that she thinks you might be interested in.” I explained to Goddard that I wanted to track an animal’s ability to make and keep spatial memories as it aged. Since the hippocampus—the area of the brain where LTP was first discovered—was also involved in spatial memory, I wanted to use Goddard’s setup and surgically implant electrodes that could measure LTP in awake, freely behaving rats. In an act of faith and generosity, Goddard soon purchased animals for me and began to “age” them in anticipation of my arrival the following year.

The behavioral tests used to study spatial memory at this time all used somewhat severe methods to motivate animals: either with shock—a significant stress—or by restricting eating or drinking, both of which were potentially detrimental to survival. Because the precious aged animals could not be replaced without waiting two years to grow another “old” batch, I developed a novel, milder task that is now often referred to as the Barnes maze. With rodents’ natural aversion to open, well-lit areas in mind, I designed a circular platform with many openings around its circumference, only one of which would allow the animal to escape into a dark box beneath the platform’s surface.

Aging is not equivalent to the aberrant process of Alzheimer’s disease; it is in fact a distinctly different neurological process.

At 2–3 years old (an age equivalent to about 70-80 human years), the rats were old enough to begin the behavior and electrophysiological experiments in the latter part of 1975. The animals were permanently implanted with electrodes that could both stimulate the neurons and record their activity. The electrodes allowed us to measure baseline synaptic transmission with single stimuli, then to induce LTP, and finally to monitor its decay over several weeks. We found that LTP decayed about twice as fast in the old rats as it did in the young, with the “synaptic memory” lasting 20 days rather than 40. Most importantly, the durability of LTP was correlated with the memory of the correct hole on the circular platform task. In fact, by combining behavior and electrophysiology techniques, we produced the first demonstration that instead of acting as a mere proxy for learning, LTP might actually represent the cellular mechanism by which all memories are created.[1. C. A. Barnes, "Memory deficits associated with senescence: A neuro-physiological and behavioral study in the rat," J Comp Physiol Psychol, 93:74-104, 1979.]

Just one year before I published my work on aging rats, Bruce McNaughton, then at Dalhousie University, demonstrated that for synaptic strengthening to occur, synapses from several neurons needed to converge and be coactive on the target neuron. The finding made perfect sense, since learning often comes from the association of two or more pieces of information, each of which could be carried by an individual neuron. Later experiments also demonstrated that under some conditions, LTP can be more difficult to induce in aged rats, and conversely, that a reduction in synaptic strength—called long-term depression or LTD—is easier to induce in the hippocampus of old rats.[2. C. Norris et al., "Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging," J Neurosci, 16:5382-92, 1996.] This may mean that LTD participates in “erasing” LTP, or reducing its longevity, and thus possibly increases forgetting.

By the mid-1980s it was clear that even in normal aging there are subtle changes in the biological processes that underlie memory, and in the relationship between the strength of memory and the strength of the synapses. But the real message of these experiments was that old animals can and do learn. None of the older animals exhibited what could be considered behaviorally to be “dementia,” nor were their biological mechanisms that allow memory traces to be laid down completely dysfunctional.

Aging networks

While there is much to be learned about the physiology of neural systems by direct artificial stimulation, even the mildest currents do not exactly mimic the selective and distributed activity of cells in normal behavioral states. To more realistically understand the aging brain, it is necessary to monitor cell circuits driven by natural behaviors. Around the time that LTP was discovered, John O’Keefe at University College London discovered “place cells” in the hippocampus—a major breakthrough for the field. By simply placing small microwires very close to hippocampal cells, without stimulating them, John and his student Jonathan Dostrovski noted that individual hippocampal cells discharge action potentials only when a rat is at select physical locations as it traverses a given environment.[3. J. O'Keefe, J. Dostrovsky, "The hippocampus as a spatial map: Preliminary evidence from unit activity in the freely-moving rat," Brain Res, 34:171-75, 1971.] The unique property of these place cells is that their “receptive fields,” or the features that make each of these cells fire, are related to specific regions of space.

Infographic: Lost in Space View full size JPG | PDF
Infographic: Lost in Space
View full size JPG | PDF
TAMI TOLPA (MAZE); CAROL BARNES (COGNITIVE MAP, SOURCE: NATURE 388/ 17 JULY 1997)

By recording from many individual place cells at once, using a multipronged electrode (the tetrode) developed by McNaughton, and determining which physical locations activated different cells in the brain, it was possible to visualize how the hippocampus constructs a “cognitive map” of the surroundings. If young rats were given one maze-running session in the morning, and another session in the afternoon, the same hippocampal map was retrieved at both time points—suggesting that the pattern of neuronal firing represented the memory of their walking through the rectangular, figure-eight maze. What surprised us was that about 30 percent of the time, when old rats went back for their second run of the day, a different place-cell distribution would appear—as if the older animals were retrieving the wrong hippocampal map.[4. C. Barnes et al., "Multistability of cognitive maps in the hippocampus of old rats," Nature, 388:272-75, 1997.] Certainly a rat navigating a familiar space with the wrong map is likely to appear lost, or as though it had forgotten its way. But why was the rat retrieving the wrong map?

The possible answer to this question was published in 1998 by Cliff Kentros, now at the University of Oregon. In young rats, Cliff pharmacologically blocked the NMDA receptor, a critical gateway regulating LTP and synaptic strengthening. When he and colleagues used a dose large enough to block the formation of LTP, the cognitive maps of the young rats began to degrade over time in much the same way as observed in aged rats, suggesting that faulty LTP mechanisms may be responsible for map instability in aging.[5. C. Kentros et al., "Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade," Science, 280:2121-26, 1998.]

Connecting the hippocampal dots

Even though the new multiple tetrode recording method was a large advance over the limitations of recording one or two neurons at a time, these methods were still constrained to sample sizes of ~100 to 200 cells.

One recent advance has allowed us to monitor cell activity on a broader scale, not with electrodes, but by tracking the expression of genes that are rapidly expressed during behavior. Monitoring the expression of one such gene, Arc, during behavioral tests, for example, John Guzowski in my lab developed a method that could report on activity over hundreds of thousands of cells across the brain (the ‘catFISH’ method).[6. J.F. Guzowski et al., "Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles," Nat Neurosci, 2:1120-24, 1999.] This large-scale imaging of single cells has been critical for identifying which cells, within which memory circuits, are altered during normal aging.

This technique also allowed us to tease apart which cells might be more susceptible to decline with age. Unlike electrodes that record LTP, which cannot differentiate between different types of neurons, the catFISH method allows us to distinguish between the three primary cell groups within the hippocampus—the granule cells of the dentate gyrus and the pyramidal cells of regions CA1 and CA3. We were able to show that cell-specific gene expression (and therefore cell activity) did not change with age in CA1 and CA3 cell regions, but that the number of granule cells engaged during behavior showed a continuous decline in aging rats, suggesting these cells are a weak link in the aging rat hippocampus.[7. S.A. Small et al., "Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging," PNAS, 101:7181-86, 2004.] Could this also be true in primates?

Scott Small at Columbia University Medical Center helped me answer this question in young and old monkeys. Although MRI methods do not have single-cell resolution, they can provide an indirect gauge of activity over large segments of the brain. Using a variation of standard MRI that measures regional cerebral blood volume (CBV), we monitored the resting brain activity of monkeys ranging in age from 9 to 27 years (equivalent to 27 to 87 human years), and could then relate this brain activation to an individual animal’s performance in memory tests. There were no differences in resting metabolic measures in the areas of the brain that send most of the signals into or out of the hippocampus, nor were there differences in brain activity within CA1 or CA3. But the old monkeys did show reduced activity in the dentate gyrus, similar to what we had found in aging rats. Critically, we observed that the lower the activity in the dentate gyrus, the poorer the memory.7

Scott had observed a similar pattern in an earlier human aging study. However, with human studies there is always a concern that some of the people we assume are aging normally in fact have the undiagnosed beginnings of human-specific neurological disease, such as Alzheimer’s. Confirming the observation in aging animals, which do not spontaneously get this disease, provides strong evidence that the dentate gyrus is a major player in the changes that occur in normally aging mammals.

