Does taking Ibuprofen cut Alzheimer's risk or does some cause of pain cut Alzheimer's risk?
ST. PAUL, Minn. – Long-term use of ibuprofen and other drugs commonly used for aches and pains was associated with a lower risk of Alzheimer’s disease, according to a study published in the May 6, 2008, issue of Neurology®, the medical journal of the American Academy of Neurology. Previous studies have shown conflicting results, but this is the longest study of its kind.
For the study, researchers identified 49,349 US veterans age 55 and older who developed Alzheimer’s disease and 196,850 veterans without dementia. The study examined over five years of data and looked at the use of several non-steroidal anti-inflammatory drugs (NSAIDs). The veterans received medical care and prescriptions through the VA Health Care system.
The study found people who specifically used ibuprofen for more than five years were more than 40 percent less likely to develop Alzheimer’s disease. Results also showed that the longer ibuprofen was used, the lower the risk for dementia. In addition, people who used certain types of NSAIDs for more than five years were 25 percent less likely to develop Alzheimer’s disease than non-users.
While other NSAIDs such as indomethacin may also have been associated with lower risks, others such as celecoxib did not show any impact on dementia risk.
My guess is that the NSAIDs do this risk cutting. The fact that some have stronger risk reduction effects suggests the drugs themselves make the difference. Also, lots of research finds chronic inflammation increases risk of a variety of diseases of old age.
But long term NSAIDs might not reduce all cause mortality. They might increase risks of other diseases. Safer bets for Alzheimer's disease risk reduction include fruit and vegetable juices, tea, the Mediterranean Diet, fish oils, and curcumin.
Injected near the spine Enbrel delivers very rapid results.
A drug commonly used to treat arthritis caused a dramatic and rapid improvement in patients with Alzheimer's disease, according to physicians in California. However, scientists and others not involved in the work worry that the report, which was based on trials in a few patients and hasn't been independently confirmed, may offer little more than false hope for Alzheimer's sufferers and their families.
Alzheimer's patients injected with the anti-inflammatory drug etanercept--marketed as Enbrel--showed dramatic improvements in their functioning within minutes, according to Edward Tobinick, director of the Institute for Neurological Research, a private medical facility in Los Angeles where the patients were treated, and an assistant clinical professor of medicine at the University of California, Los Angeles.
"The patients improve literally before your eyes," says Tobinick, who began using etanercept in Alzheimer's patients three years ago. He uses an unconventional method to administer the drug; he injects it near patients' spines.
Will affluent Alzheimer's sufferers seek out doctors capable of delivering this treatment? Will it spread even without big clinical trials to check its effectiveness? Think about it. If you had early stage Alzheimer's would you try something like this? I would.
Suppose this turns out to work really well. If the relief from this treatment is long lasting then the methods under development to detect beta amyloid plaque years before disease diagnosis will end up getting used in routine screenings of people in their 40s and 50s. One way or another early detection will get used to trigger the use of preventive treatments against Alzheimer's once such treatments become available.
Will trying to make yourself more conscientious slow your brain's aging? Or is conscientiousness a genetically caused trait? What is the mechanism fort this effect?
Individuals who are more conscientious—in other words, those with a tendency to be self-disciplined, scrupulous and purposeful—appear less likely to develop Alzheimer’s disease, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Conscientiousness refers to a person’s tendency to control impulses and be goal-directed, and is also known as will, work and dependability, according to background information in the article. It has been associated with a wide range of mental and physical disorders, disability and death, suggesting it may be important for maintaining overall health.
Robert S. Wilson, Ph.D., of Rush University Medical Center, Chicago, and colleagues studied 997 older Catholic nuns, priests and brothers who did not have dementia when the study began in 1994. Participants underwent evaluations that included medical history, neurologic examinations and cognitive testing. Conscientiousness was measured with a 12-item inventory, where participants rated agreement with each item (for example, “I am a productive person who always gets the job done”) on a scale of one to five. Scores ranged from zero to 48, with higher scores indicating more conscientiousness. The researchers conducted follow-up examinations annually through 2006, with an average of 7.9 evaluations per person.
The participants had an average conscientiousness score of 34 out of 48. Through a maximum of 12 years of follow-up, 176 individuals developed Alzheimer’s disease. Those who had conscientiousness scores in the 90th percentile (40 points) or higher had an 89 percent lower risk of developing Alzheimer’s disease than those whose scores ranked in the 10th percentile (28 points) or lower. Controlling for known Alzheimer’s disease risk factors did not substantially change these results. Conscientiousness also was associated with a slower rate of cognitive decline and a lower risk of mild cognitive impairment, a condition that may precede Alzheimer’s disease.
Maybe conscientious people take better care of themselves and eat better food. The Mediterranean diet appears to lower Alzheimer's risk for example. So do conscientious driven people adopt the best dietary advice at a higher rate than do less conscientious and less goal-oriented people? Seems highly plausible.
Or maybe being driven they stimulate their minds harder their entire lives. build up more neurons, and therefore have more cognitive reserves to lose before the symptoms of Alzheimer's becomes apparent.
Or maybe the genetic variants that make people driven also somehow protect the body against brain aging?
What is the most important thing to know about Alzheimer's Disease? You don't want to get it and you don't want anyone you care about to get it either. You want cures for it sooner rather than later. We should try to stop and reverse brain aging.
Here is more evidence htat Alzheimer's Diseases is a type of insulin resistant diabetes.
EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a novel third form of diabetes.
Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer’s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer’s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for “amyloid ß-derived diffusible ligand.”)
With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer’s disease, the Northwestern study sheds light on the emerging idea of Alzheimer’s being a “type 3” diabetes.
Insulin serves multiple functions. The best known is that it binds on the surface of cells and causes the cells to pull sugar out of the bloodstream. But the lack of binding by insulin on neurons in Alzheimer's might wreak damage due to interference with other processes which insulin helps regulate.
Development of the ability to block the accumulation of these ADDL proteins might provide a way to stop Alzheimer's. But the research on insulin resistance in Alzheimer's suggests that treatments used for type 2 insulin resistant diabetes might help also. Or drugs could be developed to block ADDL binding to insulin receptors.
“We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,” said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. “Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer’s disease.”
ADDLs are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer’s disease and block memory function by a process predicted to be reversible.
Alzheimer's is a horrible disease. Your brain slowly dies while your body remains living. You know it is happening until you reach the point where you can't even remember that much.
Why do the ADDLs accumulate in the first place? We need treatments that will stop Alzheimer's by stopping the very earliest steps in the disease. Is toxic protein accumulation the earliest step? Or is the earliest step something that causes the toxic proteins to start accumulating?
Wisdom comes with age (doesn't it?), but not without a process that takes place in the brain called myelination. Myelin is the fatty sheath that coats the axons of the nerves, allowing for efficient conduction of nerve impulses. It is key to the fast processing speeds that underlie our higher cognitive functioning, including, yes, wisdom.
Myelination continues sheathing axons until we reach the age of about 50, but in these later stages, the myelin becomes more and more susceptible to damage. Now, in a report in the April issue of the journal Alzheimer's & Dementia, Dr. George Bartzokis, UCLA professor of neurology, suggests that it is the breakdown of this late-stage myelin that promotes the buildup of toxic amyloid-beta fibrils that eventually deposit in the brain and become the plaques which have long been associated with Alzheimer's disease.
These amyloid products in turn destroy more and more myelin, according to Bartzokis, disrupting brain signaling and leading to cell death and the classic clinical signs of Alzheimer's. If correct, the research suggests a broader approach to therapeutic interventions for the disease.
If myelin breakdown is behind Alzheimer's then that strongly suggests to me that brain rejuvenation therapies that repair and replace myelin would be most effective at preventing and stopping Alzheimer's.
Late stage added myelin is thinner and breaks down more easily.
"Myelination of the brain follows an inverted U-shaped trajectory, growing strongly until middle age. Then it begins to breakdown," Bartzokis said. "Before the advent of modern medicine, very few persons lived beyond age 50 and therefore, as a species, we evolved to continue myelinating over our entire natural life span."
As a result, the volume of myelinated white matter increases to a peak at about age 50, then slowly begins to reverse and decline in volume as we continue to age. The myelin that is deposited in adulthood ensheaths increasing numbers of axons with smaller axon diameters, and so spreads itself thinner and thinner, he said. As a result, it becomes more susceptible to the ravages of age in the form of environmental and genetic insults and slowly begins to break down.
Your myelin slowly breaks down after age 50. That, by itself, is thoroughly disgusting even before we consider the threat from Alzheimer's. The brain is our most powerful tool. Our brains become less powerful. In the process of its decay and aging we become less capable and lose parts of who we are. Shouldn't we try much harder with research funding to find ways to stop and reverse brain aging?
Dr. Bartzokis found that the areas of the brain with the latest myelin formation are the areas where amyloid plaques form.
