If this works as claimed then better to get the vitamin D decades before enough toxic junk proteins accumulate enough to cause clinical symptoms of brain damage. Vitamin D boosts removal of a protein that is the main component of Alzheimer's plaques.
A team of academic researchers has identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the main component of plaques associated with Alzheimer's disease.
Published in the March 6 issue of the Journal of Alzheimer's Disease, the early findings show that vitamin D3 may activate key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein.
Previous laboratory work by the team demonstrated that specific types of immune cells in Alzheimer's patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta. But the researchers didn't know how it worked.
"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer's disease," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.
If you need a technical reason to take vitamin D here it is:
Researchers found that in both Type I and Type II macrophages, the added 1a,25–dihydroxyvitamin D3 played a key role in opening a specific chloride channel called "chloride channel 3 (CLC3)," which is important in supporting the uptake of amyloid beta through the process known as phagocytosis. Curcuminoids activated this chloride channel only in Type I macrophages.
The scientists also found that 1a,25–dihydroxyvitamin D3 strongly helped trigger the genetic transcription of the chloride channel and the receptor for 1a,25–dihydroxyvitamin D3 in Type II macrophages. Transcription is the first step leading to gene expression.
What I wonder: does an aging immune system contribute to the development of Alzheimer's Disease and other diseases that are the result of accumulation of damaging compounds in the body? Once we can rejuvenate the immune system will the incidence of many diseases go down just because more trash will get taken out?
Immune system rejuvenation could cut death from flu and pneumonia in the aged. Also, the potential to cut the incidence of cancer with better immune systems is very real. Rare people have exceptional immune systems for fighting cancer and aged immune systems with shorter telomeres are associated with higher cancer risk.
The immune system, so accessible in the blood, will be easier to rejuvenate than organs. So the immune system might not be the first part of your body you might think you want to rejuvenate. But ease of access and potential for multiple benefits from rejuvenation puts the immune system on my short list of body systems I most want to rejuvenate.
Mitochondria are organelles within cells which break down sugar to release energy. Their healthy functioning is key to health. Accumulation of damage in mitochondria is suspected to contribute to aging. In at least some cases Parkinson's Disease is thought to be caused by damaged mitochondria.
Boston, Mass. - Current thinking about Parkinson's disease is that it's a disorder of mitochondria, the energy-producing organelles inside cells, causing neurons in the brain's substantia nigra to die or become impaired. A study from Children's Hospital Boston now shows that genetic mutations causing a hereditary form of Parkinson's disease cause mitochondria to run amok inside the cell, leaving the cell without a brake to stop them. Findings appear in the November 11 issue of Cell.
Mitochondrial movement is often a good thing, especially in neurons, which need to get mitochondria to cells' periphery in order to fuel the axons and dendrites that send and receive signals. However, arresting this movement is equally important, says senior investigator Thomas Schwarz, PhD, of Children's F.M. Kirby Neurobiology Center, since it allows mitochondria to be quarantined and destroyed when they go bad.
"Mitochondria, when damaged, produce reactive oxygen species that are highly destructive, and can fuse with healthy mitochondria and contaminate them, too," Schwarz says. "It's the equivalent of an environmental disaster in the cell."
Damaged mitochondria accumulate in us as we age. The ability to either repair or more reliably eject them would slow the aging process. Combined with other rejuvenation therapies treatments aimed at ridding us of damaged mitochondria will eventually enable us to reverse aging.
To the extent that Parkinson's is caused by damaged mitochondria that's actually good news for the rest of us who do not have Parkinson's. Why? Because Parkinson's provides motives for medical researchers to develop therapies targeting destruction or repair of toxic damaged mitochondria. Such therapies will be beneficial the rest of us. So future treatments developed to fix the root cause of Parkinson's will also help those without Parkinson's.
UCSF researchers find that when looking at brains using functional magnetic resonance imaging (fMRI) older brains interrupted from a task do a poorer job of resuming where they left off.
Scientists at the University of California, San Francisco have pinpointed a reason older adults have a harder time multitasking than younger adults: they have more difficulty switching between tasks at the level of brain networks.
Juggling multiple tasks requires short-term, or "working," memory – the capacity to hold and manipulate information in the mind for a period of time. Working memory is the basis of all mental operations, from learning a friend's telephone number, and then entering it into a smart phone, to following the train of a conversation, to conducting complex tasks such as reasoning, comprehension and learning.
"Our findings suggest that the negative impact of multitasking on working memory is not necessarily a memory problem, per se, but the result of an interaction between attention and memory,” said the senior author of the study, Adam Gazzaley, MD, PhD, UCSF associate professor of neurology, physiology and psychiatry and director of the UCSF Neuroscience Imaging Center.
Basically, after processing an interrupt and resuming an interrupted task older brains show they did a poorer job of restoring context. In software terms, their stack gets corrupted.
When the young and older adults were interrupted, their brains disengaged from a memory maintenance network and reallocated neural resources toward processing the interruption. However, the younger adults re-established connection with the memory maintenance network following the interruption and disengaged from the interrupting image. The older adults, on the other hand, failed both to disengage from the interruption and to reestablish the neural network associated with the disrupted memory.
This has obvious implications for workplaces: cut back on unnecessary interrupts. But this advice doesn't just apply to older workers. Everyone takes a hit from interrupts, the extent of the cost is just a matter of degree. The cost has been documented for software developers in DeMarco and Lister's book PeopleWare. Unfortunately, the book has not had much of an impact on management thinking.
If you can see an interrupt coming then it would make sense to jot down some thoughts about what you are thinking about at that moment. Such jottings could help you restore state more quickly once the interrupt is over. Or just maintain a more detailed list of what you are trying to accomplish in a given day. One needs the ability to isolate oneself to think thru bigger thoughts.
ST. PAUL, Minn. – High blood pressure is linked to memory problems in people over 45, according to research published in the August 25, 2009, print issue of Neurology®, the medical journal of the American Academy of Neurology.
The study found that people with high diastolic blood pressure, which is the bottom number of a blood pressure reading, were more likely to have cognitive impairment, or problems with their memory and thinking skills, than people with normal diastolic readings.
For every 10 point increase in the reading, the odds of a person having cognitive problems was seven percent higher. The results were valid after adjusting for other factors that could affect cognitive abilities, such as age, smoking status, exercise level, education, diabetes or high cholesterol.
You can get double bonus points if you take a blood pressure lowering drug. Also see my post ACE Inhibitor Blood Pressure Drugs Cut Risk Of Dementia.
Not all blood pressure drugs are equal in protection provided against brain function decline with age. The angiotensin-converting enzyme (ACE) inhibitors are better for the brain than other blood pressure reducing drugs. But not all ACE inhibitors are equal either. The centrally acting ACE inhibitors provide the benefit.
WINSTON-SALEM, N.C. – A particular class of medication used to treat high blood pressure could protect older adults against memory decline and other impairments in cognitive function, according to a newly published study from Wake Forest University School of Medicine.
Research suggests that some of the drugs classified as angiotensin-converting enzyme (ACE) inhibitors, specifically those types of ACE inhibitors that affect the brain by crossing the blood-brain barrier, may reduce inflammation that could contribute to the development of Alzheimer's disease, a major cause of dementia.
The study appears in the current issue of Archives of Internal Medicine.
"High blood pressure is an important risk factor for Alzheimer's disease and vascular dementia," said Kaycee Sink, M.D., M.A.S., lead author of the study, geriatrician and an assistant professor of internal medicine – gerontology. "Our study found that all blood pressure medications may not be equal when it comes to reducing the risk of dementia in patients with hypertension."
Inflammation as an agent of accelerated aging is a recurring theme in a lot of research on aging mechanisms. Dietary and drug factors that reduce inflammation tend to slow aging and lower disease risks.
ACE inhibitors that can cross the blood-brain barrier get into the brain and dampen inflammation.
The study found an association between taking centrally-active ACE inhibitors and lower rates of mental decline as measured by the Modified Mini-Mental State Exam, a test that evaluates memory, language, abstract reasoning and other cognitive functions. The research showed that participants who were exposed to ACE inhibitors that cross the blood-brain barrier saw an average 65 percent less cognitive decline per year of exposure compared to participants taking other blood pressure medications.
What I would like to know: For people who do not have high blood pressure (knock on wood) which drugs or dietary elements will best lower brain inflammation? Anyone have insights on this?
Non-centrally active ACE inhibitors definitely do not help.
Researchers also found that non-centrally active ACE inhibitors were associated with an increased risk of dementia and the people taking them were more likely to develop difficulty performing daily activities. Specifically, participants who, for three years, took ACE inhibitors that do not cross the blood-brain barrier were at a 73 percent greater risk of developing dementia than were the individuals taking other anti-hypertensive drugs.
Okay, those of you with high blood pressure are wondering: which ACE inhibitors are centrally acting? Here's your list:
Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).
Anyone going to get their high blood pressure drug changed as a result of this news?
Groucho Marx famously opined "I don't care to belong to any club that will have me as a member"". Well, here's one club I would like to join: the super memory club of people who do not lose their memory marbles as they grow old.
In recent years scientists have become intensely interested in what could be called a super memory club — the fewer than one in 200 of us who, like Ms. Scott and Ms. Cummins, have lived past 90 without a trace of dementia. It is a group that, for the first time, is large enough to provide a glimpse into the lucid brain at the furthest reach of human life, and to help researchers tease apart what, exactly, is essential in preserving mental sharpness to the end.