Furthermore, these data refute the contention that aging is effectively equivalent to an aberrant process like Alzheimer’s disease, revealing that it is in fact a distinctly different neurological process. In contrast to the results showing that aging primarily affects the dentate gyrus, the granule cells of this brain region in Alzheimer’s patients do not show changes (with respect to age-matched controls) until very late in the illness. Instead, it is the cells in CA1 and in the entorhinal cortex that are dramatically affected. Thus, while aging and Alzheimer’s may in some cases be “superimposed,” there is not a simple linear trajectory that leads us all to end up with the disease.

Memory genes

Infographic: The Seat of Memory View full size JPG | PDF
Infographic: The Seat of Memory
View full size JPG | PDF
TAMI TOLPA

Presently, the omics revolution is leading us closer to an understanding of individual differences in aging and cognition. One example with respect to memory is a study that used a genome-wide association approach in 351 young adults to identify the single nucleotide polymorphisms (SNPs) most strongly related to memory. The most significant SNP identified was a simple nucleotide base change in the normal cytosine-thymine sequence at a specific location in the KIBRA gene, which encodes a neural protein that had been suspected of playing a role in memory. Those who had the thymine-thymine SNP had the best memories.[8. A. Papassotiropoulos et al., "Common Kibra alleles are associated with human memory performance," Science, 314:475-78, 2006.] This was further confirmed in an independent elderly population,[9. K. Schaper et al., "KIBRA gene variants are associated with episodic memory in healthy elderly," Neurobiol Aging, 29:1123-25, 2008.] supporting the view that this particular SNP in the KIBRA gene predisposed people of any age to have “better memory.” This could be another clue to help guide our understanding of the molecular cascades that support good memory, as the activity of the KIBRA protein may influence mechanisms related to LTP. Could there be a link between KIBRA and age-related memory decline? One way to test this hypothesis was to find a way to manipulate part of the molecular circuit in which KIBRA is involved. Performing just such an experiment in collaboration with my lab, Matt Huentelman at the Translational Genomics Research Institute in Arizona identified a promising compound, hydroxyfasudil, a metabolite of a drug already approved for use in treatment of chest pain, or angina. As predicted, hydroxyfasudil improved spatial learning and working memory in aged rats.[10. M.J. Huentelman et al., "Peripheral delivery of a ROCK inhibitor improves learning and working memory," Behav Neurosci, 123:218-23, 2009.] The clinical applications of the drug’s effects on learning and memory are currently being explored.

David Sweatt at the University of Alabama at Birmingham also recently documented DNA methylation changes in response to learning, and was very interested in collaborating with us to determine whether changes in this epigenetic process during aging might explain our data on Arc expression, which is related to LTP formation and learning. Methylation of DNA typically downregulates transcription. After young and old rats performed exploratory behaviors that engaged the hippocampus, the methylation state of the Arc gene in hippocampal cells was, in fact, reduced in both age groups (which allowed more of the Arc mRNA to be transcribed). The difference between young and old animals was that certain cells of older animals, such as hippocampal granule cells, had higher overall methylation levels in the resting state, which resulted in production of less Arc protein during behavior, and the diminished ability to alter synapses via a mechanism such as LTP.[11. M.R. Penner et al., "Age-related changes in Arc transcription and DNA methylation within the hippocampus," Neurobiol Aging, doi: 10.1016/j.neurobiolaging.2010.01.009] There are many complex facets of these data, but the results have led us and others to hypothesize that there may well be a number of epigenetic marks that accumulate during aging, and that epigenetic dysregulation may be a fundamental contributor to normal age-related cognitive decline. While the details of exactly how aging affects epigenetic modifications remain to be elucidated, it is at least a reasonable guess that understanding these mechanisms will be critical for future experimental designs aimed at optimizing cognition across the life span. Luckily, these processes are also amenable to pharmacological manipulation.

Aging in the future

Looking back on the rather grim expectations concerning memory and the elderly that were held only a few decades ago, the vision today is very different and much more positive. There are many who live to very old ages with minimal cognitive decline—and certainly no dementia. One particularly interesting study in this regard followed individuals who were 100 years of age (centenarians) at the beginning of the study until the time of their death, monitoring cognitive function and other factors in the “oldest old.” Interestingly, 73 percent of these centenarians were dementia free at the end of their lives (the oldest reaching an age of 111 years).[12. B. Hagberg, G. Samuelsson, "Survival after 100 years of age: a multivariate model of exceptional survival in Swedish centenarians," J Gerontol A Biol Sci Med Sci, 63:1219-26, 2008.] Watching the remarkable discoveries in biology over the past half century, one cannot help but look with excitement towards the next groundbreaking findings that are surely in the making. The future holds great promise for the once remote dream of understanding the core biological processes required for optimal cognitive health during aging—and progress in this regard should also provide the needed backdrop for understanding and preventing the complex neurological diseases that can be superimposed on the aging brain.

Carol Barnes is Director of the Evelyn F. McKnight Brain Institute and a Regents’ Professor of Psychology and Neurology at the University of Arizona.

This article is adapted from an upcoming review in F1000 Biology Reports. It will be available for citation at f1000.com/reports (open access).

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Avatar of: AgingScientist

Anonymous

September 7, 2011

I will ask the unacceptable question.  Why this drive for investing in aging research?  Most say it's so we can remain healthy as we age.  Let's not kid ourselves: we want to live LONGER...and healthy.  Is living longer a good thing? I'm not sure. It needs to be discussed.  Right now we all insist on curing every problem of aging--heart disease, cancer, Alzheimers...-- which automatically makes us live longer.  We're avoiding the main issue.  Perhaps living to age 68 and dying is a good thing.  Why is 78 or 98 better? No "Soylent Green", but a serious discussion of what we should spend our resources and efforts on.

Avatar of: Patrick Danahy

Anonymous

September 7, 2011

Clear, balanced, beautifully written, strong enough to support the optimistic outlook. Thanks!

Avatar of: Dekama20

Anonymous

September 7, 2011

Very interesting,and sensible,as I myself,am 82,and feeling I do have a sharper in and outlook and a "strong memory."
Cap.(MM0R.W.de Jong

Avatar of: anonymous eib

Anonymous

September 7, 2011

How refreshing to see an article in The Scientist that is written by a scientist who really knows what she's talking about!  Thank you. 

Avatar of: captainhurt

captainhurt

Posts: 2

September 7, 2011

by definition, AGING IS A DISEASE!
disease: "A pathological condition of a part, organ, or system of an organism resulting from various causes"

this author reveals some interesting studies, but all these little studies and university experiments ultimately are not coordinated and have no universal mission, other than to gain authors' notoriety and attempt to justify more $$ for little professor led study grants ad infinitum.

Avatar of:

Posts: 0

September 7, 2011

I will ask the unacceptable question.  Why this drive for investing in aging research?  Most say it's so we can remain healthy as we age.  Let's not kid ourselves: we want to live LONGER...and healthy.  Is living longer a good thing? I'm not sure. It needs to be discussed.  Right now we all insist on curing every problem of aging--heart disease, cancer, Alzheimers...-- which automatically makes us live longer.  We're avoiding the main issue.  Perhaps living to age 68 and dying is a good thing.  Why is 78 or 98 better? No "Soylent Green", but a serious discussion of what we should spend our resources and efforts on.

Avatar of:

Posts: 0

September 7, 2011

Clear, balanced, beautifully written, strong enough to support the optimistic outlook. Thanks!

Avatar of:

Posts: 0

September 7, 2011

Very interesting,and sensible,as I myself,am 82,and feeling I do have a sharper in and outlook and a "strong memory."
Cap.(MM0R.W.de Jong

Avatar of:

Posts: 0

September 7, 2011

How refreshing to see an article in The Scientist that is written by a scientist who really knows what she's talking about!  Thank you. 