Oligodendrocytes and myelin have the highest levels of iron of any brain cells, Bartzokis said, and circumstantial evidence supports the possibility that brain iron levels might be a risk factor for age-related neurodegenerative diseases like Alzheimer's. In the study, he suggests that myelin breakdown in the late-myelinating regions releases iron, which promotes the development of the toxic amyloid oligomers and plaques, which in turn destroy more myelin.
Bartzokis tested his hypothesis by examining published images of amyloid deposition acquired in living individuals; the images were made using radiolabeled ligands molecules that bind to amyloid plaques in the brains of Alzheimer's patients. Next, he compared the physical location of these plaques to much earlier work published in a the Lancet in 1901 that mapped the locations in the brain where late-stage myelination occurs. The two matched up perfectly.
Stem cells and gene therapy are both strong contenders to some day serve treatments to re-myelinate aging brains. We need faster rates of research into both approaches.
Treatments that stop and reverse nerve demyelination will some day boost worker productivity and increase the rate of economic growth. We should try 10 times harder to develop those treatments.
Years before an Alzheimer's diagnosis scans of the brain show changes.
ST. PAUL, Minn – People who develop dementia or Alzheimer's disease experience brain structure changes years before any signs of memory loss begin, according to a study published in the April 17, 2007, issue of Neurology®, the scientific journal of the American Academy of Neurology. Researchers say these findings may help identify people at risk of developing mild cognitive impairment (MCI), which leads to Alzheimer's disease.
Researchers performed brain scans and cognitive tests on 136 people over the age of 65 who were considered cognitively normal at the beginning of the five-year study. Participants were then followed annually with neurologic examination and extensive mental status testing. By the end of the study, 23 people had developed MCI, and nine of the 23 went on to be diagnosed with Alzheimer's disease. The brain scans of the 23 people with memory loss were then compared to the 113 people who remained cognitively normal.
Compared to the group that didn't develop memory problems, the 23 people who developed MCI or Alzheimer's disease had less gray matter in key memory processing areas of their brains even at the beginning of the study when they were cognitively normal.
Your brain is aging. It is getting older every day. Alzheimer's Disease isn't something you just catch one day and start forgetting things the next day and get diagnosed a week later. Your brain accumulates damage over a period of years until finally the brain can't compensate for the losses.
Some people think aging is okay because it is graceful and you get old and wise and gray. But aging isn't nice. Aging is destruction, not wisdom. Brain aging will turn into Alzheimer's if you live long enough. A recent Plos One article states: Virtually the entire population has Alzheimer-related pathology (amyloid plaques and neurofibrillary tangles) by age 90 years .
We need brain rejuvenation therapies. Vascular stem cells will help repair decaying arteries, capillaries, and veins to improve brain cell food supplies. Gene therapies will conduct repairs on genomes of neurons. Gene therapies, drugs and immunotherapies will help to clear away accumulated debris. We need a much larger research effort to develop all the therapies we need to make our minds young again. The costs will get paid back many times over in increased productivity and more rapid economic growth.
Researchers at the University of Pennsylvania School of Medicine have shown that impaired function and loss of synapses in the hippocampus of a mouse form of Alzheimer’s disease (AD) is related to the activation of immune cells called microglia, which cause inflammation. These events precede the formation of tangles – twisted fibers of tau protein that build up inside nerve cells – a hallmark of advanced AD. The researchers report their findings in the February 1 issue of Neuron.
The microglia might cause the tau protein to get all bent out of shape. Then the tau proteins can't get transported to stabilize microtubules. That causes the loss of the transport mechanism and the nerves collapse since needed stuff isn't getting delivered.
So why do the microglia get activated in the first place? Even before the tau protein gets bent out of shape it accumulates. But why does the tau protein accumulate? This report does not answer that question but one potential answer is that aged nerve cells cease to make enough energy to run their internal transport and internal trash destruction mechanisms.
“Abolishing the inflammation caused by the accumulation of the tau protein might be a new therapy for treating neurodegenerative disorders,” says senior author Virginia Lee, PhD, Director of the Center for Neurodegenerative Disease Research. “This work points the way to a new class of drugs for these diseases.”
In addition, the immunosuppressant FK506 diminishes neuron loss and extends the life span of the transgenic Alzheimer’s mice. Normally only 20 percent of these mice survive by one year. With FK506, 60 percent of the mice were alive by one year.
But methods to suppress the immune response, while potentially useful for therapeutic purposes, probably won't get at the original cause of Alzheimers. Decreased blood flow might be the real cause of Alzheimer's Disease.
The latest findings from the University of Rochester Medical Center mesh not only with Dr. Azheimer's initial observations but also with new findings from today's best imaging technologies. While the first visible symptom of Alzheimer's may be a person forgetting names or faces, the very first physical change is actually a decline in the amount of blood that flows in the brain. Doctors have found that not only is blood flow within the brain reduced, but that the body's capacity to allocate blood to different areas of the brain on demand is blunted in people with the disease.
"A reduction in blood flow precedes the decline in cognitive function in Alzheimer's patients," said Berislav Zlokovic, M.D., Ph.D., professor in the Department of Neurological Surgery and a neurovascular expert whose research is causing scientists to consider the role of reduced blood flow in Alzheimer's disease.
"People used to say, well, the brain is atrophying because of the disease, so not as much blood as usual is needed. But perhaps it's the opposite, that the brain is dying because of the reduced blood flow," he added.
Perhaps this phenomenon is at work on a lesser scale with many people whose minds decay to a lesser extreme without getting diagnosed with Alzheimer's. If so then a treatment to prevent this would likely reduce the rate of cognitive decline even in people who never are going to get Alzheimer's.
Look at how they were able to make this discovery. It is only because gene array chips allow the measurement of the activity of thousands of genes that these scientists were able to get clues that the problem was in the vascular system.
The first step in the study came when Zlokovic's team compared the activity of genes in the brain from several people with Alzheimer's who had died, to that of several people without the disease who had died. It's a type of study widely done now by scientists looking at a host of diseases, using vast gene arrays that can tell how active thousands of genes are in a part of the body.
Scientists have been chasing after the cause of Alzheimer's Disease for decades. But now they have the technological tools to figure out the puzzle and they are coming up with answers that eluded them until now. Think about what that portends for the future of biomedical research into the causes of diseases. The gene chips, microfluidic chips (think "lab on a chip"), and other tools are going to keep getting better at a rapid rate.
The scientists were able to narrow their search down to two key genes that regulate contraction of muscle cells found in arteries.
As Zlokovic perused the list of genes whose activity differed depending on whether the person had Alzheimer's or not, he recognized that several play a role in constricting the arteries. He asked colleague Joseph Miano, Ph.D., a cardiovascular researcher and expert on the smooth muscle that makes up part of the arteries, to take a look.
Miano recognized the group as genes that are all controlled by one of two master regulators of gene activity in smooth muscle cells. Those proteins, myocardin and SRF (serum response factor), are well known for the control they exert on blood vessel walls. Working together, the two are the chief players that regulate how much the smooth muscle cells inside the arteries contract. The more the cells contract, the narrower the artery becomes, and the less blood that flows.
They discovered that SRF and myocardin are more active in Alzheimer's brains, that greater activity of SRF and myocardin causes blood vessels to contract, and that silencing SRF allowed blood to flow more freely. So we might be able to prevent Alzheimer's with a drug that turns down SRF or myocardin.
Now we need a way to detect at an early stage that SRF and myocardin are overactive. You do not want to lose a big chunk of your brain before getting diagnosed with Alzheimer's. We also need to know why these genes become overactive in the brains of some old people. With that knowledge scientists could develop ways to prevent the whole chain of events from ever getting started.
Thanks to Lou Pagnucco for the tip on the second article.
Want to know if you'll slowly lose all your memory and control of your body in your 70s and 80s? Probably not. Hopefully a cure for Alzheimer's won't take more than 10 or 15 years and any genetic risk you have for Alzheimer's will never get a chance to slowly destroy your mind. . But if you want to know if you are at risk a research team has identified yet another genetic variation that increases the risk of late-onset Alzheimer's Disease.
Researchers led by Howard Hughes Medical Institute (HHMI) international research scholar Peter St George-Hyslop have identified a new genetic risk factor associated with the most common form of Alzheimer's disease. The research implicates a gene called SORL1 in late-onset Alzheimer's, which usually strikes after age 65.
In an advance online publication in Nature Genetics on January 14, 2007, St George-Hyslop and colleagues connected the gene to the disease in six different groups of people, although they did not pinpoint the exact genetic mutations in SORL1 responsible for Alzheimer's. In their studies, the researchers used databases that include genetic information about people with and without Alzheimer’s disease. More than 6,800 individuals—45.8 percent of them affected with the disease—were included in the analysis, which is considered a large data set in the field, said St George-Hyslop..