The scientists studying sharp elderly people suspect bridge playing and other mentally stimulating activity might be protective. But they are still trying to tease out the direction of causation. According to the researchers interviewed in the article diet and exercise seem to deliver little benefit. Your ability to slow your brain aging is limited. Though I expect anything that is good for cardiovascular health will help because if you can't get blood through your vascular system to the brain cells they'll wither and die.
Not surprisingly evidence points to genetic factors.
In studies of the very old, researchers in California, New York, Boston and elsewhere have found clues to that good fortune. For instance, Dr. Kawas’s group has found that some people who are lucid until the end of a very long life have brains that appear riddled with Alzheimer’s disease. In a study released last month, the researchers report that many of them carry a gene variant called APOE2, which may help them maintain mental sharpness.
Dr. Nir Barzilai of the Albert Einstein College of Medicine has found that lucid Ashkenazi Jewish centenarians are three times more likely to carry a gene called CETP, which appears to increase the size and amount of so-called good cholesterol particles, than peers who succumbed to dementia.
I expect the knowledge about CETP and cholesterol particles will lead to useful brain preserving treatments because it will be possible to do gene therapy and cell therapy to the liver to adjust its metabolism of cholesterol, lipids, and lipoproteins. Ditto APOE2 which is synthesized by the liver. I expect reengineering the liver to prevent artery clogging and to lower oxidative stress will slow the rate of brain aging. The liver seems like a great target for therapies aimed at slowing the aging process.
Slowed aging via liver bioengineering could provide us with more time to develop therapies that reverse the aging process.
It turns out there's a scientific reason why older people tend to see the past through rose-coloured glasses.
So then older people share something in common with Eric Idle nailed to a cross singing "Always look on the bright side of life".
A University of Alberta medical researcher, in collaboration with colleagues at Duke University, identified brain activity that causes older adults to remember fewer negative events than their younger counterparts.
"Seniors actually use their brain differently than younger people when it comes to storing memory, especially if that memory is a negative one," said study author Dr. Florin Dolcos, an assistant professor of psychiatry and neuroscience in the Faculty of Medicine & Dentistry.
The study, published online in December in the U.S.-based journal Psychological Science, found age-related changes in brain activity when participants with an average age of 70 where shown standardized images that depicted either neutral or strongly negative events.
The research team asked older and younger participants to rate the emotional content of these pictures along a pleasantness scale, while their brain activity was monitored with a functional magnetic resonance imaging (fMRI) machine, a high-tech device that uses a large magnet to take pictures inside the brain. Thirty minutes later, participants were unexpectedly asked to recall these images. The older participants remembered fewer negative images than the younger participants.
Brain scans showed that although both groups had similar activity levels in the emotional centres of the brain, they differed when it came to how these centres interacted with the rest of the brain.
The older participants had reduced interactions between the amygdala, a brain region that detects emotions, and the hippocampus, a brain region involved in learning and memory, when shown negative images. Scans also showed that older participants had increased interactions between the amygdala and the dorsolateral frontal cortex, a brain region involved in higher thinking processes, like controlling emotions. The older participants were using thinking rather than feeling processes to store these emotional memories.
The greater emotional reaction of younger people probably tends to elicit a bigger behavioral response from younger people. What I wonder: Is the change in the older response due to physical aging or accumulation of learning from experience?
Young adults used more of the brain regions typically involved in emotion and recalling memories.
"The younger adults were able to recall more of the negative photos," said Roberto Cabeza, Ph.D., senior author and Duke professor in the Center for Cognitive Neuroscience. If the older adults are using more thinking than feeling, "that may be one reason why older adults showed a reduction in memory for pictures with a more negative emotional content."
"It wasn't surprising that older people showed a reduction in memory for negative pictures, but it was surprising that the older subjects were using a different system to help them to better encode those pictures they could remember," said lead author Peggy St. Jacques, a graduate student in the Cabeza laboratory.
One of my questions about future rejuvenation therapies: How much will rejuvenated minds become youthful in their thought patterns and behavior? Some aspects of youthful function will be restored by rejuvenation. But other aspects might not. We might even need to choose among various youthful patterns of thinking to restore. Restore a stronger tendency to form negative memories? Restore more intense reactions of anger, sadness, or other emotions?
Long time readers know I've argued that the brain is most problematic for rejuvenation because it must be repaired rather than replaced. It is very complex. Repair will be extremely difficult. But the difficulty of brain rejuvenation doesn't just flow from the complexity, size, and need to repair billions of individual cells. We also face the difficult question of deciding which sorts of age-related brain changes to reverse and which to leave in their changed older patterns of functioning.
If you do not exercise much is there any amount of scientific evidence that will get you off your duff? Maybe not. But if you do exercise regularly here is another reason to feel satisfied with yourself for getting enough exercise.
"Our results show that exercise may reduce age-related changes in brain vasculature and blood flow," said presenter Feraz Rahman, M.S., currently a medical student at Jefferson Medical College in Philadelphia. "Other studies have shown that exercise prevents cognitive decline in the elderly. The blood vessel and flow differences may be one reason."
The researchers recruited 12 healthy adults, age 60 to 76. Six of the adults had participated in aerobic exercise for three or more hours per week over the last 10 years, and six exercised less than one hour per week. All of the volunteers underwent MRI to determine cerebral blood flow and MR angiography to depict blood vessels in the brain.
Using a novel method of three-dimensional (3-D) computer reconstruction developed in their lab, the researchers were able to make 3-D models of the blood vessels and examine them for shape and size. They then compared the blood vessel characteristics and how they related to blood flow in both the active and inactive groups.
The results showed that the inactive group exhibited fewer small blood vessels in the brain, along with more unpredictable blood flow through the brain.
I could tell you that eating more fruits and vegetables will slow your brain aging. But you already know that.
In the Baycrest study, 12 younger adults (average age 26) and 12 older adults (average age 70) took part in a face recognition task that involved having their brains scanned with fMRI while they were shown pictures of faces and later again when trying to recall whether they'd seen each face before. Researchers found that when younger and older adults had difficulty encoding a new memory (certain face), this was marked by decreased activity in brain regions important for encoding, such as the hippocampus. The researchers weren't surprised by this based on an abundance of scientific evidence indicating the importance of hippocampus for making memories.
But the older brains showed additional increased activation in certain regions during memory encoding failure that was not found in younger brains!
"The older brains showed increased activation in certain regions that normally should be quieter or tuned down," said Dale Stevens, who led the study as a psychology graduate at Baycrest's Rotman Research Institute, with senior scientists Drs. Cheryl Grady and Lynn Hasher, both of whom are distinguished researchers in aging, memory, attention and distraction.
"The auditory cortex and prefrontal cortex, which are associated with external environmental monitoring, were idling too high. The older brains were processing too much irrelevant information from their external environment – basically the scanner noise," said Dr. Stevens, who is now a post-doctoral fellow in the Department of Psychology and Cognitive Neuroscience at Harvard University. The younger brains did not show this abnormal high idling during their failed memory encoding.
The practical take-home lesson here: As you get older cut back on environmental distractions when you need to concentrate.
Another take-home lesson for employers: Cubicles are especially productivity draining for older employees. The noise and distractions of unwalled workplaces exact a greater cost in lost productivity as your employees age. Put up some sound-deadening walls and increase profits.
The better solution we need: brain rejuvenation therapies. We need remyelination to restore the neuron insulation which deteriorates with age.
Muscle exercise might be good for your brain. Exercise boosts brain stem cell generation in both middle-aged and young mice.
BETHESDA, Md. (Nov. 18, 2008) − A new study confirms that exercise can reverse the age-related decline in the production of neural stem cells in the hippocampus of the mouse brain, and suggests that this happens because exercise restores a brain chemical which promotes the production and maturation of new stem cells.
The researchers trained young (3 months), adult (7 months), early middle-aged (9 months), middle-aged (13 months) and old (24 months) mice to run a treadmill for up to one hour a day.
The study tracked neurogenesis, age, exercise, serum corticosterone levels and brain-derived neurotrophic factor (BDNF) and its receptor TrkB levels in the hippocampus. The researchers focused on middle age as a critical stage for the decline of neurogenesis in the mice.
As expected, the study found that neurogenesis drops off sharply in middle-aged mice. For example, the number of neural progenitor and mitotic (dividing) cells in the hippocampus of middle-aged mice was only 5% of that observed in the young mice.
The researchers also found that exercise significantly slows down the loss of new nerve cells in the middle-aged mice. They found that production of neural stem cells improved by approximately 200% compared to the middle-aged mice that did not exercise. In addition, the survival of new nerve cells increased by 170% and growth by 190% compared to the sedentary middle-aged mice. Exercise also significantly enhanced stem cell production and maturation in the young mice. In fact, exercise produced a stronger effect in younger mice compared to the older mice.
What I wonder: once we can replace aged neural stem cells with younger stem cells will we hit a problem with excessive crowding of neurons and other brain cells as the reproduction of neural stem cells uses up all available space?
Some people experience slower brain aging. Are you one of the lucky ones?
Now they have a preliminary answer. Scientists examined the brains of five deceased people considered super aged because of their high performance on memory tests when they were more than 80 years old and compared them to the brains of elderly, non-demented individuals. Researchers found the super aged brains had many fewer fiber-like tangles than the brains of those who had aged normally. The tangles consist of a protein called tau that accumulates inside brain cells and is thought to eventually kill the cells. Tangles are found in moderate numbers in the brains of elderly and increase substantially in the brains of Alzheimer's disease patients.
These results suggest that treatments for Alzheimer's disease that aim to prevent tangle formation will provide benefit to all people as their brains age. That's good news. A lot of effort is going into Alzheimer's treatment and the treatment development efforts aimed at tangles strike me as having a good chance of succeeding.