Avatar of:

Posts: 0

September 7, 2011

by definition, AGING IS A DISEASE!
disease: "A pathological condition of a part, organ, or system of an organism resulting from various causes"

this author reveals some interesting studies, but all these little studies and university experiments ultimately are not coordinated and have no universal mission, other than to gain authors' notoriety and attempt to justify more $$ for little professor led study grants ad infinitum.

Avatar of:

Posts: 0

September 7, 2011

I will ask the unacceptable question.  Why this drive for investing in aging research?  Most say it's so we can remain healthy as we age.  Let's not kid ourselves: we want to live LONGER...and healthy.  Is living longer a good thing? I'm not sure. It needs to be discussed.  Right now we all insist on curing every problem of aging--heart disease, cancer, Alzheimers...-- which automatically makes us live longer.  We're avoiding the main issue.  Perhaps living to age 68 and dying is a good thing.  Why is 78 or 98 better? No "Soylent Green", but a serious discussion of what we should spend our resources and efforts on.

Avatar of:

Posts: 0

September 7, 2011

Clear, balanced, beautifully written, strong enough to support the optimistic outlook. Thanks!

Avatar of:

Posts: 0

September 7, 2011

Very interesting,and sensible,as I myself,am 82,and feeling I do have a sharper in and outlook and a "strong memory."
Cap.(MM0R.W.de Jong

Avatar of:

Posts: 0

September 7, 2011

How refreshing to see an article in The Scientist that is written by a scientist who really knows what she's talking about!  Thank you. 

Avatar of:

Posts: 0

September 7, 2011

by definition, AGING IS A DISEASE!
disease: "A pathological condition of a part, organ, or system of an organism resulting from various causes"

this author reveals some interesting studies, but all these little studies and university experiments ultimately are not coordinated and have no universal mission, other than to gain authors' notoriety and attempt to justify more $$ for little professor led study grants ad infinitum.

Avatar of:

Posts: 0

September 11, 2011

Thank you for a very interesting article; I learnt from it eventhough my field was theorectical physics (and now computers.)

Avatar of:

Posts: 0

September 11, 2011

Thank you for a very interesting article; I learnt from it eventhough my field was theorectical physics (and now computers.)

Avatar of: Babak Makkinejad

Anonymous

September 11, 2011

Thank you for a very interesting article; I learnt from it eventhough my field was theorectical physics (and now computers.)

Avatar of: pass it on

Anonymous

September 12, 2011

You have touched the crux, yes - a discussion is in order. Wouldn't it be nice if science could optimize our health, so that each of us could exist with our memories and bodies intact until - poof!  we suddenly and painlessly evaporate, leaving space on the planet and the good works of life to those who follow?

Avatar of:

Posts: 0

September 12, 2011

You have touched the crux, yes - a discussion is in order. Wouldn't it be nice if science could optimize our health, so that each of us could exist with our memories and bodies intact until - poof!  we suddenly and painlessly evaporate, leaving space on the planet and the good works of life to those who follow?

Avatar of:

Posts: 0

September 12, 2011

You have touched the crux, yes - a discussion is in order. Wouldn't it be nice if science could optimize our health, so that each of us could exist with our memories and bodies intact until - poof!  we suddenly and painlessly evaporate, leaving space on the planet and the good works of life to those who follow?

Avatar of:

Posts: 0

September 13, 2011

How old are you?

Avatar of:

Posts: 0

September 13, 2011

Existing for most is vast preferable than the alternative.   Is living longer a good thing?  The question is as ridiculous as it illogical.  Of course living longer is a good thing.  There are certainly situations where an individual may wish to no longer experience the physical or psychic suffering associated with being alive, but the ability to contribute anything of value to this world is predicated on being alive in the first place.  When people start talking about what "we" should do and what limits "we" should allow on medical treatment of the suffering and benefit of others, I begin to get very uncomfortable.  The only serious discussion that should be undertaken is how quickly "we" can save as many lives as possible to allow them to live to continue to contribute to their families and communities.

Avatar of:

Posts: 0

September 13, 2011

Agree.  The story of cognitive decline is in the epigenetics - environment social, as well as physical and biological, affecting gene expression.  My mother 99 has little if any signs of cognitive decline - the little has to do with remembing names of her clients who a few years ago were readily forthcoming in her daily discourse. 

Avatar of:

Posts: 0

September 13, 2011

Agree.  The story of cognitive decline is in the epigenetics - environment social, as well as physical and biological, affecting gene expression.  My mother 99 has little if any signs of cognitive decline - the little has to do with remembing names of her clients who a few years ago were readily forthcoming in her daily discourse. 

Avatar of:

Posts: 0

September 13, 2011

If one looks at Boyd Haley's research (ex-Chair of Chemistry, Kentucky Univ, Lexington) another valid reason appears. Current and previous centenarians did not have numerous dental amalgam fillings where mercury vapour continuously destroys B-tubulin in the brain. Following Haley's advice, Apo-E genotyping a recognised risk factor for senile dementia of Alzheimer's type was investigated (Godfrey et al J.Alz.Dis. 2003) and confirmed that memory loss was associated with a genetically impaired ability to eliminate mercury. We are now facing the legacy of post WW2 gluttony combined with socialised dentistry believing that mercury combined with silver, tin, zinc and copper, and bathed in hot salty acidic saliva will not corrode.
Mike Godfrey

Avatar of:

Posts: 0

September 13, 2011

How old are you?

Avatar of:

Posts: 0

September 13, 2011

Existing for most is vast preferable than the alternative.   Is living longer a good thing?  The question is as ridiculous as it illogical.  Of course living longer is a good thing.  There are certainly situations where an individual may wish to no longer experience the physical or psychic suffering associated with being alive, but the ability to contribute anything of value to this world is predicated on being alive in the first place.  When people start talking about what "we" should do and what limits "we" should allow on medical treatment of the suffering and benefit of others, I begin to get very uncomfortable.  The only serious discussion that should be undertaken is how quickly "we" can save as many lives as possible to allow them to live to continue to contribute to their families and communities.

Avatar of: Mike Godfrey

Anonymous

September 13, 2011

If one looks at Boyd Haley's research (ex-Chair of Chemistry, Kentucky Univ, Lexington) another valid reason appears. Current and previous centenarians did not have numerous dental amalgam fillings where mercury vapour continuously destroys B-tubulin in the brain. Following Haley's advice, Apo-E genotyping a recognised risk factor for senile dementia of Alzheimer's type was investigated (Godfrey et al J.Alz.Dis. 2003) and confirmed that memory loss was associated with a genetically impaired ability to eliminate mercury. We are now facing the legacy of post WW2 gluttony combined with socialised dentistry believing that mercury combined with silver, tin, zinc and copper, and bathed in hot salty acidic saliva will not corrode.
Mike Godfrey

Avatar of: Youngman

Anonymous

September 13, 2011

How old are you?

Avatar of: caerus_pounces

caerus_pounces

Posts: 2

September 13, 2011

Existing for most is vast preferable than the alternative.   Is living longer a good thing?  The question is as ridiculous as it illogical.  Of course living longer is a good thing.  There are certainly situations where an individual may wish to no longer experience the physical or psychic suffering associated with being alive, but the ability to contribute anything of value to this world is predicated on being alive in the first place.  When people start talking about what "we" should do and what limits "we" should allow on medical treatment of the suffering and benefit of others, I begin to get very uncomfortable.  The only serious discussion that should be undertaken is how quickly "we" can save as many lives as possible to allow them to live to continue to contribute to their families and communities.

Avatar of: Lloyd Sherman

Anonymous

September 13, 2011

Agree.  The story of cognitive decline is in the epigenetics - environment social, as well as physical and biological, affecting gene expression.  My mother 99 has little if any signs of cognitive decline - the little has to do with remembing names of her clients who a few years ago were readily forthcoming in her daily discourse. 