These SORL1 variations join apolipoprotein E variation ApoE4 as known genetic risks for late onset Alzheimer's.
“We looked for variations of SORL1 in nine different groups of people and found those variations to be associated with an increased risk of Alzheimer's in six of them,” St George-Hyslop said. “That implies that SORL1 is not the only cause of Alzheimer's, but it's one of several. Some people with the disease will have a SORL1-related cause, and some won't.” St George-Hyslop is a professor in the department of medicine and director of the Center for Research in Neurodegenerative Disease at the University of Toronto and an HHMI international research scholar. Through its international research scholars program, HHMI supports leading scientists in 28 countries outside the United States.
The researchers studied several groups of Caucasians, one group of African Americans, one group of Hispanics from the Dominican Republic, and a group of Israeli Arabs. They tracked the SORL1 genes via single nucleotide polymorphisms, or SNPs, which are single-letter changes in a gene's sequence. They found that the Caucasians with Alzheimer's displayed a certain SNP signature at one end of the gene, while the African Americans, Hispanics, and Israeli Arabs with the disease displayed another SNP signature. “This implies that there are at least two, and possibly more, gene variants at work here,” said St George-Hyslop. “That's not unusual—in many diseases you see multiple variations that all impact a specific gene.”
So how can the scientists know that a gene has a genetic variation that contributes to a disease without knowing which particular genetic variation is responsible? See the mention of SNPs (single nucleotide polymorphisms) above. Those are locations in the genome where groups of people have single letter differences in their DNA as compared to all other groups of people. SNPs tend to occur in groups. Suppose at a particular location you have a letter A in your genome. Suppose other people have a G in that location and those who have a G have greater risk of Alzheimer's. That G usually will occur along with a group of other SNPs in nearby locations. The A at the same location will occur with letters at the same nearby SNP locations. The puzzle is to figure out which of other other nearby SNPs is the one that contributes to a disease risk.
The cost of testing for SNPs in genes is declining because chips are coming to market that can test for the presence of hundreds of thousands of SNPs at a time. The decline in SNP testing costs is enabling a growing flood of successful searches for genetic variations that contribute to disease risks. Within 5 years time I expect the number of discovered and easily testable genetic risk factors will become large enough to make personal DNA testing worthwhile.
But which risks will be worth testing for? Those you'll be able to do something about. Suppose a genetic variation makes Alzheimer's inevitable at middle age and that diet has little influence on when you'll get it. Well, I guess you could decide to avoid taking on family responsibilities that you won't be around to fulfill. But initially the biggest potential for doing something about a risk will involve risks that can be influenced by diet or exercise. What we need: genetic sample collection on big population studies of diets and lifestyles. Existing on-going longitudinal studies of diet and lifestyle risks could have their diet and lifestyle information compared against disease outcomes for those with high genetic disease risk to see if any dietary factors delayed or reduced the risk of major diseases.
What you should do when you discover 5 or 10 years hence that you have high genetic risk of a disease: Write your elected officials and argue for more research on the disease you are on course to get. Lobby for cures for diseases that will otherwise kill you and your loved ones.
Two geneticists at Massachusetts General Hospital, Lars Bertram and Rudolph Tanzi, have tried to bring order to this confused field by combining the data from many different studies. In an article in Nature Genetics earlier this month, they presented a group of 13 genes besides apolipoprotein E that have a statistically significant association with Alzheimer’s.
Dr. Tanzi said that he had run the numbers on SORL1 and that it would qualify at present for a place in his canon. “This is another gene worth paying attention to,” he added, “but we really have to wait for more replications.”
Over on the Gene Expression blog Amnestic points to evidence that APOE4 boosts episodic memory when young at the expense of greater Alzheimer's risk when you get old. APOE4 might be a variation worth having for someone being born now. The short term advantage might not cost you anything in the long run becaus 50 years from now Alzheimer's will be easily preventable.
We are going to find that many genetic variations which increase disease risks also provide benefits. The task of choosing ideal genetic variations for offspring will not be straightforward with a simple list of good genes and another list of bad genes. The best trade-offs will depend on guesses about the future availability of technologies, guesses about the shape of future societies, and one's values.
A gene known to be a major risk factor for Alzheimer's disease puts out the welcome mat for the virus that causes cold sores, allowing the virus to be more active in the brain compared to other forms of the gene. The new findings, published online in the journal Neurobiology of Aging, add some scientific heft to the idea, long suspected by some scientists, that herpes somehow plays a role in bringing about Alzheimer's disease.
The work links a form of the ApoE gene known as ApoE-4, which after advanced age is the leading known risk factor for getting Alzheimer's disease, with the form of herpes – herpes simplex 1 or HSV – that infects more than 80 percent of Americans and causes cold sores around the mouth. The findings from a group at the University of Rochester Medical Center show that the particular form of the gene that puts people at risk also creates a fertile environment for herpes in the brain, allowing the virus to be more active than other forms of the ApoE gene permit.
We need vaccines that will prevent Herpes virus infections. We also need drugs or perhaps gene therapies that'll suppress or kill Herpes in the brain and peripheral nerves.
Scientists have known for more than 15 years that the ApoE-4 gene is a player in Alzheimer's disease, but the idea that it works in concert with the herpes virus is new.
Note how we've known about the ApoE-4 link to Alzheimer's for 15 years without being able to do anything about it. That's true with many other genetic variations which have known roles in causing diseases. We lack the gene therapy technologies to intervene. Though the knowledge that specific genes play roles in development of diseases does allow many scientists to focus their attention on how those those operate and how their role may help cause diseases.
Different lines of evidence point toward an Apo-E4 plus Herpes connection with Alzheimer's.
Ruth Itzhaki of the University of Manchester has led the way with several studies showing a correlation between herpes and Alzheimer's. She has shown that Alzheimer's patients who have the ApoE-4 form of the gene have more herpes DNA in the brain regions that are affected by Alzheimer's, compared to Alzheimer's patients who also have herpes but who have a different form of the ApoE gene. And she has shown that people with the ApoE-4 version of the gene who are infected with herpes are more likely to get Alzheimer's disease than people infected with herpes who have a different form of the ApoE gene, or than people who have the ApoE-4 gene but who don't have herpes.
Other scientists have found that a herpes infection is active more often – causing the tell-tale cold sores around the mouth – in the 25 percent of people who have a copy of the ApoE-4 gene. In other words, people who are frequently troubled by cold sores are more likely to have the gene that makes them more vulnerable to Alzheimer's disease.
Every time you get a cold sore do you suffer mild brain damage? Seems plausible at least.
ApoE-4 does not increase the odds of infection but it does increase the amount of time time the virus is active.
The team found that the virus infiltrates brain cells about the same no matter which gene is involved. But they found that the subsequent activity level of the virus generally mirrored the disease-causing potential of the gene. They found that in animals with the ApoE-4 gene, the virus is less likely to be in the quiet, latent stage of its life cycle, suggesting it has more of an opportunity to replicate. In animals with the ApoE-2 gene, the virus was less active.
Brain aging is the form of aging I most want to slow down and delay. How to rejuvenate the 100 billion neurons in the brain is the hardest task facing rejuvenation medicine. We'll be able to reverse the aging of the rest of the body before we develop the ability to make the brain youthful once again. Therefore any treatments we can come up with to slow brain aging will provide great benefits and give us more time to develop brain rejuvenation therapies.
A team at University of British Columbia in Canada including Weihong Song has found that oxygen deprivation activated the gene BACE1 which causes beta anyloid production and therefore likely more plaque formation.
Song’s team found that oxygen deprivation triggers a greater activation of the BACE1 gene. More beta-amyloid means more plaques and, in turn, more neuron death. So getting enough oxygen to the brain may help stave off Alzheimer’s in people with known risk factors, says Song.
A diet that reduces your risk of heart disease will probably reduce your risk of Alzheimer's.
BACE1 converts amyloid into beta amyloid.
The link between low oxygen and plaque formation may be a gene called BACE 1, he added. This gene encodes a protein that converts the precursor amyloid molecule to the more dangerous beta-amyloid form. In their studies with mice, Song's group found that lower oxygen levels increased the activity of the gene.
Lower oxygen might also lead to Alzheimers by reducing the amount of energy available to dispose of plaque. Lower oxygen reduces the ability of cells to break down sugar for energy. The energy gets used to run many cellular processes including junk disposal. So oxygen deprivation could also work to cause brain diseases by reducing the ability of cells to take out the trash.
Eat a diet that is good for your heart and circulatory system. You'll also reduce your risk of stroke, dementia, Alzheimer's, and other degenerative diseases as well.
Here's another reason to be skeptical of claims that obesity doesn't increase mortality risks.
A long-term study of the elderly has revealed that their average rate of weight loss doubles in the year before symptoms of Alzheimer's-type dementia first become detectable. The finding may be useful to researchers seeking ways to detect and treat Alzheimer's before it causes irreversible brain damage.