"This new finding in super aged brains is very exciting," said Changiz Geula, principal investigator of the study and a research professor of neurology at the Cognitive Neurology and Alzheimer's Disease Center at Northwestern's Feinberg School. "It was always assumed that the accumulation of these tangles is a progressive phenomenon through the aging process. But we are seeing that some individuals are immune to tangle formation and that the presence of these tangles seems to influence cognitive performance." Individuals who have few tangles perform at superior levels, while those who have more tangles appear to be normal for their age, Geula noted.
This begs the question: why are some people immune to tangle formation? Do they have immune systems that attack the tangles? Or do they have some genetic variant that lowers oxidative stress in the brain?
Geula will present his findings Sunday, November 16, at the Society for Neuroscience annual meeting in Washington, D.C.
The number of plaques in the brains of the super aged was similar to that in the brains of the normally aging group. The plaque is an aggregation of protein called amyloid that becomes deposited outside the brain cell and disrupts communication between neurons. Like tangles, plaques also are found in modest numbers in the brains of aged individuals and show a dramatic increase in number in Alzheimer's disease.
Geula said the lower number of tangles in the super aged appears to be the critical difference in maintaining memory skills.
Some of the super aged in the study performed memory tasks at the level of people who were about 50 years old. For example, after being told a story, they were able to remember it immediately after and still accurately recall its details 30 minutes later. They also remembered a list of 15 words and recalled these words equally well when tested after 30 minutes.
Stopping brain aging at age 50 wouldn't be ideal. But I'd take it as a good starter. Prevention of tangles won't stop all brain aging though. For example, demyelination (loss of insulation on neurons) would still proceed. We probably need some sort of cell therapy to reverse that process.
Reporting in the online version of the journal Neurobiology of Aging, Dr. George Bartzokis, professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior at UCLA, and his colleagues compared how quickly a group of males ranging in age from 23 to 80 could perform a motor task and then correlated their performances to their brains' myelin integrity. The researchers found a striking correlation between the speed of the task and the integrity of myelination over the range of ages. Put another way, after middle age, we start to lose the battle to repair the myelin in our brain, and our motor and cognitive functions begin a long, slow downhill slide.
The myelination of brain circuits follows an inverted U-shaped trajectory, peaking in middle age. Bartzokis and others have long argued that brain aging may be primarily related to the process of myelin breakdown.
"Studies have shown us that as we age, myelin breakdown and repair is continually occurring over the brain's entire 'neural network,'" said Bartzokis, who is also a member of UCLA's Ahmanson–Lovelace Brain Mapping Center and the UCLA Laboratory of Neuro Imaging. "But in older age, we begin losing the repair battle. That means the average performance of the networks gradually declines with age at an accelerating rate."
As the years go by other things are going wrong in the brain as well. But just preventing demyelination would make a big difference.
Myelin is a phospholipid (fat) insulation layer around the axon sections of neurons. It speeds the transmission of electrical impulses down nerves.
Your finger tapping speed and myelin insulation both peak at about age 39. After that it is all downhill until the development of rejuvenation therapies that will remyelinate the brain.
In the study, each of the 72 participants had a magnetic resonance imaging (MRI) scan that measured the myelin integrity in the vulnerable wiring of their brain's frontal lobes. The maximum finger-tapping speed (the number of taps over a period of 10 seconds) was measured just before the MRI measure was obtained.
The results supported what the researcher had suspected, that finger-tapping speed and myelin integrity measurements were correlated and "had lifespan trajectories that were virtually indistinguishable," according to Bartzokis. And yes, they both peaked at 39 years of age and declined with an accelerating trajectory thereafter.
Bartzokis said these observations are consistent with the hypothesis that "maximum motor speeds depend upon high frequency AP bursts that, in turn, depend on the myelin integrity of the neural networks involved in the task."
"Beginning in middle age," he said, "the process of age-related myelin breakdown slowly erodes myelin's ability to support the very highest frequency AP bursts. That may well be why, besides achy joints and arthritis, even the fittest athletes retire and all older people move slower than they did when they were younger."
So what might a rejuvenating myelin repair therapy look like? In the brain we might need youthful oligodendrocyte glial cells that can replace old glial cells that can no longer do as much myelination. In the peripheral nervous system we'll need rejuvenated Schwann cells that serve a similar function.
Another approach might involve development of drugs or gene therapies that will regulate existing glial cells to turn on their myelination activity. Scientists are studying the genetic regulatory mechanisms of how myelination is controlled with research into genes like LINGO-1, connexin29 and connexin32, WAVE1, and the Quaking gene Qk1 among many others. The many scientists trying to figure out myelin formation and glial cell differentiation are doing valuable work that will help at least some of us avoid the cognitive decay characteristic of aging.
Several myelin-related degenerative disorders such as multiple sclerosis and leukodystrophy provide most of the impetus behind myelin research. In fact, myelination problems might underlie some childhood development disorders and addictive disorders. At this point the idea of manipulating glial cells to reverse general brain aging still seems too unorthodox in the mainstream. But fortunately the need to cure diseases that strike at younger ages provides a compelling rationale for developing therapies which will also help to reverse aging. However, if the desirability and attainability of the goal to reverse aging could become mainstream the amount of resources going into brain rejuvenation therapies would soar and we'd get useful treatments sooner.
Using 1,839 subjects in the Framingham Offspring Study examined with functional magnetic resonance imagining (fMRI) researchers find that even lower levels of alcohol drinking are associated with more rapid brain shrinkage with age.
Increasing alcohol intake was associated with loss in total brain volume greater than expected from age alone (P<0.001), reported Carol Ann Paul, of Wellesley College, and colleagues in the October issue of the Archives of Neurology.
In the cross-sectional study, women were affected more strongly than men by moderate alcohol intake averaging one to two drinks a day (eight to 14 per week).
Do you drink two drinks a day? If so, you are probably getting dumber faster than you need to.
The hope was that cardiovascular benefits of moderate alcohol consumption would keep the brain better fed with blood and slow brain aging. But that hope seems unrealistic now.
The cardiovascular benefits of low to moderate alcohol intake are thought to result from increasing blood flow rates, which would have been expected to benefit the brain also, Paul said.
But rather than preventing normal age-related volume reductions, the effects of moderate drinking were closer to those of heavy drinking, which has been linked to brain atrophy and cognitive decline, the researchers noted.
"Decline in brain volume -- estimated at 2 percent per decade -- is a natural part of aging," says Carol Ann Paul, who conducted the study when she was at the Boston University School of Public Health. She had hoped to find that alcohol might protect against such brain shrinkage.
"However, we did not find the protective effect," says Paul, who is now an instructor in the neuroscience program at Wellesley College. "In fact, any level of alcohol consumption resulted in a decline in brain volume."
Brain rejuvenation is going to be the hardest challenge in rejuvenation. Don't make it any worse by shrinking your brain any faster than unavoidable.
On the bright side, all the hours I spend every day searching for content for blog posts might be stimulating and exercising my brain. Web searching seems to stimulate the frontal, temporal and cingulate areas of your brain. So is all that web surfing really just a prudent anti-aging therapy? Does brain exercise slow brain aging?
For the study, the UCLA team worked with 24 neurologically normal research volunteers between the ages of 55 and 76. Half of the study participants had experience searching the Internet, while the other half had no experience. Age, educational level and gender were similar between the two groups.
Study participants performed Web searches and book-reading tasks while undergoing functional magnetic resonance imaging (fMRI) scans, which recorded the subtle brain-circuitry changes experienced during these activities. This type of scan tracks the intensity of cell responses in the brain by measuring the level of cerebral blood flow during cognitive tasks.
All study participants showed significant brain activity during the book-reading task, demonstrating use of the regions controlling language, reading, memory and visual abilities, which are located in the temporal, parietal, occipital and other areas of the brain.
Internet searches revealed a major difference between the two groups. While all participants demonstrated the same brain activity that was seen during the book-reading task, the Web-savvy group also registered activity in the frontal, temporal and cingulate areas of the brain, which control decision-making and complex reasoning.
"Our most striking finding was that Internet searching appears to engage a greater extent of neural circuitry that is not activated during reading — but only in those with prior Internet experience," said Small, who is also the director of UCLA's Memory and Aging Research Center.
In fact, researchers found that during Web searching, volunteers with prior experience registered a twofold increase in brain activation when compared with those with little Internet experience. The tiniest measurable unit of brain activity registered by the fMRI is called a voxel. Scientists discovered that during Internet searching, those with prior experience sparked 21,782 voxels, compared with only 8,646 voxels for those with less experience.
A paper published in the US Proceedings of the National Academy of Sciences finds that reduced dopamine metabolism in the brain suggests that as we age we experience a reduced capacity to feel rewarded.
Here, by using 6-[18F]FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging.
This seems like a big loss to me. We need stem cell therapies, gene therapies, and nanobot therapies that can go into our brains and repair the accumulated damage and restore youthful function.
Another in my continuing series on why we should develop rejuvenation therapies that will cure aging. Before you die of old age you will spend about the last 15 years of your life getting dumber.
ST. PAUL, Minn. – A new study shows that older people's mental skills start declining years before death, even if they don't have dementia. The study is published in the August 27, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology.
"These changes are different and separate from the changes in thinking skills that occur as people get older," said study author Valgeir Thorvaldsson, MSc, of Göteberg University in Sweden. "We found accelerated changes in people's mental skills that indicated a terminal decline phase years before death."
Your ability to compare figures will go before your spatial ability which in turn will go before your verbal ability. But it is all down, down, down until your whole body crashes.