Avatar of:

Posts: 0

September 13, 2011

If one looks at Boyd Haley's research (ex-Chair of Chemistry, Kentucky Univ, Lexington) another valid reason appears. Current and previous centenarians did not have numerous dental amalgam fillings where mercury vapour continuously destroys B-tubulin in the brain. Following Haley's advice, Apo-E genotyping a recognised risk factor for senile dementia of Alzheimer's type was investigated (Godfrey et al J.Alz.Dis. 2003) and confirmed that memory loss was associated with a genetically impaired ability to eliminate mercury. We are now facing the legacy of post WW2 gluttony combined with socialised dentistry believing that mercury combined with silver, tin, zinc and copper, and bathed in hot salty acidic saliva will not corrode.
Mike Godfrey

Avatar of:

Posts: 0

September 14, 2011

This is very interesting and valuable. It seems human can keep the memory forever. I have built a human brain over Internet, and it seems able to conduct what I want it to. e.g. I can make any home sold in a day or two. It sounds like magic, but it is not because human brain all interconnected. In any case, my Internet brain also suffer "mercury" type of damaging, so the memory kept loosing, here and there. Your posting reminds me to check out what it the equivalent "mercury" in my Internet Brain.

Avatar of:

Posts: 0

September 14, 2011

Do we have the right to live that long ? Good wits and diapers included?
Capable to atribute to mankind-- bullsh..! Procreation capability has degenerated so the inborn feroucious wish to go on...like greatgrandma prepairing breakfast for greatgrandchildren ...till what age she should be permitted....? Wrinckels look prozaic..but when you have turned a pain in the ass ....your brain is not good enough to consider that question... do you have the right to live that long?
How old grew Mr Altzheimer? Anybody rembers..?

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Posts: 0

September 14, 2011

This is really very funny ,I like it very much ,Thank you for the post !I would also like to share you with some good ideas about HP Pavilion G60 battery.

Avatar of: Cheng

Anonymous

September 14, 2011

She must not have browsed Internet too much. If one browses Internet so much and so powerful (e.g. like myself with hundreds of windows and tabs open, pop up, swap, ...etc. your brain will got too much and all interconnected to each other, yet you can NOT use your mouth to describe. It is like a binary code with no source code).

Avatar of: Cheng

Anonymous

September 14, 2011

You may want to add "psychology", "nuroscience" to your field, basically, Pshchology is the learning of "human software" and Nuroscience is "human hardware", in particular the brain hardware.

Avatar of: Cheng

Anonymous

September 14, 2011

True or False, depending on how much knowledge you got to understand this wonderful article. First, you got to know Finite Automata and Formal Language well enough to appreciate this finding. Second, this article gives me a thought of building "Extra Hippocampus", in other words, one does NOT always count on its own brain and memory. Like people after seizure often forgot many things, but with help of iPhone to continually taking photos every now and then, those photos can help recover memory after seizure. So, you are talking about if it is the "hardware" damage of the aging brain or the "software problem". In the article, apparently, the alzheimer is "hardware damage", i.e. CA1 and the other cortex, like if your computer hard disk damage, you can not retrieve info. However, the article also prove that it is NOT "hardware" damage for many aging, the CA1 and CA3 not change, but the Dentate Syrup and the responsive. It is like, when you open too many windows or tabs in your browsers, you got slower response, but all the hardware have NO problem. So, to increase the speed or response, just simply kill some windows or close some tabs, and the speed regain. In that regard, isn't that aging brain easy to fix? A young mind is like a new computer or a newly hire to start a browser, few windows open and few tabs open too, so the response is fast, yet the more experience employees may end up have lots of windows and tabs open, and became slow. You can deem this is also "aging". But, neither has "hardware" problem. So, when you talk about "disease", you need to distinguish whether it is "hardware" or "software" problem. Aging could result either or both, and if it is NOT hardware problem, it often can be easily fix, if you know the bug. If it is hardware problem, you want to see if you can find the parts for replacement, otherwise, it is gone forever.

Avatar of: Cheng

Anonymous

September 14, 2011

Before you start losing your memory, I suggest that you take many photos with your iPhone or the like, and write many blogs to document many things that will someday always "supplement" your memory. Human memory is like "capacitor charging", you charge once and it may die away along time, but if you charge it back frequent enough, it will be fresh. On the other hand, when you have so many memory to charge (i.e. aging brain), you will NOT have enough time cycle to do so. So, an auxiliary memory always help a lot!

Avatar of: Dpsummers

Anonymous

September 14, 2011

Aging provides the fruits of age in the products of knowledge, experience and wisdom. To ask why we should spend out resources and efforts in order to prolong prolonging life is answered in the gift that we pass on with all the above to our own and civilization's creative treasure.  

Avatar of: Cheng

Anonymous

September 14, 2011

You should talk to Dr. Jyh who got Ph.D from Columbia Univ and just passed 80 year old. Why? He always believe he can live up to 120 years old, so I introduced Prof Kan to him, who believe he can live up to 150 years old, and the trick is to live LONG enough to catch the medical advance to extend human life. Every Sping Dr. Jyh will come back from Key West FL to Edison NJ, and in Fall, he went back to Key West FL because he believe the cold temperature will shorter his life, same as hot temperature. So, he end up live like birds. In current economy situation, everyone like Dr. Jyh because wherever he goes, he spend. e.g. He would rent a place at Key West FL for $700 a month, month to month, where most units were vacant, and he would rent a furnished room in Edison NJ when Rutgers University students went back home in summer. He would buy a new computer and sold his Toyota Corolla 96 to someone desperately needed in Key West FL. He would go visit many doctors and do check up in whichever hospital with new technology to make sure he is healthy all the time, and therefore, they all make money. Dr. Jyh was very proud to say once he stayed in a hospital for check up, for those days, many vacant beds, the hospital counted on his business. He said he also sent $300 to his sister in San Francisco every month to help her, and, therefore, help the economy of California. Soon, he is going to leave Edison NJ and fly to San Diego CA to visit his 2nd son, he said he wanted to help economy in CA. So, you know if Dr Jyh can live up to 120 years old, he is going to be able to help the economy a lot by continue spending money. My neighbor Sail is also close to 80 year old, and he just bought a brand new car, i.e. created a full time job. He also got his driveway redone, dozen workers came working a whole week, now so new so shine. Then, he decided he got more money than can live long enough, so he got workers to wash his houses every year, and have landscapers to mow the lawn and plant trees, ...etc. Then he took his grandchildren to Chuck E Cheese, to many museums ...etc. Again, helping the economy a lot! If they have died in 68, then, the economy may have been even worse. How about Warren Buffett? or Bill Gates? If they can live up to 120 years old or even 150 years old, then the economy may be much better than if they die earlier, right? Look at Steve Jobs, he may died well before 68 year old, and Apple stocks may collapse, and billions wealth may disappear...

Avatar of: Aging Optimist

Anonymous

September 14, 2011

"Unaccepatable question"? Not sure there are any...AND I am betting you are not 67!  I for one wish to live as long, healthy and productive life as possible.  Can't understand why anyone wouldn't want to; but then we as individuals have the option to end it any time.  I am much, much more disturbed by folks who want to inflict their personal opinions/values on the rest of us...
 I will second Kevin Perrott's post!

Avatar of: Cheng

Anonymous

September 14, 2011

This is very interesting and valuable. It seems human can keep the memory forever. I have built a human brain over Internet, and it seems able to conduct what I want it to. e.g. I can make any home sold in a day or two. It sounds like magic, but it is not because human brain all interconnected. In any case, my Internet brain also suffer "mercury" type of damaging, so the memory kept loosing, here and there. Your posting reminds me to check out what it the equivalent "mercury" in my Internet Brain.