The study is the first to confirm in precise detail a link between weight loss and dementia tentatively identified a decade ago. Researchers report in the September 2006 Archives of Neurology that one year before study volunteers were diagnosed with very mild dementia, their rate of weight loss doubled from 0.6 pounds per year to 1.2 pounds per year. The analysis used data from the Memory and Aging Project at the Alzheimer's Disease Research Center (ADRC) of Washington University School of Medicine in St. Louis.
Alzheimer's researchers are working hard to find biomarkers, indicators that can be used to detect the presence of Alzheimer's before clinical symptoms become obvious. Studies at the ADRC and elsewhere have strongly suggested that if Alzheimer's treatments will ever prevent lasting cognitive damage, they may have to be given to patients before memory loss and other disruptions caused by the disorder are evident.
When you read claims that being overweight is not correlated with shorter lifespans keep in mind that a number of illnesses cause weight loss before the illnesses are diagnosed. Cancer can cause weight loss. Unexpected weight loss is sometimes the reason people with undiagnosed cancer go to a doctor and end up with a cancer diagnosis. But cancer is not the only major disease common in old age that causes weight loss. As reported above, even Alzheimer's causes weight loss before diagnosis.
Botton line: People who keep their weight down as a conscious choice are mixed in with people who have lost weight due to illness. So reports which show similar risk of death in the overweight and regular weight are misleading unless they are carefully crafted to control for illness as a cause of weight loss.
A couple of recent studies did attempt to control for illness as a cause of weight loss. They used weight of their subjects before the subjects reached old age. This allowed them to reduce the bias caused by weight loss due to undiagnosed illnesses. They found that being overweight really does shorten life expectancy. See my post Two Studies Find Being Overweight Shortens Life Expectancy for the details.
A drug that treats type 2 diabetes might work against Alzheimer's.
Providence, RI – Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease, providing evidence that the disease can be treated in its early stages, according to a study by researchers at Rhode Island Hospital and Brown Medical School.
Researchers have found that peroxisome-proliferator activated receptor (PPAR) agonists prevent several components of neurodegeneration and preserve learning and memory in rats with induced Alzheimer's disease (AD). They found that an agonist for PPAR delta, a receptor that is abundant in the brain, had the most overall benefit.
"This raises the possibility that you can treat patients with mild cognitive impairment who have possible or probable Alzheimer's disease. This is really amazing because right now, there's just no treatment that works," says lead author Suzanne M. de la Monte, MD, MPH, a neuropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School in Providence, RI.
The study appears in the September issue (Volume 10, Issue 1) of the Journal of Alzheimer's Disease (www.j-alz.com).
Alzheimer's looks to be a type of diabetes that is specific to the brain.
In previous studies, the researchers demonstrated that Alzheimer's is a brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct from other types of diabetes. They showed that insulin and IGF-I receptors are produced separately in the brain, and begin to disappear early in Alzheimer's and continue to decline as the disease progresses. As insulin signaling breaks down, it leads to increased oxidative stress, impaired metabolism and cell death – all causing neurodegeneration.
Scientists were also previously able to replicate Alzheimer's in rats with Streptozotocin (STZ), a compound that is known to destroy insulin producing cells in the pancreas and cause diabetes. When injected into the brains of rats, the compound mimicked the neurodegeneration of Alzheimer's disease – plaque deposits, neurofibrillary tangles, diminished brain size, impaired cognitive function, cell loss and overall brain deterioration.
Since PPAR gamma is already approved as a treatment for Type 2 (insulin resistant) diabetes in humans it would be pretty easy to try it out in early stage Alzheimer's patients. PPAR alpha and PPAR delta would also be useful against Alzheimer's.
Having created an animal model for Alzheimer's, researchers in this study induced Alzheimer's with STZ and then administered treatment with three classes of PPAR agonists – alpha, gamma and delta. All are found in various tissues and organs in the body, including the brain, and PPAR gamma is already FDA approved as a treatment for Type 2 diabetes, or adult-onset diabetes. The two other classes of PPAR agonists have not yet been approved for clinical use.
Following treatment, many of the abnormalities associated with Alzheimer's were reduced or nearly disappeared. The agonists affected different regions of the brain, with PPAR delta producing the most striking effect in preserving the hypothalamus and temporal lobes, areas of the brain responsible for memory, learning, and behavior. In these brain regions, PPAR alpha and PPAR gamma were effective in reducing amyloid gene expression. PPAR delta had the most benefit for reducing oxidative stress and improving learning and memory.
"That was the most spectacular," de la Monte says, "because everybody wants something for cognitive impairment, and that was the most improved with the PPAR delta agonist."
Researchers were not able to stop the deterioration of insulin and its receptors. However, by administering PPAR, they were able to bypass the defects in insulin signaling and preserve the cells that need insulin to thrive. PPAR molecules go directly to the nucleus of cells and tell DNA to turn on or off genes that are normally regulated by insulin, thus preventing them from dying and allowing them to communicate with each other. The major effects of the PPAR treatments were to increase brain size, preserve insulin and IGF-II receptor bearing neurons, and preserve learning and memory.
"The trigger for dementia is the loss of insulin and IGF producing cells. The cells that need those growth factors subsequently die. This study shows you can block the second phase, which is responsible for dementia. This is great news for patients since you treat early stages of disease," de la Monte says.
Another promising result for Alzheimer's patients is that these drugs could be given in the form of a pill, de la Monte says. In the study, the drugs were injected to control the amounts administered.
"One of the most exciting findings was that peripheral (intraperitoneal) injection of the PPAR agonists either partially or completely rescued the brains from neurodegeneration," the authors write.
Alzheimer's appears to be caused by parallel abnormalities – impaired insulin signaling and oxidative stress, which is regulated by the genes NOS and NOX. The PPAR agonists treatments target both problems. They preserve the cells regulated by insulin and IGF, and they decrease oxidative stress, resulting in fewer lesions in the brain.
"If the diagnosis is suspected or patients are in the early phases of AD, there's a good possibility they could get treatment that will help them. It's possible that in the moderate phase, treatment will also help, but more work needs to be done to show that," de la Monte says.
Treatment is not likely to work in the late stages of the disease, she says, because the cells have already died.
All the reports lately about much earlier stage tests for Alzheimer's will turn out to be very useful because periodic testing as we age might be used to determine when to start treatment for type 3 diabetes.
These results remind me of other studies on brain aging. As we age glucose concentrations drop more rapidly and rise more slowly when we do mental work. Basically, our brains can not get enough glucose for sustained concentration. Is the brain glucose shortage seen in normal aging just a milder manifestation of the Type 3 diabetes that these reseachers claim is the cause of Alzheimer's? As we age would we be better able to maintain sustained concentration by taking drugs developed to stimulate insulin receptors in the brain?
Also, is Alzheimer's caused by a glucose shortage that robs the neurons of enough energy to remove the junk (e.g. beta amyloid plaque) that accumulates? Or does the lack of stimulation of the insulin receptors reduce the signalling that tells intracellular machinery to break down the accumulated junk?
Thanks to Lou Pagnucco for the heads up.
Want to lower your Alzheimer's risk by 76%?
In a large epidemiological study, researchers found that people who drank three or more servings of fruit and vegetable juices per week had a 76 percent lower risk of developing Alzheimer’s disease than those who drank juice less than once per week.
The study by Qi Dai, M.D., Ph.D., assistant professor of Medicine, and colleagues appears in the September issue of The American Journal of Medicine.
The researchers followed a subset of subjects from a large cross-cultural study of dementia, called the Ni-Hon-Sea Project, which investigated Alzheimer’s disease and vascular dementia in older Japanese populations living in Japan, Hawaii and Seattle, Wash.
For the current study, called the Kame Project, the researchers identified 1,836 dementia-free subjects in the Seattle population and collected information on their dietary consumption of fruit and vegetable juices. They then assessed cognitive function every two years for up to 10 years.
After controlling for possible confounding factors like smoking, education, physical activity and fat intake, the researchers found that those who reported drinking juices three or more times per week were 76 percent less likely to develop signs of Alzheimer’s disease than those who drank less than one serving per week.
The benefit appeared particularly enhanced in subjects who carry the apolipoprotein E ÿ-4 allele, a genetic marker linked to late-onset Alzheimer’s disease – the most common form of the disease, which typically occurs after the age of 65.
A diet that cuts Alzheimer's risk probably cuts stroke and heart disease risk as well.
Researchers have found that vitamins C, E, and beta carotene do not provide a neuroprotective effect against Alzheimer's. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) also have been found to provide little or no benefit. The researchers behind this study suspected that perhaps polyphenols in foods provide benefit.