The start of the decline is different for various cognitive abilities. Perceptual speed, which measures how quickly people can compare figures, begins declining nearly 15 years before death. Spatial ability starts declining nearly eight years before death. And verbal ability starts declining about six-and-a-half years before death.
The study involved 288 people with no dementia who were followed from age 70 to death, with an average age at death of 84. The participants' mental skills were measured up to 12 times over a period of 30 years, and they were evaluated to make sure they had not developed dementia.
A number of factors may explain this terminal decline in mental skills, Thorvaldsson said. "Cardiovascular conditions such as heart disease or dementia that is too early to be detected could be factors," he said. "Increased health problems and frailty in old age often lead to inactivity, and this lack of exercise and mental stimulation could accelerate mental decline."
Thorvaldsson noted that verbal abilities declined sharply in the terminal phase and did not decline significantly due to age only. "This indicates that people remain stable in their verbal abilities unless they are experiencing disease processes that also increase their mortality risk," he said. "A change in verbal ability might therefore be considered a critical marker for degeneration in health in older people."
I do not want to become dumber. Aging is a thief. It steals parts of your mind.
Halting and reversing brain aging is pretty much the most difficult rejuvenation therapy challenge in the human body. For other organs we will be able to grow younger replacements. Got a bad part? Replace it with a newer part. Medicine will become more like auto repair. But the brain needs to be rejuvenated in place. So will will need to focus on stem cells, gene therapy and nanodevices to repair the brain cells in place. That's a much tougher challenge than figuring out how to grow a new liver or kidney.
Here's yet another example of why the aging process should be stopped and reversed by advances in biotechnology. Memory replay by the hippocampus for memory consolidation while sleeping is impaired in old rats.
Aging impairs the consolidation of memories during sleep, a process important in converting new memories into long-term ones, according to new animal research in the July 30 issue of The Journal of Neuroscience. The findings shed light on normal memory mechanisms and how they are disrupted by aging.
During sleep, the hippocampus, a brain region important in learning and memory, repeatedly "replays" brain activity from recent awake experiences. This replay process is believed to be important for memory consolidation. In the new study, Carol Barnes, PhD, and colleagues at the University of Arizona found reduced replay activity during sleep in old compared to young rats, and rats with the least replay activity performed the worst in tests of spatial memory.
Barnes and colleagues recorded hippocampal activity in 11 young and 11 old rats as they navigated several mazes for food rewards. Later, when the animals were asleep, the researchers recorded their hippocampal activity again. In the young animals, the sequence of neural activity recorded while the animals navigated the mazes was repeated when they slept. However, in most of the old animals, the sequence of neural activity recorded during sleep did not reflect the sequence of brain activity recorded in the maze.
"These findings suggest that some of the memory impairment experienced during aging could involve a reduction in the automatic process of experience replay," said Michael Hasselmo, DPhil, at Boston University, an expert unaffiliated with the study.
Animals with more faithful sleep replay also performed better on memory tests. The researchers tested the same 22 rats on a spatial learning and memory task. Consistent with previous research, the young rats recalled the solution to the spatial task faster and more accurately than the old rats. In the old group, the researchers found that the top performers in the spatial memory task were also the ones that showed the best sleep replay. Irrespective of the animal's age, the researchers found that animals who more faithfully replayed the sequence of neural activity recorded in the maze while asleep also performed better on the spatial memory task.
Brain rejuvenation could reverse this trend of diminished ability to form memories as we age. Some day treatments for brain rejuvenation will become available. We would benefit from making that day come sooner.
A new neurology book, “Progress in Brain Research”, provides evidence that the greater tendency to distraction in older brains might bring creative benefits (though most creative work is done while young).
“It may be that distractibility is not, in fact, a bad thing,” said Shelley H. Carson, a psychology researcher at Harvard whose work was cited in the book. “It may increase the amount of information available to the conscious mind.”
I think distractibility involves trade-offs. Makes you better at some things such as dealing with a lot of people in a very interweaved way. But a whole lot of work requires single minded concentration to go through all the steps required. A lot of software development work requires ability to go through large stretches of concentration to build up logical models in your mind. Getting distracted sets you back.
For example, in studies where subjects are asked to read passages that are interrupted with unexpected words or phrases, adults 60 and older work much more slowly than college students. Although the students plow through the texts at a consistent speed regardless of what the out-of-place words mean, older people slow down even more when the words are related to the topic at hand. That indicates that they are not just stumbling over the extra information, but are taking it in and processing it.
When both groups were later asked questions for which the out-of-place words might be answers, the older adults responded much better than the students.
Dr. Carson argues her research shows that students who are less able to filter out unwanted sources of stimuli score as more creative. But are they ultimately more productive? In other words, does this enhanced creativity pay off for them? Do they make more scientific discoveries or technological breakthroughs? Do they succeed more often in creating great advertising campaigns?
We can find plenty of examples of people accomplishing great achievements through hyper-focusing their talents on how to solve a single problem while ignoring distractions from their environment. I suspect we have a surplus of distractible people and a shortage of people who can ignore distractions. Maybe we could make better use of distractible people by putting them in workplaces where they'll encounter fewer distractions. Then maybe their creativity and the need to concentrate can find a better synergy.
Distractibility reminds me of Low Latent Inhibition. Possibly there are different kinds of distractibility and some kinds are more productive than others.
Here's yet another reminder that aging isn't just about creaky bones, gray hair, and wrinkled skin. Brain damage caused by lots of small strokes might account for a third of all old age dementia. Dementia isn't dignified and it doesn't make you wise.
Alzheimer's disease may be what most people fear as they grow older, but autopsy data from a long-range study of 3,400 men and women in the Seattle region found that the brains of a third of those who had become demented before death showed evidence of small vessel damage: the type of small, cumulative injury that can come from hypertension or diabetes.
Dr. Thomas Montine, University of Washington, presented the study results at Experimental Biology 2008 in San Diego on April 6. His presentation was part of the scientific program of the American Society for Biochemistry and Molecular Biology (ASBMB).
In the autopsied brains of people who had experienced cognitive decline and dementia, 45 percent of the risk for dementia was associated with pathologic changes of Alzheimer's disease. Another 10 percent of dementia risk was associated with Lewy bodies, neocortical structural changes that indicate a degenerative brain disease known as Lewy Body Dementia, believed by some clinicians to be a variant of Alzheimer's and/or Parkinson's disease. But a third of the risk for dementia (33 percent) was associated with damage to the brain from small vessel disease.
Dr. Montine and his colleagues believe that, and are now studying in more detail, this small vessel damage is the cumulative effect of multiple small strokes caused by hypertension and diabetes, strokes so small that the person experiences no sensation or problems until the cumulative effect reaches a tipping point. This may be good news, says Dr. Montine. At a time when prevention and treatment for Alzheimer's remain investigational, methods for preventing complications of hypertension and diabetes are currently available.
My guess is that the estimate of a third of all dementia as caused by blood vessel problems might be an underestimate. Other brain aging diseases might develop in part due to poor circulation reducing nutrition to brain cells.
On the bright side, stem cell therapies that repair blood vessels will some day slow brain aging by avoiding accumulation of stroke damage. Better blood vessels will keep the brain better fed and undamaged by blood vessel ruptures.
Here's yet another blog post where I present yet another example of why the people who say that aging is dignified are totally wrong.
New research shows cerebral microbleeds, which are lesions in the brain, are more common in people over 60 than previously thought. The study is published in the April 1, 2008, issue of Neurology®, the medical journal of the American Academy of Neurology.
“We found a three-to-four-fold higher overall prevalence of cerebral microbleeds compared to other studies,” according to study author Monique M.B. Breteler, MD, PhD, with the Erasmus MC University Medical Center in Rotterdam, the Netherlands. “These findings are of major importance since cerebral microbleeds likely reflect cerebrovascular pathology and may be associated with an increased risk of cerebrovascular problems.”
Cerebral microbleeds are lesions that can be seen on brain scans, such as an MRI brain scan. The lesions are deposits of iron from red blood cells that have presumably leaked out of small brain vessels.
For the study, 1,062 healthy men and women who were an average age of 70 underwent an MRI to scan for the presence of cerebral microbleeds. Of the participants, 250 were found to have cerebral microbleeds.
The study found overall prevalence of cerebral microbleeds was high and increased with age from 18 percent in people age 60 to 69 to 38 percent in people over age 80. People with the e4 allele of the APOE gene, which is known to increase the risk of Alzheimer’s disease and of cerebral amyloid angiopathy, had significantly more microbleeds than people without this genetic variant.
We should find ways to repair and halt the damage of aging. Rejuvenating stem cell therapies could repair our blood vessels and prevent cerebral microbleeds. We could avoid the resulting brain damage and keep more of who we are intact.
Update: Read all about Strategies for Engineered Negligible Senescence to get an idea of how we can hope to some day stop and reverse aging of the brain and of other parts of our bodies.
Boston, MA—Researchers from Boston University School of Medicine (BUSM) have estimated that one in six women are at risk for developing Alzheimer’s disease (AD) in their lifetime, while the risk for men is one in ten. These findings were released today by the Alzheimer’s Association in their publication 2008 Alzheimer’s Disease: Facts and Figures.
The higher incidence of Alzheimer's among women comes as a result of women living longer. Basically, the longer you live the higher the odds you'll get Alzheimer's (and other degenerative diseases of the brain) and die from it.
Stroke and dementia are the most widely feared age-related neurological diseases, and are also the only neurological disorders listed in the ten leading causes of disease burden.
The researchers followed 2,794 participants of the Framingham Heart Study for 29 years who were without dementia. They found 400 cases of dementia of all types and 292 cases of AD. They estimated the lifetime risk of any dementia at more than one in five for women, and one in seven for men.