Avatar of: Carolus138

Anonymous

September 14, 2011

Do we have the right to live that long ? Good wits and diapers included?
Capable to atribute to mankind-- bullsh..! Procreation capability has degenerated so the inborn feroucious wish to go on...like greatgrandma prepairing breakfast for greatgrandchildren ...till what age she should be permitted....? Wrinckels look prozaic..but when you have turned a pain in the ass ....your brain is not good enough to consider that question... do you have the right to live that long?
How old grew Mr Altzheimer? Anybody rembers..?

Avatar of: songfangsarah

songfangsarah

Posts: 2

September 14, 2011

This is really very funny ,I like it very much ,Thank you for the post !I would also like to share you with some good ideas about HP Pavilion G60 battery.

Avatar of:

Posts: 0

September 14, 2011

Aging provides the fruits of age in the products of knowledge, experience and wisdom. To ask why we should spend out resources and efforts in order to prolong prolonging life is answered in the gift that we pass on with all the above to our own and civilization's creative treasure.  

Avatar of:

Posts: 0

September 14, 2011

You should talk to Dr. Jyh who got Ph.D from Columbia Univ and just passed 80 year old. Why? He always believe he can live up to 120 years old, so I introduced Prof Kan to him, who believe he can live up to 150 years old, and the trick is to live LONG enough to catch the medical advance to extend human life. Every Sping Dr. Jyh will come back from Key West FL to Edison NJ, and in Fall, he went back to Key West FL because he believe the cold temperature will shorter his life, same as hot temperature. So, he end up live like birds. In current economy situation, everyone like Dr. Jyh because wherever he goes, he spend. e.g. He would rent a place at Key West FL for $700 a month, month to month, where most units were vacant, and he would rent a furnished room in Edison NJ when Rutgers University students went back home in summer. He would buy a new computer and sold his Toyota Corolla 96 to someone desperately needed in Key West FL. He would go visit many doctors and do check up in whichever hospital with new technology to make sure he is healthy all the time, and therefore, they all make money. Dr. Jyh was very proud to say once he stayed in a hospital for check up, for those days, many vacant beds, the hospital counted on his business. He said he also sent $300 to his sister in San Francisco every month to help her, and, therefore, help the economy of California. Soon, he is going to leave Edison NJ and fly to San Diego CA to visit his 2nd son, he said he wanted to help economy in CA. So, you know if Dr Jyh can live up to 120 years old, he is going to be able to help the economy a lot by continue spending money. My neighbor Sail is also close to 80 year old, and he just bought a brand new car, i.e. created a full time job. He also got his driveway redone, dozen workers came working a whole week, now so new so shine. Then, he decided he got more money than can live long enough, so he got workers to wash his houses every year, and have landscapers to mow the lawn and plant trees, ...etc. Then he took his grandchildren to Chuck E Cheese, to many museums ...etc. Again, helping the economy a lot! If they have died in 68, then, the economy may have been even worse. How about Warren Buffett? or Bill Gates? If they can live up to 120 years old or even 150 years old, then the economy may be much better than if they die earlier, right? Look at Steve Jobs, he may died well before 68 year old, and Apple stocks may collapse, and billions wealth may disappear...

Avatar of:

Posts: 0

September 14, 2011

"Unaccepatable question"? Not sure there are any...AND I am betting you are not 67!  I for one wish to live as long, healthy and productive life as possible.  Can't understand why anyone wouldn't want to; but then we as individuals have the option to end it any time.  I am much, much more disturbed by folks who want to inflict their personal opinions/values on the rest of us...
 I will second Kevin Perrott's post!

Avatar of:

Posts: 0

September 14, 2011

This is very interesting and valuable. It seems human can keep the memory forever. I have built a human brain over Internet, and it seems able to conduct what I want it to. e.g. I can make any home sold in a day or two. It sounds like magic, but it is not because human brain all interconnected. In any case, my Internet brain also suffer "mercury" type of damaging, so the memory kept loosing, here and there. Your posting reminds me to check out what it the equivalent "mercury" in my Internet Brain.

Avatar of:

Posts: 0

September 14, 2011

Do we have the right to live that long ? Good wits and diapers included?
Capable to atribute to mankind-- bullsh..! Procreation capability has degenerated so the inborn feroucious wish to go on...like greatgrandma prepairing breakfast for greatgrandchildren ...till what age she should be permitted....? Wrinckels look prozaic..but when you have turned a pain in the ass ....your brain is not good enough to consider that question... do you have the right to live that long?
How old grew Mr Altzheimer? Anybody rembers..?

Avatar of:

Posts: 0

September 14, 2011

This is really very funny ,I like it very much ,Thank you for the post !I would also like to share you with some good ideas about HP Pavilion G60 battery.

Avatar of:

Posts: 0

September 14, 2011

She must not have browsed Internet too much. If one browses Internet so much and so powerful (e.g. like myself with hundreds of windows and tabs open, pop up, swap, ...etc. your brain will got too much and all interconnected to each other, yet you can NOT use your mouth to describe. It is like a binary code with no source code).

Avatar of:

Posts: 0

September 14, 2011

You may want to add "psychology", "nuroscience" to your field, basically, Pshchology is the learning of "human software" and Nuroscience is "human hardware", in particular the brain hardware.

Avatar of:

Posts: 0

September 14, 2011

True or False, depending on how much knowledge you got to understand this wonderful article. First, you got to know Finite Automata and Formal Language well enough to appreciate this finding. Second, this article gives me a thought of building "Extra Hippocampus", in other words, one does NOT always count on its own brain and memory. Like people after seizure often forgot many things, but with help of iPhone to continually taking photos every now and then, those photos can help recover memory after seizure. So, you are talking about if it is the "hardware" damage of the aging brain or the "software problem". In the article, apparently, the alzheimer is "hardware damage", i.e. CA1 and the other cortex, like if your computer hard disk damage, you can not retrieve info. However, the article also prove that it is NOT "hardware" damage for many aging, the CA1 and CA3 not change, but the Dentate Syrup and the responsive. It is like, when you open too many windows or tabs in your browsers, you got slower response, but all the hardware have NO problem. So, to increase the speed or response, just simply kill some windows or close some tabs, and the speed regain. In that regard, isn't that aging brain easy to fix? A young mind is like a new computer or a newly hire to start a browser, few windows open and few tabs open too, so the response is fast, yet the more experience employees may end up have lots of windows and tabs open, and became slow. You can deem this is also "aging". But, neither has "hardware" problem. So, when you talk about "disease", you need to distinguish whether it is "hardware" or "software" problem. Aging could result either or both, and if it is NOT hardware problem, it often can be easily fix, if you know the bug. If it is hardware problem, you want to see if you can find the parts for replacement, otherwise, it is gone forever.

Avatar of:

Posts: 0

September 14, 2011

Before you start losing your memory, I suggest that you take many photos with your iPhone or the like, and write many blogs to document many things that will someday always "supplement" your memory. Human memory is like "capacitor charging", you charge once and it may die away along time, but if you charge it back frequent enough, it will be fresh. On the other hand, when you have so many memory to charge (i.e. aging brain), you will NOT have enough time cycle to do so. So, an auxiliary memory always help a lot!

Avatar of:

Posts: 0

September 14, 2011

She must not have browsed Internet too much. If one browses Internet so much and so powerful (e.g. like myself with hundreds of windows and tabs open, pop up, swap, ...etc. your brain will got too much and all interconnected to each other, yet you can NOT use your mouth to describe. It is like a binary code with no source code).

Avatar of:

Posts: 0

September 14, 2011

You may want to add "psychology", "nuroscience" to your field, basically, Pshchology is the learning of "human software" and Nuroscience is "human hardware", in particular the brain hardware.