Dai began to suspect that another class of antioxidant chemicals, known as polyphenols, could play a role. Polyphenols are non-vitamin antioxidants common in the diet and particularly abundant in teas, juices and wines. Most polyphenols exist primarily in the skins and peels of fruits and vegetables. Recent studies have shown that polyphenols (like resveratrol in wine) extend maximum lifespan by 59 percent and delay age-dependent decay of cognitive performance in animal models.
"Also, animal studies and cell culture studies confirmed that some polyphenols from juices showed a stronger neuroprotective effect than antioxidant vitamins. So we are now looking at polyphenols," Dai said.
The researchers intend to check blood polyphenol levels to see if high polyphenols correlate with low Alzheimer's risk.
The nomenclature here may seem confusing. Catechins in tea are both polyphenols and flavonoids. Polyphenols are a larger set of chemical compounds which includes flavonoids as a subset. Then within the subset called flavonoids exists the smaller subset catechins. Fruits have flavonoids called anthocyanins. Tea and wine (and presumably dark grape juice) contain flavonoids called catechins.
Obvious question: Was the protective effect against Alzheimer's seen in this study due to catechins from tea and grape juice or from anthocyanins found in fruits? Or perhaps from other flavonoids called flavones and flavonols? Or other polyphenols? Or some combination of the above? I'm sorry I do not have an answer for you.
One obvious question: Drink the juice or eat whole fruits and vegetables? Well, juices appear to work (see above) and are quicker to consume. But perhaps the people who consume more fruit and vegetable juices also eat more fruits and vegetables. It is not clear what confounding factors these researchers controlled for.
Writing in the article, Qi Dai, MD, PhD, states, “We found that frequent drinking of fruit and vegetable juices was associated with a substantially decreased risk of Alzheimer’s disease. This inverse association was stronger after adjustments for potential confounding factors, and the association was evident in all strata of selected variables. These findings are new and suggest that fruit and vegetable juices may play an important role in delaying the onset of Alzheimer’s disease”.
I find it really surprising that these researchers could find an influence from juices above the background of all the other factors that will influence polyphenol content of diet.
Enormous amounts of other research has been done on the health benefits of polyphenols including flavonoids. Green tea catechins might reduce the risk of prostate cancer.
Anaheim, Calif. – After a year's oral administration of green tea catechins (GTCs), only one man in a group of 32 at high risk for prostate cancer developed the disease, compared to nine out of 30 in a control, according to a team of Italian researchers from the University of Parma and University of Modena and Reggio Emilia led by Saverio Bettuzzi, Ph.D.
...
The 600 mg-per-day dosage of caffeine-free, total catechins (50 percent of which is EGCG) given to participants in the Italian study is one or two times the amount of green tea consumed daily in China, where ten to 20 cups a day is normal.
I do not want to drink 10, let alone 20, cups of green tea a day. I'd rather take some caffeine-free catechin capsules. Better yet, I'd rather figure out which fruits and vegetables would deliver the same benefits and eat them instead.
Green tea is very popular in Japan and its consumption there might be the cause of lower Alzheimer's in Japanese in Japan as compared to Japanese in America.
Another paper which reported a reduction in blood plasma peroxide free radicals with green tea extract found a higher concentration of catechin polyphenols per cup of green tea.
"We believe we have shown for the first time the course change of both green tea catechin levels in human plasma as well as human plasma lipid peroxide levels after oral green tea catechin supplementation, " said Teruo Miyazawa, Ph.D., biodynamic chemistry professor at the Tohoku University Graduate School of Life Science and Agriculture and the study's principal investigator.
...
In the study, 18 healthy male subjects between the ages of 23 and 41 ingested green tea extracts in tablet form (including 254 milligrams of catechins per subject - one cup of green tea contains about 100 to 150 milligrams of catechin). All of the subjects avoided tea and tea-related beverages for 12 hours prior to the testing. Blood samples were taken one hour before and after the catechin ingestion.
I'd love to see a massive comparison study of a wide range of fruits and vegetables, juices, teas, and cocoa (which also contains catechins) where the effects of each food on blood plasma peroxides, blood pressure, and other indicators were compared. What are the most potent foods to eat?
Black tea was found to be the biggest source of catechin polyphenols among elderly Dutch men.
The 806 male participants, averaging age 71 in 1985, were followed until 1995, with complete dietary and medical examinations in 1985 and 1990. Epidemiological evaluation of the health effects of catechins has previously been difficult due to the lack of information on the exact catechin composition of foods. For this study, the authors measured the catechin content of 120 frequently consumed plant foods, using the data to divide the subjects into low, medium and high quintiles of catechin consumption.
Among the men in the highest quintile, 87% of catechins in the diet came from black tea; whereas those in lower quintiles ate more foods in which catechins were less concentrated. High catechin intake was associated with other practices characteristic of a healthy lifestyle, such as refraining from smoking, eating more fruits and vegetables, and increased activity levels.
For examples of more on the health benefits of tea see these research reports: Tea Intake Is Inversely Related to Blood Pressure in Older Women and Black and Green Tea Polyphenols Attenuate Blood Pressure Increases in Stroke-Prone Spontaneously Hypertensive Rats.
Green tea is hardly the only food that can improve blood flow and reduce blood free radicals. For example, see the research paper: Wine Polyphenols Decrease Blood Pressure, Improve NO Vasodilatation, and Induce Gene Expression. The "NO" in the title refers to Nitric Oxide which is a naturally occurring vasodilator (i.e. it makes blood vessels widen which lowers blood pressure). Nitric oxide deficiency is, in all likelihood, a cause of high blood pressure. Some drugs release NO as their mechanism of action. Viagra and Cialis work by releasing NO to cause blood to flow in the right places for male sexual function. Minoxidil, the anti-hair loss drug, has the "nox" in its name because it too is an NO releaser. But better to raise your vascular NO by diet before resorting to drug use. The foods that'll improve NO will also deliver other benefits.
NEW YORK August 24, 2006 -- Researchers at Columbia University Medical Center have successfully restored normal memory and synaptic function in mice suffering from Alzheimer's disease. The study was published today on the website of the journal Cell.
Scientists at Columbia's Taub Institute for Research on Alzheimer's Disease and the Aging Brain have identified an enzyme that is required for normal cognition but that is impaired in a mouse model of Alzheimer's. They discovered that mice regained the ability to form new memories when the enzyme's function was elevated.
The research suggests that boosting the function of this enzyme, known as ubiquitin C-terminal hydrolase L1 (Uch-L1), may provide a promising strategy for battling Alzheimer's disease, and perhaps reversing its effects.
In the new study, the Columbia researchers discovered that the enzyme Uch-L1 is part of a molecular network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. By increasing Uch-L1 levels in mice that had Alzheimer's, they were able to improve the animals' ability to create new memories.
"Because the amyloid beta proteins that cause Alzheimer's may play a normal, important physiological role in the body, we can't destroy them as a therapy," explained Ottavio Arancio, M.D., Ph.D., Assistant Professor of Pathology at Columbia University Medical Center and co-principal investigator of the study with Michael Shelanski, MD, Ph.D., Chairman of the Department of Pathology at the Columbia University College of Physicians and Surgeons. "What makes this newly discovered enzyme exciting as a potentially effective therapy is that it restores memory without destroying amyloid beta proteins."
We'll have effective cures for Alzheimer's before cancer becomes totally curable. Alzheimer's is an easier problem.
The Uch-L1 prevents a harmful consequence of too much beta amylod.
"While amyloid beta is certainly a key player in Alzheimer's disease--and efforts to reduce it remain a worthy goal--our results show that, even in the presence of the plaque, damage to memory can be reversed."
The findings suggest that neurons' protein-ridding machinery, the so-called ubiquitin/proteasomal pathway, may play an important early role in the pathogenesis of Alzheimer's disease, he added.
Ubiquitin is a "tag" that marks proteins for destruction by the cellular "garbage disposal" known as the proteasome, Shelanski explained. Uch-L1 acts as the proteasome's "gatekeeper," he added. Before proteins can be eliminated by the proteasome, Uch-L1 must remove their ubiquitin tag.
Earlier studies found that the brains of Alzheimer's disease patients show an accumulation of ubiquitin-tagged proteins, suggesting some defect of the protein degradation machinery, the researchers noted. Studies of the brains of humans with Alzheimer's after death found evidence that the proteasome remained intact but largely unable to degrade proteins.
Interestingly, Uch-L1--a protein found almost exclusively in nerve cells--was also found at reduced levels in the Alzheimer's brain. Unpublished studies by Shelanski's group found that cells treated with Aß exhibited a rapid drop in Uch-L1, he said.
Uch-L1 doesn't sound like it stops the underlying cause of Alzheimer's. But if boosting it delays Alzheimer's disease progression drugs that boost Uch-L1 will buy Alzheimer's sufferers valuable time while treatments are devised that fix the underlying causes of the disease.