Our brains are aging. This is bad. When we get into our 70s and 80s our brains will really start to malfunction. Did I mention this is bad? Can you still remember two sentences later that I mentioned this is bad? Isn't it really handy that you can remember a sentence long enough to see logical connections between sentences? Don't you want to continue to be able to do this? This is an argument for a very aggressive program to develop brain rejuvenation therapies using stem cells and gene therapies. Yes, we should develop rejuvenation therapies as an urgent priority. In the mean time fish oils DHA and EPA appear to slow down brain aging and reduce the risk of Alzheimer's. So lets slow down our brain aging while we try to develop the means to reverse brain aging.
• As many as 5.2 million people in the United States are living with Alzheimer’s.
• 10 million baby boomers will develop Alzheimer's in their lifetime.
• Every 71 seconds, someone develops Alzheimer’s.
• Alzheimer's is the seventh-leading cause of death.
• The direct and indirect costs of Alzheimer's and other dementias to Medicare, Medicaid and businesses amount to more than $148 billion each year.
Those costs do not include the costs of lower earnings since we can't think as productively as our minds become messed up and less able to function.
A new study of 856 people age 71 years and older found that 22 percent had some cognitive impairment that did not reach the threshold for dementia (Article, p. 427). Each year, about 8 percent of individuals with cognitive impairment but not dementia at baseline died and about 12 percent progressed to dementia. Using the 22 percent figure, researchers calculate that in 2002 in the United States, 5.4 million people aged 71 and older had cognitive impairment without dementia. Previous estimates of cognitive impairment without dementia ranged from 5 percent to 29 percent.
Bear in mind (at least while you can) that some old folks have Alzheimer's, others have dementia, still others have cognitive impairment that falls short of getting classified as dementia, and still others have impairment due to stroke or Parkinson's Disease.
But on the bright side the incidence of cognitive impairment among the elderly appears to be declining.
ANN ARBOR, Mich. — Although it’s too soon to sound the death knell for the “senior moment,” it appears that memory loss and thinking problems are becoming less common among older Americans.
A new nationally representative study shows a downward trend in the rate of “cognitive impairment” — the umbrella term for everything from significant memory loss to dementia and Alzheimer’s disease — among people aged 70 and older.
The prevalence of cognitive impairment in this age group went down by 3.5 percentage points between 1993 and 2002 — from 12.2 percent to 8.7 percent, representing a difference of hundreds of thousands of people.
Lower rates of smoking probably contributed to this improvement. Cholesterol lowering drugs and better diets might have helped too. Ditto for lower levels of air pollution.
Recent work led by University of Iowa neuroscientist Natalie Denburg, Ph.D., suggests that for a significant number of older adults, measurable neuropsychological deficits do seem to lead to poor decision-making and an increased vulnerability to fraud. The findings also suggest that these individuals may experience disproportionate aging of a brain region critical for decision-making.
"Our research suggests that elders who fall prey to fraudulent advertising are not simply gullible, depressed, lonely or less intelligent. Rather, it is truly more of a medical or neurological problem," said Denburg, who is an assistant professor of neurology in the UI Roy J. and Lucille A. Carver College of Medicine. "Our work sheds new light on this problem and perhaps may lead to a way to identify people at risk of being deceived."
Brain aging is gradual brain damage. Some people think aging is wonderful and natural. That's tantamount to saying that brain damage is wonderful and natural.
The Iowa Gambling Task (IGT) seems like a handy test for large corporations to use to detect when their top executives should retire.
Denburg's most recent study, published Dec. 2007 in the Annals of the New York Academy of Sciences, shows that 35 to 40 percent of a test group of 80 healthy older adults with no apparent neurological deficits have poor decision-making abilities as tested in a laboratory experiment known as the Iowa Gambling Task (IGT). The IGT is a computerized decision-making test where participants draw cards from different decks with the aim of maximizing their winnings. Some of the decks yield good results in aggregate, while others yield poor outcomes.
When you feel your brain slipping stop watching TV advertising, throw out all junk mail, and hang up on all phone callers who are trying to sell you something. You will lose the ability to handle that stuff.
Following the poor decision-makers through several additional tests, the researchers found that in addition to the poor performance on the IGT, this subgroup of older adults also were more likely to fall prey to deceptive advertising.
Using a set of real advertisements that had been deemed misleading by the Federal Trade Commission and several counterpart, non-deceptive advertisements, the study showed that the poor decision-makers are much less able to spot inconsistencies and pick up on deceptive messages than good decision-makers. Poor decision-makers also were more likely to indicate an intention to buy the article advertised in the misleading advertisement. In contrast, there was no difference in comprehension of non-deceptive advertisements between the two groups of older adults.
Imagine a future era when routine brain scans as we age will warn us when our ventromedial prefrontal cortex (VMPC) begins to give out. At that point you'll become easy prey for con artists. Yet another reason why we should support the development of brain rejuvenation therapies as an urgent need.
Another group of patients who perform poorly on the IGT and have abnormal bodily responses to the test are individuals with acquired damage to the ventromedial prefrontal cortex (VMPC) -- an area of the brain that appears to be critical for good decision-making.
"Our hypothesis is that older poor decision-makers have deficits in their prefrontal cortex," Denburg explained. "The next element of our study will be to complete structural and functional brain-imaging studies to see if we can identify differences between poor decision-makers and good decision-makers either in brain structure or in how the brain functions during decision-making tasks."
I hear Mick Jagger singing "What a drag it is getting old." If only we already had rejuvenation therapies he could make another album as great as Exile On Main Street.
Most children are able to imagine their future selves as astronauts, politicians or even superheroes; however, many older adults find it difficult to recollect past events, let alone generate new ones. A new Harvard University study reveals that the ability of older adults to form imaginary scenarios is linked to their ability to recall detailed memories.
Aging is destruction. Aging is loss. We should defeat aging.
According to the study, episodic memory, which represents our personal memories of past experiences, “allows individuals to project themselves both backward and forward in subjective time.”
Therefore, in order to create imagined future events, the individual must be able to remember the details of previously experienced ones extract various details and put them together to create an imaginary event, a process known as the constructive-episodic-simulation.
Harvard psychologists Donna Rose Addis, Alana Wong and Daniel Schacter supported the hypothesis using an adapted version of the Autobiographical Interview in which young and older participants responded to randomly selected cue words with past and future scenarios.
When compared with young adults, the researchers found that the older adults displayed a significant reduction in the use of internal episodic details to describe both past memories and imagined future events.
The results of the study, which appear in the January 2008 issue of Psychological Science, a journal of the Association for Psychological Science, not only reveal that there is a link between age-related memory deficits and future planning in older adults, but raise questions concerning the involvement of other types of memory, as well.
We need effective brain rejuvenation therapies such as cell therapies and gene therapies. Aging is loss. Aging of your brain is progressive loss of parts of your past and parts of your identity. It is even a gradual loss of your imagination.
Out of all the aspects of aging I hate brain aging most of all. My brain is who I am. I do not want to lose the intellectual abilities I currently possess. In fact, I want more brain power, not less. Well, a group of researchers at Harvard, Washington University of St. Louis, and University of Michigan have found that as we age different parts of the brain become less in sync with each other.
The researchers assessed brain function in a sample of adults ranging in age from 18 to 93 and comprising 38 young adults and 55 older adults. They did so using functional magnetic resonance imaging (fMRI), which uses harmless radio waves and magnetic fields to measure blood flow in brain regions, which in turn reflects activity.
To assess the integrity of functional connections between brain areas, the researchers used fMRI to measure spontaneous low-frequency fluctuations known to reflect the activity of such connections. The researchers concentrated on large-scale connections between frontal and posterior brain regions that are associated with high-level cognitive functions such as learning and remembering.
The researchers reported a “dramatic reduction” in functional connections when they compared the younger and older groups.
I do not want to undergo a “dramatic reduction” in my brain's functional connections. If anyone doubts the desirability of development of rejuvenation therapies ask yourself whether you want to gradually lose parts of your brain and to become less able to think as you age. What aging costs you is far more than a less pretty appearance or a reduction in athletic ability. You aren't just gaining more aches and pains. You are losing parts of your mind.
The researchers also used an MRI technique called “diffusion tensor imaging” to measure the integrity of white matter in the brains of the subjects. This technique reveals details of the structure of brain tissue. Their analysis revealed that the reduced functional connection they detected in brain areas of the older subjects was correlated with decreased white matter integrity.
When the researchers tested the subjects’ cognitive function, they found that “Those individuals exhibiting the lowest functional correlation also exhibited the poorest cognitive test scores.”
The cognitive test score results tend to validate the use of the MRI techniques to measure brain conditions. Granted measured levels of brain activity are open to interpretation. But note that they didn't just measure brain activity. They measured quantity of white matter and connections.
Among the older individuals, some of the subjects’ brains systems were correlated, and older individuals that performed better on psychometric tests were more likely to have brain systems that were in sync. These psychometric tests, administered in addition to the fMRI scanning, measured memory ability, processing speed and executive function.
Among older individuals whose brain systems did not correlate, all of the systems were not affected in the same way. Different systems process different kinds of information, including the attention system, used to pay attention, and the default system, used when the mind is wandering. The default system was most severely disrupted with age. Some systems do remain intact; for example, the visual system was very well preserved. The study also showed that the white matter of the brain, which connects the different regions of the brain, begins to lose integrity with age.
My guess is the decay in white matter is the cause of the decay in linkage between the parts of the brain.