Avatar of:

Posts: 0

September 14, 2011

True or False, depending on how much knowledge you got to understand this wonderful article. First, you got to know Finite Automata and Formal Language well enough to appreciate this finding. Second, this article gives me a thought of building "Extra Hippocampus", in other words, one does NOT always count on its own brain and memory. Like people after seizure often forgot many things, but with help of iPhone to continually taking photos every now and then, those photos can help recover memory after seizure. So, you are talking about if it is the "hardware" damage of the aging brain or the "software problem". In the article, apparently, the alzheimer is "hardware damage", i.e. CA1 and the other cortex, like if your computer hard disk damage, you can not retrieve info. However, the article also prove that it is NOT "hardware" damage for many aging, the CA1 and CA3 not change, but the Dentate Syrup and the responsive. It is like, when you open too many windows or tabs in your browsers, you got slower response, but all the hardware have NO problem. So, to increase the speed or response, just simply kill some windows or close some tabs, and the speed regain. In that regard, isn't that aging brain easy to fix? A young mind is like a new computer or a newly hire to start a browser, few windows open and few tabs open too, so the response is fast, yet the more experience employees may end up have lots of windows and tabs open, and became slow. You can deem this is also "aging". But, neither has "hardware" problem. So, when you talk about "disease", you need to distinguish whether it is "hardware" or "software" problem. Aging could result either or both, and if it is NOT hardware problem, it often can be easily fix, if you know the bug. If it is hardware problem, you want to see if you can find the parts for replacement, otherwise, it is gone forever.

Avatar of:

Posts: 0

September 14, 2011

Before you start losing your memory, I suggest that you take many photos with your iPhone or the like, and write many blogs to document many things that will someday always "supplement" your memory. Human memory is like "capacitor charging", you charge once and it may die away along time, but if you charge it back frequent enough, it will be fresh. On the other hand, when you have so many memory to charge (i.e. aging brain), you will NOT have enough time cycle to do so. So, an auxiliary memory always help a lot!

Avatar of:

Posts: 0

September 14, 2011

Aging provides the fruits of age in the products of knowledge, experience and wisdom. To ask why we should spend out resources and efforts in order to prolong prolonging life is answered in the gift that we pass on with all the above to our own and civilization's creative treasure.  

Avatar of:

Posts: 0

September 14, 2011

You should talk to Dr. Jyh who got Ph.D from Columbia Univ and just passed 80 year old. Why? He always believe he can live up to 120 years old, so I introduced Prof Kan to him, who believe he can live up to 150 years old, and the trick is to live LONG enough to catch the medical advance to extend human life. Every Sping Dr. Jyh will come back from Key West FL to Edison NJ, and in Fall, he went back to Key West FL because he believe the cold temperature will shorter his life, same as hot temperature. So, he end up live like birds. In current economy situation, everyone like Dr. Jyh because wherever he goes, he spend. e.g. He would rent a place at Key West FL for $700 a month, month to month, where most units were vacant, and he would rent a furnished room in Edison NJ when Rutgers University students went back home in summer. He would buy a new computer and sold his Toyota Corolla 96 to someone desperately needed in Key West FL. He would go visit many doctors and do check up in whichever hospital with new technology to make sure he is healthy all the time, and therefore, they all make money. Dr. Jyh was very proud to say once he stayed in a hospital for check up, for those days, many vacant beds, the hospital counted on his business. He said he also sent $300 to his sister in San Francisco every month to help her, and, therefore, help the economy of California. Soon, he is going to leave Edison NJ and fly to San Diego CA to visit his 2nd son, he said he wanted to help economy in CA. So, you know if Dr Jyh can live up to 120 years old, he is going to be able to help the economy a lot by continue spending money. My neighbor Sail is also close to 80 year old, and he just bought a brand new car, i.e. created a full time job. He also got his driveway redone, dozen workers came working a whole week, now so new so shine. Then, he decided he got more money than can live long enough, so he got workers to wash his houses every year, and have landscapers to mow the lawn and plant trees, ...etc. Then he took his grandchildren to Chuck E Cheese, to many museums ...etc. Again, helping the economy a lot! If they have died in 68, then, the economy may have been even worse. How about Warren Buffett? or Bill Gates? If they can live up to 120 years old or even 150 years old, then the economy may be much better than if they die earlier, right? Look at Steve Jobs, he may died well before 68 year old, and Apple stocks may collapse, and billions wealth may disappear...

Avatar of:

Posts: 0

September 14, 2011

"Unaccepatable question"? Not sure there are any...AND I am betting you are not 67!  I for one wish to live as long, healthy and productive life as possible.  Can't understand why anyone wouldn't want to; but then we as individuals have the option to end it any time.  I am much, much more disturbed by folks who want to inflict their personal opinions/values on the rest of us...
 I will second Kevin Perrott's post!

Avatar of:

Posts: 0

September 19, 2011

Sirs,

 in a
previous paper (www.semeioticabiofisica.it)
I described an original biophysical semeiotic method, easy to apply at the
bed-side and reliable in recognizing Alzheimer’s Disease, even in early and/or
symptomless stage. I agree with R Kale (1) who wrote that “tackling the
problems posed by the neurodegenerative disorders is difficult. We could draw
inspiration from the former US
president (R. Reagan) who survived falls from horses, cancer of the skin and
colon, and a bullet in the chest and is now quietly battling Alzheimer'sâ€쳌.
However, as usually, also in such neurodegenerative disorders, in my opinion,
we must aim to the early “clinicalâ€쳌 diagnosis, possibly soon after disease
on-set, or better in the so-called “pre-pathologicalâ€쳌 phase, i.e. “real riskâ€쳌
of disease. Morover, the diagnosis must be necessarily “clinicalâ€쳌, because GPs,
who at first visit these patients, have to recognize the very initial or
“pre-pathologicalâ€쳌 stages, characterized by modification of Neuronal and
Cerebral Evoked Potentials, nowadays assessed bed-side by means of Biophysical
Semeiotics (See: Cerebral Tumour, in above-cited web site). As I have written
in former papers (2, 3) and in my web site, “Early clinical
biophysical-semeiotic Diagnosis of Alzheimer’s Diseaseâ€쳌, I gathered interesting
data, due to the fact that there is notoriously an association between high
serum cholesterol, raised blood pressure and, finally, insulin-resistance.
Briefly, in healthy, from the microcirculatory view-point, during stress test,
both vasomotility (chaotic-deterministic oscillations of arterioles) and
vasomotility (secondary chaotic-deterministic fluctuations of nutritional
capillaries and post-capillary venules) particularly in hippocampus, pre-
frontal and parietal cerebral regions are maximally activated. (2, 3, 4, 5). On
the contrary, in individuals with a family history positive for Alzheimer’s
disease and, of course, in patients in the early stage, under identical
conditions appears a particular form of microcirculatory activation,
characterized by increased vasomotility and decreased vasomotion (I termed it
dissociated type). In a few words, techniically speaking, the flow- and
flux-motion in the cerebral microcirculatory bed appears to be clearly
decreased, due to the dangerous phenomenon of the so-called “microcirculatory
blood-flow centralizationâ€쳌. Unfortunately, it is generally admitted that
diagnosing Alzheimer’s disease, particularly in initial stages, is very
difficult. In my 47-year-long clinical experience the test of acute pick of
insulin secretion (2, 3) proved to be reliable in bed-side recognizing this
(and other numerous) disorder, even in its first stage. Although insulin isn’t
necessary in the glucose utilizations of cerebral neurons, surely in both
cerebral cortex and hippocampus there is a largely amounts of insulin receptors
(6). In initial stages of the disease has been demonstrated a scarse glucose
metabolism in cerebral tissue: venous glucose level appears to be slightly
decreased (6). The authors, in addition, demonstrated that O2 consumption is
unchanged, due to the fact that the neurons utilize other “endocellularâ€쳌
substances rather than glucose, probably causing neurons death (7). Although
insulin isn’t necessary in glucose utilizations of cerebral neurons, however in
both cerebral cortex and hippocampus there is surely a largely amounts of
insulin receptors (6). In addition, in the initial stages of the disease has
been demonstrated a scarse glucose metabolism in cerebral tissue: venous
glucose level appears to be slightly decreased (6). These authors, moreover,
demonstrated that O2 consumption is unchanged, due to the fact that the neurons
utilize other “endocellularâ€쳌 substances rather than glucose.