We need gene therapies that will rejuvenate the mechanisms which brain cells use to break down and remove proteins that are no longer needed. The aging of junk removal mechanisms probably leads to accumulation of junk in and around cells. That junk causes damage to cells and interferes with their operations and communications.
Development of treatments to improve intracellular and extracellular junk removal are two of the rejuvenation Strategies for Engineered Negligible Senescence (SENS).
Old brains can't take out the trash.
LA JOLLA, CA - Like most neurodegenerative diseases, Alzheimer's disease usually appears late in life, raising the question of whether it is a disastrous consequence of aging or if the toxic protein aggregates that cause the disease simply take a long time to form.
Now, a collaboration between researchers at the Salk Institute for Biological Studies and the Scripps Research Institute shows that aging is what's critical. Harmful beta amyloid aggregates accumulate when aging impedes two molecular clean-up crews from getting rid of these toxic species.
This finding opens the door for development of drugs preventing build-up of toxic protein aggregates in the brain. The study appears in the Aug. 10 issue of Science Express, the advanced online edition of the journal Science.
Biogerontologist Aubrey de Grey has repeatedly made the argument that biomedical science could do more to reduce death from assorted diseases of old age by reversing aging than by researching treatments for each disease. This paper provides evidence for his assertion. If brain cells could be rejuvenated they'd once more break down toxic proteins as well as they did when they were younger. Then the incidence of Alzheimer's diease would plummet.
The clearing out of beta amyloid protein fragments becomes less efficient as we age.
Throughout life, brain cells produce aggregation-prone beta-amyloid fragments that must be cleared. "This process is very efficient when we are young but as we get older it gets progressively less efficient," says Cohen. As the affected individual reaches the seventh decade of life the clearance machineries fail to degrade the continually forming toxic aggregates and the disease emerges. In individuals who carry early onset Alzheimer's-linked mutation, an increased "aggregation challenge" leads to clearance failure and the emergence of Alzheimer's much earlier – usually during their fifth decade.
Drugs that block steps in the formation of beta amyloid protein fragments might help. But we'd be better if we could get brain cells to once again effectively taking out the trash. We need Strategies for Engineered Negligible Senescence.
Old hippies who haven't toked for decades might come back to the stoner life. Marijuana active ingredient tetrahydrocannabinol blocks the formation of beta amyloid plaques which are suspected as a cause of Alzheimers disease.
LA JOLLA, CA, August 9, 2006 - Scientists at The Scripps Research Institute have found that the active ingredient in marijuana, tetrahydrocannabinol or THC, inhibits the formation of amyloid plaque, the primary pathological marker for Alzheimer's disease. In fact, the study said, THC is "a considerably superior inhibitor of [amyloid plaque] aggregation" to several currently approved drugs for treating the disease.
The study was published online August 9 in the journal Molecular Pharmaceutics, a publication of the American Chemical Society.
According to the new Scripps Research study, which used both computer modeling and biochemical assays, THC inhibits the enzyme acetylcholinesterase (AChE), which acts as a "molecular chaperone" to accelerate the formation of amyloid plaque in the brains of Alzheimer victims. Although experts disagree on whether the presence of beta-amyloid plaques in those areas critical to memory and cognition is a symptom or cause, it remains a significant hallmark of the disease. With its strong inhibitory abilities, the study said, THC "may provide an improved therapeutic for Alzheimer's disease" that would treat "both the symptoms and progression" of the disease.
The development of better tests for amyloid plaque formation probably will provide the ability to predict the development of Alzheimer's many years in advance of obvious symptoms. For people who face the threat of losing their memory 10 years hence if THC can prevent or delay that outcome use of THC might be worth it. Though quite a few people won't want to go through every day of their lives high on THC.
THC works better than commercial drugs currently on the market.
"When we investigated the power of THC to inhibit the aggregation of beta-amyloid," Janda said, "we found that THC was a very effective inhibitor of acetylcholinesterase. In addition to propidium, we also found that THC was considerably more effective than two of the approved drugs for Alzheimer's disease treatment, donepezil (Aricept ®) and tacrine (Cognex ®), which reduced amyloid aggregation by only 22 percent and 7 percent, respectively, at twice the concentration used in our studies. Our results are conclusive enough to warrant further investigation."
Alzheimer's is a terrible disease. It gradually robs you of your identity. People who face the prospect of losing their memories should be allowed a great deal of latitutde in terms of what they can do to protect themselves from that fate. I expect drugs, antibodies, and vaccines will all come to market in the next 10 years that stop and reverse beta amyloid plaque formation. Use of THC for this purpose will be transitory at best. But will any government even allow clinical trials of its effectiveness against Alzheimer's?
Apple juice improved brain function in mice genetically engineered to get Alzheimers Disease.
Animal research from the University of Massachusetts Lowell (UML) indicates that apple juice consumption may actually increase the production in the brain of the essential neurotransmitter acetylcholine, resulting in improved memory.
Neurotransmitters such as acetylcholine are chemicals released from nerve cells that transmit messages to other nerve cells. Such communication between nerve cells is vital for good health, not just in the brain, but throughout the body.
“We anticipate that the day may come when foods like apples, apple juice and other apple products are recommended along with the most popular Alzheimer’s medications,” says Thomas Shea, Ph.D., director of the UML Center for Cellular Neurobiology and Neurodegeneration Research.
The study will be published in the August issue of the international Journal of Alzheimer’s Disease. The abstract is now available online at http://www.j-alz.com/issues/9/vol9-3.html.
I'd like to see experiments like this one repeated with a wider range of fruits and vegetables at a range of doses to identify the foods that deliver the most benefit the least amount of calories consumed. Also, use of quercetin, other flavonoids, and other antioxidants by themselves would help tease out which compounds are delivering the benefits.
In this novel animal study at UML, adult (9-12 months) and old (2-2.5 years) mice, some specially bred to develop Alzheimer’s-like symptoms, were fed three different diets (a standard diet, a nutrient-deficient diet, and a nutrient-deficient diet supplemented with apple components (in this case, apple juice concentrate was added to their drinking water).
Among those fed the apple juice-supplemented diet, the mice showed an increased production of acetylcholine in their brains. Also, after multiple assessments of memory and learning using traditional Y maze tests, researchers found that the mice who consumed the apple juice-supplemented diets performed significantly better on the maze tests.
Diet optimization for aging brains could provide great personal and economic benefits for hundreds of millions of people.
Apple juice provided acetylcholine benefit to both Alzheimer's mice and to aged normal mice.
In fact, the normal adults had the same acetylcholine levels regardless of diet.
However, the genetically engineered mice on the nutrient-poor diet had lower acetylcholine levels. But this drop was prevented in those given apple juice.
In the aged mice on a normal diet, acetylcholine levels were lower than in the normal adult mice; and their levels were even lower if placed on the nutrient-poor diet. But, again, this decline was prevented by the addition of apple juice to drink.
Eat apple sauce with your salmon dinner.
Update: Elderly people in Singapore who occasionally consume curry score higher on a standard test of cognitive function. The turmeric in curry and, in particular, the curcumin in the turmeric might be behind this effect. Those who benefitted did not even have to eat it once a month. Just occasional consumption is enough to produce a measurable benefit.
Building on their discovery that people with Alzheimer’s have ß-amyloid deposits that appear as unusual cataracts in the lens of the eye, Lee E. Goldstein, M.D., Ph.D., of Brigham & Women's Hospital and Harvard Medical School, Boston, and colleagues have developed a new, non-invasive, laser technology that may detect Alzheimer’s at its earliest stages.
Clumps of abnormal ß-amyloid protein (known as “plaques”) accumulate outside the brain’s nerve cells in people with Alzheimer’s. As Goldstein and colleagues previously reported in the British medical journal The Lancet, these same ß-amyloid clumps also collect in the lens of the eye as unusual “supranuclear cataracts.” These Alzheimer’s cataracts are different from common, age-related cataracts. This is the first evidence to date that Alzheimer’s-related amyloid pathology may occur outside the brain.
In their most recent experiments to be reported in Madrid, the researchers used genetically engineered Alzheimer’s mice to test a new, non-invasive molecular diagnostic technology. Goldstein and his team directed a brief pulse of infrared light – barely visible to humans – into the eye of each of four non-anesthetized Alzheimer mice and four age-matched normal mice every month starting at five months of age. Analysis of how the light bounced back from the lens completely separated the two types of mice by 10 months of age, when amyloid lesions were not detectable in the brain or eye by conventional means. The scientists believe that this technology, known as quasi-elastic light scattering (QLS), may detect the very earliest stages of ß-amyloid pathology, even in eyes that are completely clear.
“Amyloid in the lens can be detected using extremely sensitive, non-invasive optical techniques. This makes the lens an ideal window for early detection and disease monitoring in Alzheimer’s,” Goldstein said.