The researchers used PET scans to measure amyloid plaque build-up in order to screen out people who were developing Alzheimer's Disease. They wanted to see how aging changes brains of people who are not developing Alzheimer's. So these results apply to us as we age even if we don't developer Alzheimer's.
They focused on the links within two critical networks, one responsible for processing information from the outside world and one, known as the default network, which is more internal and kicks in when we muse to ourselves. For example, the default network is presumed to depend on two regions of the brain linked by long-range white matter pathways. The new study revealed a dramatic difference in these regions between young and old subjects. “We found that in young adults, the front of the brain was pretty well in sync with the back of the brain,” said Andrews-Hanna. “In older adults this was not the case. The regions became out of sync and they were less correlated with each other.” Interestingly, the older adults with normal, high correlations performed better on cognitive tests.
We need rejuvenation therapies. But first we need a society-wide awareness and acceptance of potential and need to develop rejuvenation therapies. Our minds are at stake.
A new study published in the New England Journal of Medicine finds many of us unknowingly have abnormalities such as mini-strokes in our brains.
Methods The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated postprocessing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained.
Results Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence.
An aneurysm is a bulge in the wall of a blood vessel. A brain infarct is a stroke where blood got cut off to some part of the brain. Basically, a lot of people are walking around with small strokes in their brains without knowing it. Others have circulatory problems that might eventually cause damage.
Regarding benign tumors: Harvard Medical School researcher Judah Folkman, the pioneer in the use of anti-angiogenesis drugs (which block blood vessel growth) to stop cancer, includes slides in his lectures of cross sections of organs of adult humans stained to show tumors. Well, we have lots of little tumors which are stuck at small size because the tumors haven't yet mutated to secrete lots of angiogenesis compounds. So the tumors can't grow the blood vessels needed to fuel their growth and they get stuck at small sizes. Well, that's what these benign brain tumors probably are.
What this report illustrates is how much our brains decay as we get older. If you feel at peace with your aging keep in mind that you are losing brain cells and some of the remaining brain cells that aren't dying are at least becoming senescent or damaged.
Stem cell and gene therapies to rejuvenate our blood vessels will some day prevent and reverse the brain circulatory system decay. The sooner these therapies come the less of your brain you'll have to lose while waiting. So support accelerated development of rejuvenation therapies.
Cholesterol lowering statin drug simvastatin appears to cut the risk of degenerative neurological disorders Alzheimer's Disease and Parkinson's Disease by nearly half.
Boston, MA -- Researchers from Boston University School of Medicine (BUSM) have found that the statin, simvastatin, reduces the incidence of Alzheimer’s disease and Parkinson’s disease by almost 50 percent. This is the first study to suggest that statins might reduce the incidence of Parkinson’s disease. These findings, will be published in the July online open access journal BioMed Central (BMC) Medicine.
Alzheimer’s disease or dementia is one of the major public health threats that individuals face as they age. Statins are a class of medications that reduce cholesterol by inhibiting HMG-CoA reductase.
The researchers examined data from the Decision Support System database of the United States Veterans Affairs Medical System, a database of medical centers throughout the United States which contains diagnostic, pharmaceutical and demographic information on approximately 4.5 millions people.
Using three different models for analysis, the researchers examined the effects of three different statins (atorvastatin, lovastatin and simvastatin) and found that simvastatin showed a strong reduction in the incidence of Alzheimer’s disease in each of the models. The data also showed the same statin was associated with a reduced incidence of Parkinson’s disease.
The researchers speculate that the selective benefit observed with simvastatin might be due to the combination of high potency and the ability to enter the brain.
Might the disease risk reduction come as a side effect of lowering cholesterol? That mechanism of action would tend to slow the accumulation of plaque in arteries in the brain. But the other statins did not yield as big a benefit. This suggests that even those of us with low cholesterol might derive benefit from taking simvastatin.
If you are taking Zocor, Lipex, or a generic equivalent then you are taking simvastatin. Mevacor and Altocor are simvastatin brand names. Also, Lipitor and Torvast are atorvastatin brand names. My guess is that they didn't study Crestor because it is relatively newer and without as many long term users.
An international team led by Benjamin Wolozin, MD, at Boston University School of Medicine used data from the US Veterans Affairs Database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The researchers used statistical models to compare different statins, looking at data on over 700,000 simvastatin users and more than 50,000 atorvastatin users. The team targeted those aged 65 or over with no prior diagnosis of Alzheimer’s disease, who had been taking statins for at least seven months.
The researchers found that for subjects aged 65 and over, simvastatin was linked with a significantly reduced number of cases of dementia and Parkinson's disease". The researchers also made the surprising finding that not all statins are equal when it comes to dementia or Parkinson’s disease. A small reduction in dementia cases was seen among those who regularly take atorvastatin, which did not reach a level of statistical significance. Lovastatin was not found to have any significant effect on dementia, and neither atorvastatin nor lovastatin were associated with a reduction in the number of cases of Parkinson’s disease.
Statins might reduce Alzheimer's and Parkinson's risks by anti-inflammatory effects. Statins might change the rate of cellular beta amyloid synthesis or secretion. Though the evidence is not clear.
Since brain aging is the hardest part of aging to reverse any treatments that slow down the rate of brain aging and degeneration have great value. We need to keep our brains alive while waiting for the gene therapies, cell therapies, and nanodevice therapies that will allow us to turn back the biological clock on brain aging processes.
Some oppose the development of therapies to reverse aging because they argue that aging is a beautiful and dignified natural process. In this Panglossian view of aging the silver in one's hair is akin to a measure of accumulated wealth of wisdom and understanding. But the reality is a much uglier accumulation of losses - most notably including cognitive losses. For example, older people experience a declining ability to comprehend humor.
July 11, 2007 -- It's no laughing matter that older adults have a tougher time understanding basic jokes than do younger adults.
It's partially due to a cognitive decline associated with age, according to Washington University in St. Louis researchers Wingyun Mak, a graduate student in psychology in Arts & Sciences, and Brian Carpenter, Ph.D., Washington University associate professor of psychology.
Humor comprehension in older adults functions in a different fashion than humor comprehension in younger adults. The researchers studied older adults from a university subject pool as well as undergraduate students. The subjects participated in tests that indicated their ability to complete jokes accurately as well as tests that indicated their cognitive capabilities in areas of abstract reasoning, short-term memory, and cognitive flexibility. Overall, older adults demonstrated lower performance on both tests of cognitive ability as well as tests of humor comprehension than did younger adults.
Aging is an accumulation of damage and losses. We should defeat aging. The breakdown and decay of our metabolisms is a bad thing. We need rejuvenation therapies. Such therapies are on the horizon but we should push harder to pull that prospect closer in our future.
Few older people die with brains untouched by a pathological process, however, an individual’s likelihood of having clinical signs of dementia increases with the number of different disease processes present in the brain, according to a new study. The research was funded by the National Institute on Aging (NIA), part of the National Institutes of Health, and conducted at the Rush Alzheimer’s Disease Center at Rush University Medical Center in Chicago. Julie Schneider, M.D., and colleagues report the findings in the journal Neurology online today.
Among their findings is the observation that the combination of Alzheimer’s disease and cerebral infarcts (strokes) is the most common mix of pathologies in the brains of people with dementia.
A diet to improve your blood lipid profile will help delay the day when strokes and other aging processes start you down the road to serious brain damage.
The implication of these findings is that public health efforts to prevent and treat vascular disease could potentially reduce the occurrence of dementia, the researchers say in the paper.
What would reduce the incidence of dementia: All the dietary, lifestyle, and drug factors that reduce the risk of stroke and heart disease. In this context I hear Ray Davies singing "I'm an ape man" since the Ape Diet of U Toronto researcher David Jenkins looks like a good bet for how to reduce the incidence of cardiovascular diseases.
The bad news is that most people have multiple serious brain diseases by the time they die.
The current study compared clinical and autopsy data on the first 141 participants who have died.
Annual physical and psychological exams showed that, while they were alive, 50 of the 141 had dementia. Upon death, a neuropathologist, who was unaware of the results of the clinical evaluation, analyzed each person’s brain. The autopsies showed that about 85 percent of the individuals had evidence of at least one chronic disease process, such as Alzheimer’s disease, strokes, Parkinson’s disease, hemorrhages, tumors, traumatic brain injury or others.
Comparison of the clinical and autopsy results showed that only 30 percent of people with signs of dementia had Alzheimer’s disease alone. By contrast, 42 percent of the people with dementia had Alzheimer’s disease with infarcts and 16 percent had Alzheimer’s disease with Parkinson’s disease (including two people with all three conditions). Infarcts alone caused another 12 percent of the cases. Also, 80 of the 141 volunteers who died had sufficient Alzheimer’s disease pathology in their brains to fulfill accepted neuropathologic criteria for Alzheimer’s disease, although in life only 47 were clinically diagnosed with probable or possible Alzheimer’s disease.
Growing oldn't isn't just about getting gray and wrinkled skin. Growing old is not graceful or dignified. Your brain becomes progressively more damaged.
Stem cell therapies, gene therapies, and other future therapies will eventually slow brain aging and in the longer run rejuvenation therapies together will reverse brain aging. We should demand greater efforts to develop all those brain rejuvenation therapies because currently we are all mentally decaying. Every day that goes by our brains get older and more dysfunctional.
ST. PAUL, MN- People who are easily distressed and have more negative emotions are more likely to develop memory problems than more easygoing people, according to a study published in the June 12, 2007, issue of Neurology®, the scientific journal of the American Academy of Neurology.
In the study, those who most often experience negative emotions such as depression and anxiety were 40 percent more likely to develop mild cognitive impairment than those who were least prone to negative emotions. Mild cognitive impairment is a transitional stage between normal aging and dementia. People with mild cognitive impairment have mild memory or cognitive problems, but have no significant disability.