1) Kale R.
Neurodegenerative disorders. BMJ 2001;323:879-880 ( 20 October ).

2) Stagnaro S., Valutazione percusso- ascoltatoria della
microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It.
di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta
Med.Medit. 145, 163 1986.

3) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di
Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-
insulinoresistenza. Acta Med. Medit. 13, 125 1997.

4 Stagnaro S., Stagnaro-Neri M., Valutazione percusso - ascoltatoria
degli attacchi ischemici transitori e della insufficienza cerebrovascolare
cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It.
Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G.
Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna 1987.

5) Stagnaro S., Stagnaro-Neri M., Il Test dell’Apnea nella Valutazione
della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita.
Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457,
Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna 1987

6) Hoyer S. Models of
Alzheimer’s disease: cellular and molecular aspects. Journal of
Neurotrasmission.(Suppl.) 49, 11, 1997.

7) Baringai M. Is
Apoptosis Key in Alzheimer’s Disease? Science. 281, 1301, 28 August 1998

8) Koudinov A.R.,
Koudinova N.R.Brain cholesterol pathology is the cause of alzheimer’s disease.
Clin. Med. & Health Research, November, 2001.   

 
 

Avatar of: Sergio Stagnaro

Anonymous

September 19, 2011

Sirs,

 in a
previous paper (www.semeioticabiofisica.it)
I described an original biophysical semeiotic method, easy to apply at the
bed-side and reliable in recognizing Alzheimer’s Disease, even in early and/or
symptomless stage. I agree with R Kale (1) who wrote that “tackling the
problems posed by the neurodegenerative disorders is difficult. We could draw
inspiration from the former US
president (R. Reagan) who survived falls from horses, cancer of the skin and
colon, and a bullet in the chest and is now quietly battling Alzheimer'sâ€쳌.
However, as usually, also in such neurodegenerative disorders, in my opinion,
we must aim to the early “clinicalâ€쳌 diagnosis, possibly soon after disease
on-set, or better in the so-called “pre-pathologicalâ€쳌 phase, i.e. “real riskâ€쳌
of disease. Morover, the diagnosis must be necessarily “clinicalâ€쳌, because GPs,
who at first visit these patients, have to recognize the very initial or
“pre-pathologicalâ€쳌 stages, characterized by modification of Neuronal and
Cerebral Evoked Potentials, nowadays assessed bed-side by means of Biophysical
Semeiotics (See: Cerebral Tumour, in above-cited web site). As I have written
in former papers (2, 3) and in my web site, “Early clinical
biophysical-semeiotic Diagnosis of Alzheimer’s Diseaseâ€쳌, I gathered interesting
data, due to the fact that there is notoriously an association between high
serum cholesterol, raised blood pressure and, finally, insulin-resistance.
Briefly, in healthy, from the microcirculatory view-point, during stress test,
both vasomotility (chaotic-deterministic oscillations of arterioles) and
vasomotility (secondary chaotic-deterministic fluctuations of nutritional
capillaries and post-capillary venules) particularly in hippocampus, pre-
frontal and parietal cerebral regions are maximally activated. (2, 3, 4, 5). On
the contrary, in individuals with a family history positive for Alzheimer’s
disease and, of course, in patients in the early stage, under identical
conditions appears a particular form of microcirculatory activation,
characterized by increased vasomotility and decreased vasomotion (I termed it
dissociated type). In a few words, techniically speaking, the flow- and
flux-motion in the cerebral microcirculatory bed appears to be clearly
decreased, due to the dangerous phenomenon of the so-called “microcirculatory
blood-flow centralizationâ€쳌. Unfortunately, it is generally admitted that
diagnosing Alzheimer’s disease, particularly in initial stages, is very
difficult. In my 47-year-long clinical experience the test of acute pick of
insulin secretion (2, 3) proved to be reliable in bed-side recognizing this
(and other numerous) disorder, even in its first stage. Although insulin isn’t
necessary in the glucose utilizations of cerebral neurons, surely in both
cerebral cortex and hippocampus there is a largely amounts of insulin receptors
(6). In initial stages of the disease has been demonstrated a scarse glucose
metabolism in cerebral tissue: venous glucose level appears to be slightly
decreased (6). The authors, in addition, demonstrated that O2 consumption is
unchanged, due to the fact that the neurons utilize other “endocellularâ€쳌
substances rather than glucose, probably causing neurons death (7). Although
insulin isn’t necessary in glucose utilizations of cerebral neurons, however in
both cerebral cortex and hippocampus there is surely a largely amounts of
insulin receptors (6). In addition, in the initial stages of the disease has
been demonstrated a scarse glucose metabolism in cerebral tissue: venous
glucose level appears to be slightly decreased (6). These authors, moreover,
demonstrated that O2 consumption is unchanged, due to the fact that the neurons
utilize other “endocellularâ€쳌 substances rather than glucose.

1) Kale R.
Neurodegenerative disorders. BMJ 2001;323:879-880 ( 20 October ).

2) Stagnaro S., Valutazione percusso- ascoltatoria della
microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It.
di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta
Med.Medit. 145, 163 1986.

3) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di
Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-
insulinoresistenza. Acta Med. Medit. 13, 125 1997.

4 Stagnaro S., Stagnaro-Neri M., Valutazione percusso - ascoltatoria
degli attacchi ischemici transitori e della insufficienza cerebrovascolare
cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It.
Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G.
Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna 1987.

5) Stagnaro S., Stagnaro-Neri M., Il Test dell’Apnea nella Valutazione
della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita.
Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457,
Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna 1987

6) Hoyer S. Models of
Alzheimer’s disease: cellular and molecular aspects. Journal of
Neurotrasmission.(Suppl.) 49, 11, 1997.

7) Baringai M. Is
Apoptosis Key in Alzheimer’s Disease? Science. 281, 1301, 28 August 1998

8) Koudinov A.R.,
Koudinova N.R.Brain cholesterol pathology is the cause of alzheimer’s disease.
Clin. Med. & Health Research, November, 2001.   

 
 

Avatar of:

Posts: 0

September 19, 2011

Sirs,

 in a
previous paper (www.semeioticabiofisica.it)
I described an original biophysical semeiotic method, easy to apply at the
bed-side and reliable in recognizing Alzheimer’s Disease, even in early and/or
symptomless stage. I agree with R Kale (1) who wrote that “tackling the
problems posed by the neurodegenerative disorders is difficult. We could draw
inspiration from the former US
president (R. Reagan) who survived falls from horses, cancer of the skin and
colon, and a bullet in the chest and is now quietly battling Alzheimer'sâ€쳌.
However, as usually, also in such neurodegenerative disorders, in my opinion,
we must aim to the early “clinicalâ€쳌 diagnosis, possibly soon after disease
on-set, or better in the so-called “pre-pathologicalâ€쳌 phase, i.e. “real riskâ€쳌
of disease. Morover, the diagnosis must be necessarily “clinicalâ€쳌, because GPs,
who at first visit these patients, have to recognize the very initial or
“pre-pathologicalâ€쳌 stages, characterized by modification of Neuronal and
Cerebral Evoked Potentials, nowadays assessed bed-side by means of Biophysical
Semeiotics (See: Cerebral Tumour, in above-cited web site). As I have written
in former papers (2, 3) and in my web site, “Early clinical
biophysical-semeiotic Diagnosis of Alzheimer’s Diseaseâ€쳌, I gathered interesting
data, due to the fact that there is notoriously an association between high
serum cholesterol, raised blood pressure and, finally, insulin-resistance.
Briefly, in healthy, from the microcirculatory view-point, during stress test,
both vasomotility (chaotic-deterministic oscillations of arterioles) and
vasomotility (secondary chaotic-deterministic fluctuations of nutritional
capillaries and post-capillary venules) particularly in hippocampus, pre-
frontal and parietal cerebral regions are maximally activated. (2, 3, 4, 5). On
the contrary, in individuals with a family history positive for Alzheimer’s
disease and, of course, in patients in the early stage, under identical
conditions appears a particular form of microcirculatory activation,
characterized by increased vasomotility and decreased vasomotion (I termed it
dissociated type). In a few words, techniically speaking, the flow- and
flux-motion in the cerebral microcirculatory bed appears to be clearly
decreased, due to the dangerous phenomenon of the so-called “microcirculatory
blood-flow centralizationâ€쳌. Unfortunately, it is generally admitted that
diagnosing Alzheimer’s disease, particularly in initial stages, is very
difficult. In my 47-year-long clinical experience the test of acute pick of
insulin secretion (2, 3) proved to be reliable in bed-side recognizing this
(and other numerous) disorder, even in its first stage. Although insulin isn’t
necessary in the glucose utilizations of cerebral neurons, surely in both
cerebral cortex and hippocampus there is a largely amounts of insulin receptors
(6). In initial stages of the disease has been demonstrated a scarse glucose
metabolism in cerebral tissue: venous glucose level appears to be slightly
decreased (6). The authors, in addition, demonstrated that O2 consumption is
unchanged, due to the fact that the neurons utilize other “endocellularâ€쳌
substances rather than glucose, probably causing neurons death (7). Although
insulin isn’t necessary in glucose utilizations of cerebral neurons, however in
both cerebral cortex and hippocampus there is surely a largely amounts of
insulin receptors (6). In addition, in the initial stages of the disease has
been demonstrated a scarse glucose metabolism in cerebral tissue: venous
glucose level appears to be slightly decreased (6). These authors, moreover,
demonstrated that O2 consumption is unchanged, due to the fact that the neurons
utilize other “endocellularâ€쳌 substances rather than glucose.