Early identification of developing Alzheimer's might extend back by literally decades the point at which a person can be diagnosed as developing Alzheimer's. Imagine being told at, say, age 45 that 20 or 25 years from now your memory will degrade far enough that you'll have clincal Alzheimer's. I hope such people so diagnosed will react by making loud demands of their elected officials (or the dictators who rule them as the case may be) to accelerate the development of treatments. People should treat early diagnosis as a wake-up call to become politically active and fight for much larger efforts to discover the causes and cures of their diseases.
Early diagnosis will also greatly speed up research on preventive therapies, whether those therapies be drugs, diet, or other techniques. Long longitudinal studes that watch for increased risks of diseases will be replaced by shorter studies that can watch people for several years to see what factors are associated with very early stage development of Alzheimer's and other diseases of aging. Also, people so diagnosed will be able to try new therapies and scientists will be able to find out whether each therapy works before memory has degraded by a substantial amount.
The article linked to above also reports on an fMRI (functional magnetic resonance imaging) technique that finds small blood vessel ruptures may cause dementia in the elderly. Better measurement methods for this problem will lead to better ways to test therapies in shorter periods of time.
Update: Once you get the diagnosis of very early stage Alzheimer's Disease you'll of course want an immediate cure before the brain deteriorates much. Well, some Australian researchers might have the ticket. A drug called PBT2 might stop and reverse the build-up of the plaque that probably causes Alzheimer's.
Professor Ashley Bush, MD, PhD, of the Mental Health Research Institute of Victoria (Australia) and co-founding scientist of Prana Biotechnology Limited (Nasdaq: PRAN, ASX: PBT) today presented data at the 10th International Conference on Alzheimer's Disease (ICAD) in Madrid demonstrating that in mouse models[1] PBT2:
-- improved memory performance within five (5) days of oral dosing
-- rapidly reduced the levels of soluble beta-amyloid ("Abeta") in the brain, and
-- restored normal function to Abeta impaired synapses.
I'm expecting cures for Alzheimer's before cures for cancer. Preventing the build-up of a protein plaque seems a lot easier than stopping some of your own cells from dividing like mad.
The results sound promising.
In addition, Professor Bush referenced studies he and colleagues performed on 15-month old transgenic Alzheimer's mice treated with 30 mg/kg PBT2, which showed the drug reduced soluble Abeta40 and Abeta42 levels by 60 percent within 24 hours of oral PBT2 administration. Professor Bush also presented mechanistic findings showing that PBT2 blocks the copper-dependent formation of amyloid oligomers, considered by many to be the toxic chemical entity leading to brain damage in Alzheimer's disease. Professor Bush showed that, by this mechanism, PBT2 in the rodent brain blocks synaptotoxicity caused by soluble beta-amyloid oligomers and restores LTP (long-term potentiation) -- the neuronal electrical activity that underlies memory formation.
Another team has just reported preliminary results of a monoclonal antibody against Alzheimer's plaques. Drugs, vaccines, and monoclonal antibodies will all work against Alzheimer's eventually. We'd already have vaccines against Alzheimer's if the US Food and Drug Administration didn't demand excessively low levels of side effects. I'd rather run the risk of brain inflammation from a vaccine if I knew I was in the process of losing my memory and ability to think. But the FDA doesn't think we should be allowed to judge such trade-offs for ourselves.
Overall, each additional unit of the Mediterranean diet adherence score (a zero to nine-point scale) was associated with a 9% to 10% decreased risk for Alzheimer's, reported Nikolaos Scarmeas, M.D., of Columbia University here, and colleagues, in the April issue of the Annals of Neurology and published online.
Compared with participants who had the lowest adherence to the diet, the risk for those with the highest adherence was 39% to 40% lower, while those in the middle tertile had a decreased Alzheimer's risk of 15% to 21%. This, the investigators said, showing a significant dose response, and sensitivity analysis did not change these findings.
The result comes from a diet study of elderly people.
Scarmeas followed more than 2,000 cognitively normal elderly people from Manhattan, with an average age of 77 years, for about four years. Every 18 months the participants filled out a dietary questionnaire asking them about what they consumed and how often. In total, 262 of the participants developed Alzheimer's during the course of the study.
The changes that lead to Alzheimer's start happening decades before the full blown disease. Therefore following a better diet makes sense even if you are fairly young.
A new UCLA imaging study shows that age-related breakdown of myelin, the fatty insulation coating the brain's internal wiring, correlates strongly with the presence of a key genetic risk factor for Alzheimer disease.
The findings are detailed in the January edition of the peer-reviewed journal Archives of General Psychiatry and add to a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life.
In addition, the study demonstrates how genetic testing coupled with non-invasive evaluation of myelin breakdown through magnetic resonance imaging (MRI) may prove useful in assessing treatments for preventing the disease.
The idea of losing the insulation of the nerves of one's brain with aging strikes me as thoroughly disgusting. We should heavily fund attempts to develop treatments to prevent and reverse brain aging.
A genetic variation in Apolipoprotein E causes the myelin insulating sheaths to break down more rapidly with age.
As the brain continues to develop in adulthood and as myelin is produced in greater and greater quantities, cholesterol levels in the brain increase and eventually promote the production of a toxic protein that attacks the brain. The protein attacks myelin, disrupts message transfer through the axons and eventually can lead to the brain/mind-destroying plaques and tangles visible years later in the cortex of Alzheimer patients.
The Apolipoprotein E (ApoE) genotype is the second most influential Alzheimer risk factor, after only advanced age. The study used MRI to assess myelin breakdown in 104 healthy individuals between ages 55 and 75 and determine whether the shift in the age at onset of Alzheimer disease caused by the ApoE genotype is associated with age-related myelin breakdown.
The results show that in later-myelinating regions of the brain, the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.
Some people argue that aging is a natural process or a sacred process which we can experience with dignity. But where's the dignity of suffering from a progressive breakdown of the insulation on the nerves of your brain? One doesn't just become gray and wrinkly and move more slowly with age. One's brain goes. One loses the ability to think as well. One is more prone to confusion, less able to deal with the problems of life, less able to recall memories of past events or to remember what one has to accomplish on any given day. There's nothing the least bit dignified about brain decay. It does not bring wisdom. It takes away the ability to recall lessons learned.
Brain PET scans of the brain's hippocampus analysed with new software can predict who will get Alzheimer's Disease at least 9 years in advance. (same article here)
New York University School of Medicine researchers have developed a brain scan-based computer program that quickly and accurately measures metabolic activity in a key region of the brain affected in the early stages of Alzheimer's disease. Applying the program, they demonstrated that reductions in brain metabolism in healthy individuals were associated with the later development of the memory robbing disease, according to a new study.
"This is the first demonstration that reduced metabolic activity in the hippocampus may be used to help predict future Alzheimer's disease," says Lisa Mosconi, Ph.D., a research scientist in the Department of Psychiatry, who developed the computer program and led the new study. "Although our findings need to be replicated in other studies," she says, "our technique offers the possibility that we will be able to screen for Alzheimer's in individuals who aren't cognitively impaired."
How would you like to get a brain scan and then be told that in 5 or 10 years you will start to lose your memory and eventually forget everything thing you know?
Dr. Mosconi and colleagues have recently published the technical details of the program, called "HipMask," in the June 2005 issue of the journal Neurology. She will present the new findings on June 20 at the Alzheimer's Association International Conference on Prevention of Dementia held in Washington.
The computer program is an image analysis technique that allows researchers to standardize and computer automate the sampling of PET brain scans. The NYU researchers hope the technique will enable doctors to measure the metabolic rate of the hippocampus and detect below-normal metabolic activity.
The technique grew out of years of research by Mony de Leon, Ed.D., Professor of Psychiatry and Director of the Center for Brain Health. His group was the first to demonstrate with CT and later with MRI scans that the hippocampus, a sea-horse shaped area of the brain associated with memory and learning, diminishes in size as Alzheimer's disease progresses from mild cognitive impairment to full-blown dementia.
Yet until now there has been no reliable way to accurately and quickly measure the hippocampal area of the brain on a PET scan. The hippocampus is small and its size and shape are affected greatly in individuals with Alzheimer's, making it difficult to sample this region. HipMask is a sampling technique that uses MRI to anatomically probe the PET scan.
MRI relies on electromagnetic energy to excite water molecules in the brain to create an anatomical map of the brain. The MRI was used in the study to determine the total volume of the hippocampus and then to define that portion (namely the HipMask) that was shared by all persons regardless of their disease status. PET employs radioactively labeled glucose to show the brain at work and the HipMask was applied to these scans to derive estimates of the hippocampal glucose metabolism.
The researchers followed 53 healthy, normal subjects between the ages of 54 and 80 for at least 9 years and in some cases for as long as 24 years. All subjects received two FDG-PET scans -- one at baseline and a follow-up after 3 years. Thirty individuals had a second follow-up scan after another seven years. Altogether there were 136 PET scans.