Researchers analyzed the results from two larger studies, the Religious Orders Study and the Memory and Aging Project, which involved 1,256 people with no cognitive impairment. During up to 12 years of follow-up, 482 people developed mild cognitive impairment. Participants were evaluated on their level of proneness to distress and negative emotions by rating their level of agreement with statements such as “I am not a worrier,” “I often feel tense and jittery,” and “I often get angry at the way people treat me.”
Some people are probably innate worriers. So maybe the insight that negative emotions age your brain is hard to act upon. Still, you can try to make life choices that are less likely to put you in positions where you have to worry. For example, avoid lots of debt. Also, don't get hooked up with a romantic attachment that will stress you out. Sometimes you know what is coming and you do it anyway (and I'm speaking from personal experience). Don't do that. Also, stressful job? Start looking for another one.
CHICAGO --- Northwestern University researchers have discovered a drug that slows – and may even halt – the progression of Parkinson’s disease. The drug rejuvenates aging dopamine cells, whose death in the brain causes the symptoms of this devastating and widespread disease.
D. James Surmeier, the Nathan Smith Davis Professor and chair of physiology at Northwestern University’s Feinberg School of Medicine, and his team of researchers have found that isradipine, a drug widely used for hypertension and stroke, restores stressed-out dopamine neurons to their vigorous younger selves. The study is described in a feature article in the international journal Nature, which will be published on-line June 10.
What would isradipine do for aging minds in general? We all have dopamine neurons. Those neurons age in all of us, albeit at a slower rate than they age in people who have Parkinson's.
Decades of research have not produced a single drug that slows the rate of neuronal cell death in Parkinson's.
“There has not been a major advance in the pharmacological management of Parkinson’s disease for 30 years,” Surmeier said.
Thousands of drugs exist in pharmacies. Why did it take decades before someone tried isradipine? Surmeier made a basic discovery about the behavior of adult dopaminergic neurons: unlike most neurons they use calcium for signaling rather than sodium.
First, Surmeier observed that dopamine neurons are non-stop workers called pacemakers. They generate regular electrical signals seven days a week, 24 hours a day, just like pacemaker cells in the heart. This was already known. But then he probed more deeply and discovered something very strange about these dopamine neurons.
Most pacemaking neurons use sodium ions (like those found in table salt) to produce electrical signals. But Surmeier found that adult dopamine neurons use calcium instead.
Actually, other types of neurons use calcium as well though in a more limited manner. My knowledge on this is rather dated at this point but calcium fluxes across membranes help initiate waves of depolarization at the dendrite end of neurons when neurotransmitters bind to a dendrite's receptors. But apparently dopamine neurons use calcium more extensively and instead of sodium.
Aged dopamine neurons switch to using calcium instead of sodium (why?) and this calcium has toxic effects on dopamine neurons that probably makes them wear out more rapidly.
When the neurons are young, Surmeier found they actually use sodium ions to do their work. But as the neurons age, they become more and more dependent on the troublesome calcium and stop using sodium. This calcium dependence – and the stress it causes the neurons --is what makes them more vulnerable to death.
So then would long term use of isradipine slow general brain aging?
Surmeier decided to block off calcium channels in dopamine cells by use of isradipine. The result: the dopamine cells switched over to use of less toxic sodium instead.
What would happen, Surmeier wondered, if he simply blocked the calcium’s route into the adult neuron cells" Would the neurons revert to their youthful behavior and start using sodium again"
“The cells had put away their old childhood tools in the closet. The question was if we stopped them from behaving like adults would they go into the closet and get them out again"” Surmeier asked. “Sure enough, they did.”
When he gave the mice isradipine, it blocked the calcium from entering the dopamine neuron. At first, the dopamine neurons became silent. But within a few hours, they had reverted to their childhood ways, once again using sodium to get their work done.
“This lowers the cells’ stress level and makes them much more resistant to any other insult that’s going to come along down the road. They start acting like they’re youngsters again,” Surmeier said.
Hat's off to this scientist and his team. Good job.
WASHINGTON— Researchers at the Johns Hopkins and Yale university medical schools have found that a simple blood test to measure uric acid, a measure of kidney function, might reveal a risk factor for cognitive problems in old age. Of 96 community-dwelling adults aged 60 to 92 years, those with uric-acid levels at the high end of the normal range had the lowest scores on tests of mental processing speed, verbal memory and working memory.
The findings appear in the January issue of Neuropsychology, which is published by the American Psychological Association (APA).
High-normal uric acid levels, defined in this study as 5.8 to 7.6 mg/dL for men and 4.8 to 7.1 mg/dL for women, were more likely to be associated with cognitive problems even when the researchers controlled for age, sex, weight, race, education, diabetes, hypertension, smoking and alcohol abuse. These findings suggest that older people with serum (blood) uric-acid levels in the high end of the normal range are more likely to process information slowly and experience failures of verbal and working memory, as measured by the Wechsler Adult Intelligence Scale and other well-established neuropsychological tests.
“It might be useful for primary-care physicians to ask elderly adults with high normal serum uric acid about any problems they might be having with their thinking, and perhaps refer those who express concern, or whose family members express concern, for neuropsychological screening,” says lead author David Schretlen, PhD.
The link between high-normal uric acid and cognitive problems is also sufficiently intriguing for the authors to propose clinical studies of whether medicines that reduce uric acid, such as allopurinol, can help older people with high-normal uric acid avoid developing the mild cognitive deficits that often precede dementia.
Would the growth of younger replacement kidneys prevent the rise of uric acid with age? Or could stem cell therapies or gene therapies do the trick?
For reasons that are not entirely clear, uric acid levels increase with age, says Dr. Schretlen. Higher levels of uric acid are linked with known risk factors for dementia, including high blood pressure, atherosclerosis, Type 2 diabetes and the “metabolic syndrome” of abdominal obesity and insulin resistance. Dr. Schretlen also says there is mounting evidence that end-stage renal (kidney) disease increases the risk of cognitive dysfunction and dementia in elderly adults. Given this web of connections, uric acid could potentially become a valuable biological marker for very early cognitive problems in old age.
If our uric acid levels are rising as a side effect of kidney aging and if the higher uric acid levels deliver no real benefit then efforts to keep uric acid down would slow brain aging. The brain is the toughest rejuvenation challenge. Anything we can to do delay brain aging will give us more time to find ways to make 100 billion neurons in our brains young again.
Update: As some commenters have pointed out, this study does not prove the direction of causation runs from higher uric acid to faster brain aging. Another possible direction of causality runs from high oxidative stress to both higher uric acid and faster brain aging. The higher oxidative stress could impair kidney function and brain function and cause higher uric acid to correlate with faster brain aging. Or the body could make more uric acid as a protectant against certain kinds of radicals. For example, uric acid appears to protect against peroxynitrite. So the higher uric acid might be an indicator of some other problem that is causing the accelerated brain aging.
Early diabetes suppresses uric acid. Yet diabetes increases oxidative stress and accelerates aging. Could it be that effects of diabetes are worsened by the lower uric acid? Also, insulin prevents oxidative stress-caused decreases in intracellular uric acid and in intracellular antioxidant glutathione. Perhaps rather than take drugs to lower uric acid a person with high uric acid should first try a variety of antioxidants and other brain protecting compounds.
Update II: Bonnie Firestein's research team at Rutgers University have found that uric acid stimulates brain astroglial cells to make transporter proteins that haul away compounds that do damage to nerves and uric acid may therefore be neuroprotective.
Uric acid's effects on the health of neurons had been observed by other researchers, but the mechanics of how it confers protection has remained a mystery.
"It is interesting to note that people with gout never seem to develop multiple sclerosis," Firestein said. "In animal models of multiple sclerosis, the addition of uric acid reduces symptoms and improves prognosis. The same is true for one type of Parkinson's disease tested."
The Firestein team's breakthrough studies revealed that uric acid can stimulate astroglial cells to produce transporter proteins that carry harmful compounds away from neurons in jeopardy of chemical damage. This opens the door to identifying a unique drug target for new therapies.
Glutamate is a compound that under normal circumstances aids neurons in transmitting signals for cognitive functions in the brain, such as learning and memory. In the case of spinal cord injury or stroke where there is physical cell damage, however, an excess of glutamate is released and it accumulates around the remaining intact neurons, eventually choking them to death.
When Firestein's group added uric acid to a mixed culture of rat spinal cord neurons and astroglial cells, the production of the glutamate transporter EAAT-1 increased markedly. The challenge now is find the most effective strategy for increasing the production of the transporter, using drug therapies or other means.
So then does the higher blood uric acid increase brain aging or decrease it?
The brain is going to be the hardest organ in the body to rejuvenate. But prevention of damage is more important than repair because loss of brain cells means loss of information. Replacement of brain cells won't give you back lost memories. One way we can prevent brain cell loss is to prevent blockages in small arteries in the brain.
A team of UC San Diego physicists and neuroscientists has discovered a bottleneck in the network of blood vessels in the brain that makes it vulnerable to strokes. The finding may explain the origin of the puzzling damage to the brain’s gray matter often detected in brain scans, especially among the elderly.
In the study, published this week in the journal Proceedings of the National Academy of Sciences, the researchers used a laser technique they developed to precisely monitor changes in blood flow resulting from an induced blockage in a tiny artery, or arteriole, in the brains of anesthetized rats. They found that the penetrating arterioles, which connect the blood vessels on the brain’s surface with deeper blood vessels, are a vulnerable link in the network.