1) Kale R.
Neurodegenerative disorders. BMJ 2001;323:879-880 ( 20 October ).

2) Stagnaro S., Valutazione percusso- ascoltatoria della
microcircolazione cerebrale globale e regionale. Atti, XII Congr. Naz. Soc. It.
di Microangiologia e Microcircolazione. 13-15 Ottobre, Salerno, e Acta
Med.Medit. 145, 163 1986.

3) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di
Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-
insulinoresistenza. Acta Med. Medit. 13, 125 1997.

4 Stagnaro S., Stagnaro-Neri M., Valutazione percusso - ascoltatoria
degli attacchi ischemici transitori e della insufficienza cerebrovascolare
cronica in pazienti trattati con mesoglicano. Atti, IX Congr. Naz. It.
Patologia Vascolare. Copanello, 6-9 Gennaio 1987. A cura di R. Del Guercio, G.
Leonardo e G. Zanini. Pg. 765, Monduzzi Ed. Bologna 1987.

5) Stagnaro S., Stagnaro-Neri M., Il Test dell’Apnea nella Valutazione
della Microcircolazione cerebrale in Cefalalgici. Atti, Congr. Naz. Soc. Ita.
Microangiologia e Microcircolazione. A cura di C. Allegra. Pg. 457,
Roma 10-13 Settembre 1987. Monduzzi Ed. Bologna 1987

6) Hoyer S. Models of
Alzheimer’s disease: cellular and molecular aspects. Journal of
Neurotrasmission.(Suppl.) 49, 11, 1997.

7) Baringai M. Is
Apoptosis Key in Alzheimer’s Disease? Science. 281, 1301, 28 August 1998

8) Koudinov A.R.,
Koudinova N.R.Brain cholesterol pathology is the cause of alzheimer’s disease.
Clin. Med. & Health Research, November, 2001.   

 
 

Avatar of:

Posts: 0

September 20, 2011

You must read this or you will miss a lot in understanding aging.
Shi V. Liu’s Views on Aging and the Ignorance by Mainstream
(http://im1.biz/Aging.htm)

Avatar of:

Posts: 0

September 20, 2011

Excuse my skepticism, but surely there is still no plausible explanation at all for the mechanism of long-term memory.  LTP is a very short term phenomenon.

I find it very difficult to separate the hype from reality in memory research.

Avatar of: Shi V. Liu

Anonymous

September 20, 2011

You must read this or you will miss a lot in understanding aging.
Shi V. Liu’s Views on Aging and the Ignorance by Mainstream
(http://im1.biz/Aging.htm)

Avatar of: David Colquhoun

Anonymous

September 20, 2011

Excuse my skepticism, but surely there is still no plausible explanation at all for the mechanism of long-term memory.  LTP is a very short term phenomenon.

I find it very difficult to separate the hype from reality in memory research.

Avatar of:

Posts: 0

September 20, 2011

You must read this or you will miss a lot in understanding aging.
Shi V. Liu’s Views on Aging and the Ignorance by Mainstream
(http://im1.biz/Aging.htm)

Avatar of:

Posts: 0

September 20, 2011

Excuse my skepticism, but surely there is still no plausible explanation at all for the mechanism of long-term memory.  LTP is a very short term phenomenon.

I find it very difficult to separate the hype from reality in memory research.

Avatar of:

Posts: 0

September 21, 2011

I wish to see more studies on aging brains based on the cholesterol concentration and also on uric protection on the neural nerves endings or was it really a genetic issue against Alzheimer that is really the protection.  Last decade, USA is under a massive attack on the air from chemtrails filled with aluminium. Shouldn't this be an important issue in aging analysis, can scientist considers the number of dead Alzheimer patients with their correlation with the level of blood cholesterol ,aluminium and other heavy metals poison. Believe its about time, with sufficient data we should be able to see a trend on why people above 70 were losing their memory and heading for dementia state.  for me, I will maintain a higher cholesterol as I age, I think some scientists were not telling much... Heart vs brain in cholesterol, I wants to think,learn and reason well and not just to remember my past,telephone numbers and my previous holiday destinations.

Avatar of: pooable

pooable

Posts: 2

September 21, 2011

I wish to see more studies on aging brains based on the cholesterol concentration and also on uric protection on the neural nerves endings or was it really a genetic issue against Alzheimer that is really the protection.  Last decade, USA is under a massive attack on the air from chemtrails filled with aluminium. Shouldn't this be an important issue in aging analysis, can scientist considers the number of dead Alzheimer patients with their correlation with the level of blood cholesterol ,aluminium and other heavy metals poison. Believe its about time, with sufficient data we should be able to see a trend on why people above 70 were losing their memory and heading for dementia state.  for me, I will maintain a higher cholesterol as I age, I think some scientists were not telling much... Heart vs brain in cholesterol, I wants to think,learn and reason well and not just to remember my past,telephone numbers and my previous holiday destinations.

Avatar of:

Posts: 0

September 21, 2011

I wish to see more studies on aging brains based on the cholesterol concentration and also on uric protection on the neural nerves endings or was it really a genetic issue against Alzheimer that is really the protection.  Last decade, USA is under a massive attack on the air from chemtrails filled with aluminium. Shouldn't this be an important issue in aging analysis, can scientist considers the number of dead Alzheimer patients with their correlation with the level of blood cholesterol ,aluminium and other heavy metals poison. Believe its about time, with sufficient data we should be able to see a trend on why people above 70 were losing their memory and heading for dementia state.  for me, I will maintain a higher cholesterol as I age, I think some scientists were not telling much... Heart vs brain in cholesterol, I wants to think,learn and reason well and not just to remember my past,telephone numbers and my previous holiday destinations.

Avatar of:

Posts: 0

October 21, 2011

If you were approaching death--and, eventually, who isn't?--, there is a high probability you might be interested in living longer too. 

Avatar of: Wesley Miller

Wesley Miller

Posts: 1

October 21, 2011

If you were approaching death--and, eventually, who isn't?--, there is a high probability you might be interested in living longer too. 

Avatar of:

Posts: 0

October 21, 2011

If you were approaching death--and, eventually, who isn't?--, there is a high probability you might be interested in living longer too. 

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