The researchers applied the HipMask to all 136 scans. The results showed that hippocampal glucose metabolism, as determined by the HipMask, was significantly reduced 15% to 40% on the first scan, compared to controls, of those 25 individuals who would later experience cognitive decline related to either mild cognitive impairment or to Alzheimer's. The researchers found that the baseline hippocampal glucose metabolism was the only brain or clinical measure that predicted the future cognitive decline.
"Right now, we can show with great accuracy who will develop Alzheimer's nine years in advance of symptoms, and our projections suggest we might be able to take that out as far as 15 years," says Dr. de Leon, whose longitudinal study is funded by the National Institutes of Health (NIH).
"Our basic results will need to be replicated in other studies and expanded to include PET data from diverse patient groups," adds Dr. De Leon. "But we're confident this is a strong beginning, demonstrating accurate detection of early Alzheimer's disease. Now we have a better tool to examine disease progression, and we anticipate this might open some doors to prevention treatment strategies."
Most people are not going to get brain PET scans. The greater value of this finding is in research on methods to prevent or delay the onset of Alzheimer's Disease.
Don't wait for that PET scan result to come back with bad news. Reduce your risk of Alzheimers.
People who drink fruit or vegetable juice at least three times a week seem four times less likely to develop Alzheimer's than nonjuice drinkers, according to a study of 1,800 elderly Japanese Americans. The theory is that juice contains high levels of polyphenols, compounds that may play a brain-protective role.
Less education, gum disease early in life, or a stroke were more important than genes in determining who got dementia, concluded a study of 100 dementia patients with healthy identical twins. Education stimulates neuronal growth; gum disease is a marker of brain-harming inflammation.
Exercise and moderate alcohol consumption also appear to lower the risk of Alzheimer's Disease.
Middle-aged sons and daughters of people with Alzheimer's disease may be able to reduce their risk of getting the disorder through lifestyle measures such as exercise, avoiding gum disease, moderate alcohol consumption, and drinking fruit and vegetable juice, according to new research.
Keep your teeth clean. Drink some V-8 or pure fruit juice. Get regular exercise. They'll all protect your brain.
Update: Periodontal disease increases the risk of Alzheimer's.
A new study of dementia in identical twins suggests that exposure to inflammation early in life quadruples one's risk of developing Alzheimer's disease.
Margaret Gatz, lead author and professor of psychology in the USC College of Letters, Arts and Sciences, is slated to present her findings at the first Alzheimer's Association International Conference on Prevention of Dementia, to be held June 18-21 in Washington, D.C.
If confirmed, the link would add inflammatory burden to the short list of preventable risk factors for Alzheimer's.
Previous studies by Gatz and others have shown that Alzheimer's is strongly genetic: If one twin has the disease, his or her identical twin has a 60 percent chance of developing it.
Stroke and a short period of formal education both increase the odds of dementia, but not of Alzheimer's specifically, the new study found.
Dementia is an umbrella term for many conditions, including Alzheimer's.
"People can plan a life span that will alter dementia risk," Gatz said. "And these aren't risk factors that are unique to dementia. Many of these are also risk factors for other disorders. This is good news."
Gatz's team, which included researchers from the Karolinska Institute in Stockholm, Sweden, sifted the 20,000 participants in the Swedish Twin Registry for the 109 "discordant" pairs where only one twin had been diagnosed with dementia.
Information about participants' education, activities and health history came from surveys they completed in the 1960s, when the registry was created, and from hospital discharge records.
The surveys included questions about loose or missing teeth. Gatz and colleagues used the answers to build a crude indicator of periodontal disease.
"We're talking about gum disease, but it was measured by teeth lost or loose," Gatz said. "It's not perfect. Given it's not perfect, it's even more striking that it's such a solid risk factor."
The conclusion is not that good oral health can prevent Alzheimer's, but that an inflammatory burden early in life, as represented by chronic gum disease, may have severe consequences later.
I think that previous sentence is poorly worded. Surely good oral health will reduce the risk of Alzheimer's. Poor oral health is not the only souce of inflammatory burden. But it is one big source.
Gatz was inspired to focus on inflammation by the work of USC gerontologists Caleb Finch and Eileen Crimmins, who published a paper in the journal Science linking today's record life spans to lower rates of childhood infectious diseases, such as gum disease, flu, rheumatic fever, tuberculosis and other illnesses.
Such diseases are often preventable, raising hope for prevention of Alzheimer's.
"If what we're indexing with periodontal disease is some kind of inflammatory burden, then it is probably speaking to general health conditions," Gatz said. "There was in our twins quite a lot of periodontal disease, and at that time in Sweden there was a lot of poverty."
The study, titled "Potentially Modifiable Risk Factors From Dementia: Evidence From Identical Twins," also found that mental activities at age 40, such as reading or attending cultural events, did not seem to lower the risk of developing Alzheimer's.
So crossword puzzles do not help. Then I guess writing a blog isn't going to help either. Heavy sigh.
Previous reports have suggested a link between education and lowered risk of Alzheimer's. But when education is controlled for by using twins with different levels of education then the education effect becomes very low. One possible explanation might be that level of education is a proxy for level of intelligence. Higher intelligence people might be more likely to avoid behaviors (like eating junk food or not practicing good dental hygeine) than lower intelligence people. Or perhaps having smarter brains allows a person to deteriorate for longer from a higher level of initial cognitive function before the effects of Alzheimer's become apparent.
Participants who had more education than their twins were at slightly lower risk of developing dementia, but the influence of education on Alzheimer's risk was statistically negligible.
"Once one controls for genes, the level of education is not a huge risk factor," said Gatz, who questioned popular attitudes linking Alzheimer's or dementia to mental inactivity.
Drinking soda leads to tooth decay. So if you don't want your kids to get Alzheimer's Disease in their old age then do not let them drink soda.
The human body has its own defense against brain aging: the innate immune system, which helps to clean the brain of amyloid-beta waste products. However, UCLA researchers discovered that some patients with Alzheimer's disease have an immune defect making it difficult to clean away these wastes. This may lead to over-saturation of the brain with amyloid beta, which form amyloid plaques, the definitive hallmark of Alzheimer's disease.
Published in the June 10 issue of the Journal of Alzheimer's Disease, the findings could lead to a new approach in diagnosing and treating Alzheimer's disease by helping to diagnose and correct this immune defect. This is the first time that researchers have discovered that the innate -- or more primitive -- part of the immune system may play a role in the development of Alzheimer's disease.
Using blood samples, investigators found that in healthy people, cells belonging to the innate immune system called macrophages, cleared amyloid-beta in a test tube test developed at UCLA. However, the macrophages of some Alzheimer's patients could not adequately perform this cleaning job.
"Macrophages are the janitors of the innate immune system, gobbling up waste products in the brain and throughout the body," said Dr. Milan Fiala, first author and UCLA researcher.
Fiala notes that there may be a problem either with the macrophages not effectively binding to amyloid beta or a problem in the absorption or uptake, which is called "phagocytosis." He adds that this immune defect may also be present in other diseases where a build-up of waste and plaques occur, such as in cardiovascular disease and Gaucher's disease.
"If further study shows that this defective macrophage function is present in most Alzheimer's disease patients, new hormonal or immune-boosting approaches may offer new approaches to treating the disease," adds Fiala.
Researchers add that this new approach differs from the amyloid-beta immunization method, which utilizes another part of the immune system called the adaptive immune system. According to Fiala, the immunization approach has resulted in amyloid-beta clearance in the lab in an animal model, but in a human clinical trial led to brain inflammation in a subset of patients.
In future studies, investigators plan to regulate the innate immune system by natural substances such as hormones, and natural products such as curcumin (from the curry powder). Currently in their lab, Fiala and Dr. George Bernard who is a professor in the UCLA Department of Oral Biology and Medicine,are testing the effectiveness of a naturally occurring hormone, called insulin-like growth factor I, in conjunction with a research team from the MP Biomedicals LLC Company.
This is a valuable piece of work. Perhaps immune system aging causes the innate immune system to fail to clear beta amyloid plaques. If so, restoring its proper function might turn out to be difficult because immune system rejuvenation might be necessary. Or perhaps a genetic difference causes the lower ability to remove the plaques. If so, perhaps a gene therapy could give the macrophages a capability that they lack.
Among the 7 Strategies for Engineered Negligible Senescence (SENS) to halting and rejuvenate bodies is the removal of accumulated extracellular junk. The amyloid plaque accumulations which likely cause Alzheimers are a form of extracellular junk and treatments to remove those plaques will likely be among the earliest rejuvenation treatments used in clinical practice. Because the amyloid plaques are associated with a major neurological disorder the development of means to remove them gets much more attention than some of the other SENS approaches. For example, little effort is going into the development of treatments to remove intracellular junk from lysosomes or to develop gene therapie