“The blood vessels on the surface of the brain are like a collection of city streets that provide multiple paths to get somewhere,” explained David Kleinfeld, a professor of physics at UCSD, who led the team. “If one of the vessels is blocked, blood flow quickly rearranges itself. On the other hand, the penetrating arterioles are more like freeways. When blocked, the blood flow is stopped or slowed significantly in a large region round the clot.”
Many more people have had strokes than are aware of it. So lots of old people suffer from reduced cognitive ability and loss of memory due to silent strokes.
The obstruction of blood flow resulted in damage to the surrounding brain area, which the researchers report resembled damage seen in the brains of humans and thought to be the result of “silent strokes.” Silent strokes have attracted attention recently because magnetic resonance imaging has made it possible to follow changes in the brains of individuals as they age. MRI scans have revealed that, over time, small holes accumulate in the gray matter of many patients, including those who have no obvious behavioral signs of a stroke.
I do not want to get lots of holes in my brain gray matter as the years go by.
The researchers say their results support the hypothesis, made by clinicians, that the penetrating arterioles may be the location of small strokes that cause the death of sections of brain tissue in humans. The accumulation of damage may lead to memory loss, and may be a risk factor for having a larger stroke, according to Pat Lyden, a professor of neurosciences at UCSD’s School of Medicine and head of the UCSD Stroke Center.
Development of youthful artery stem cells that can replace aged stem cells could help repair brain arteries and by doing so avoid silent strokes that wipe out pockets of neurons in the brain. Genetic engineering of the liver to improve blood cholesterol could also reduce the risk of brain damage from stroke and poor circulation.
We need faster progress on stem cell research. The survival of our brain cells is at stake.
The common assumption had been that the brain drain was due to a decreasing supply of neural stem cells in the aging hippocampus, said lead study investigator Bharathi Hattiangady, Ph.D., research associate in neurosurgery. Neural stem cells are immature cells that have the ability to give rise to all types of nerve cells in the brain.
In the current study, however, the researchers found that the stem cells in aging brains are not reduced in number, but instead they divide less frequently, resulting in dramatic reductions in the addition of new neurons in the hippocampus.
To conduct their census, the researchers attached easy-to-spot fluorescent tags to the neuronal stem cells in the hippocampus in young, middle-aged and old rats.
Parenthetically, the hippocampal stem cells are not the only stem cells in brains. But the hippocampal stem cells are important because of the hippocampus's role in formation of new memories.
The rat hippocampus has only 50,000 stem cells and the number does not diminish with age.
They found that in young rats, the hippocampus contained 50,000 stem cells -- and, significantly, this number did not diminish with aging. This finding, the researchers said, suggested that the decreased production of new neurons in the aged brain was not due to a lack of starting material.
The researchers then used another fluorescent molecule to tag all stem cells that were undergoing division in the process of staying "fresh" in case they were recruited to become mature nerve cells.
While the number of hippocampal stem cells does not change the percentage engaged in cell division (during which new neurons are formed) does diminish with age.
They found that in young rats, approximately 25 percent of the neural stem cells were actively dividing, but only 8 percent of the cells in middle-aged rats and 4 percent in old rats were dividing. This decreased division of stem cells is what causes the decreased neurogenesis, or birth of nerve cells, seen with aging, the scientists said.
The reported difference in the percentage of neural stem cells dividing may even understate the difference in the rate of generation of new neurons. If the old stem cells divide more slowly then the difference in the rate generation of new stem cells may be even greater than the multiple of 6.25 (25 divided by 4) we might expect as the difference in rate of new neuron generation.
Replacement of aged stem cells by younger stem cells will some day be a core component of rejuvenation therapies. So how many neural stem cells will we need to replace in our hippocampuses? Some human brains weigh 1400 grams as compared to 2 grams for a rat.. The difference is approximately a factor of 700 (though human and rat brain sizes vary considerably). So if we could create 700 times 50,000 or about 35 million human neural stem cells and inject them into a human brain's hippocampus we should be able to make our aging brains act younger again.
Think about that. We know one of the causes of lower brain performance as we age: A very small portion of all brain cells gradually lose their ability to divide. That portion of brain aging is a problem that seems solvable within a couple of decades at most.
A human brain contains about 100 billion neurons. All the neurons age. We need to find ways to rejuvenate all those 100 billion neurons. That's probably the toughest challenge in human rejuvenation because we have to fix all those cells rather than replace them. But the very small fraction of that 100 billion that are the hippocampal neural stem cells play an outsize role and they are are obvious candidates for replacement.
Now, one issue arises: Suppose we can find a way to deliver new neural stem cells. How to get rid of the old stem cells ones that are already there? Likely the neural stem cells have a mechanism for regulating their total number. So delivery of new younger stem cells might cause some of the older ones to commit cellular suicide (known as apoptosis). But it might be necessary to do several rounds of replacement stem cell therapy to gradually weed out the older stem cells.
What I want to know: If we had a way to create young hippocampal stem cells could needles deliver the cells safely into the hippocampus without causing brain damage in the process? Or could surgeons guide a flexible tube up arteries to the hippocampus to deliver the stem cells that way? Or how else could the stem cells get delivered?
What else I'd like to know: Do people who have better memories have more neural stem cells in their hippocampuses? Or do their neural stem cells get triggered more easily to divide? The potential exists to use replacement neural stem cell therapy as a way to bring in stem cells that are genetically engineered to form memories more rapidly.
Rochester, Minn. -- Researchers from Mayo Clinic have discovered that allergic rhinitis is associated with the development of Parkinson's disease later in life. Findings will be published in the Aug. 8 issue of the journal Neurology.
"The association with Parkinson's disease is increased to almost three times that of someone who does not have allergic rhinitis," says James Bower, M.D., Mayo Clinic neurologist and lead study investigator. "That's actually a pretty high elevation."
Previous studies had shown that people who regularly take nonsteroidal anti-inflammatory drugs, such as ibuprofen, are less likely to develop Parkinson's disease. These results prompted the Mayo Clinic investigators to look further into the links between diseases characterized by inflammation and Parkinson's. They studied 196 people who developed Parkinson's disease, matched with people of similar age and gender who did not develop Parkinson's. The study was conducted in Olmsted County, Minn., home of Mayo Clinic, over a 20-year period.
The researchers examined these groups to determine if those who developed Parkinson's disease had more inflammatory diseases. They found that those with allergic rhinitis were 2.9 times more likely to develop Parkinson's. They did not find a similar association between inflammatory diseases such as lupus, rheumatoid arthritis, pernicious anemia or vitiligo and Parkinson's disease. The researchers hypothesize that they may not have found significant links between these diseases and Parkinson's disease due to the relatively small number of those in the population who have these diseases, and thus the small number with these diseases in their population sample study. They also did not find the same association with Parkinson's disease in patients with asthma that they discovered in those with allergic rhinitis.
Would fairly regular use of Flonase (nasal anti-allergy spray) reduce the risk of Parkinson's? Or would antihistamines reduce the risk?
Researchers from the Erasmus Medical Center in the Netherlands studied around 5,300 participants over the age of 55, and found that those who had the highest intake of vitamin B6 had up to a 50 percent reduction in Parkinson's disease risk.
The researchers suspect that B6 exerts a protective effect by lowering blood homocysteine. If that is the mechanism then other nutrients that lower homocysteine (most notably folic acid) might also reduce the risk of Parkinson's.
New Haven, Conn.--One of two separate areas of the brain light up when younger people look at a house or a face, but each image activates both areas of the brain at the same time in older persons, according to a study published by Yale University and the University of Illinois, Urbana-Champaign, this month in NeuroReport.
Although the researchers cannot say for sure, one theory that needs further study is that the extra activity in older adults is probably compensation for age-related changes in brain volume or efficiency, according to Christy Marshuetz, assistant professor in the Department of Psychology and a co-author of the study.
The study included a dozen people 18- to 27-years-old, and an equal number of 61- to 80-year-olds. They were asked to remember three images of houses or three images of faces and then asked to decide if another image was from the original set. Functional magnetic resonance imaging was used to track neural changes during these tasks.
I hate brain aging the most out of all aging. Brain aging is going to be the hardest problem to solve because we will be able to grow replacements for most organs. But the brain has your identity and memory. It needs to be repaired and rejuvenated by fixing all of its cells.
Our brains try to compensate for getting old.
They hypothesized that even when consciously remembering specific items, older adults would show decreased specialization in the fusiform face area of the brain and the parahippocampal place area of the brain when compared with younger adults. The researchers also expected, and found, more activity in older adults in the frontal cortex and believe this activity is compensation for less differentiation in the visual cortex at the back of the brain.
We need treatments that will repair old brain cells. Gene therapies will some day bring in replacement DNA to fix mitochondria that no longer work well and gene therapies will also bring in enzymes that will cut up junk that accumulates in cells.
The arrival of brain rejuvenation therapies will cause an economic boom when smart old minds become younger and energetic once again. Combine rejuvenation with therapies that increase intelligence and memory and the economic boom will get even larger still.
Researchers at the University of Edinburgh have identified for the first time a certain area of the brain which can shrink in old age and cause depression and Alzheimer's disease. The scientists believe the shrinkage may be caused by high levels of stress hormones.
They examined the size of a special region of the brain, the anterior cingulate cortex, that might be involved in controlling stress hormones. In a significant discovery, scientists found that people with a smaller anterior cingulate cortex had higher levels of stress hormones.
Doctors analysed stress hormone levels and brain volume in two groups of ten healthy male volunteers aged 65-70 for the study. Lead author Dr Alasdair MacLullich said: "Doctors have known for several years that ageing, and certain diseases common in ageing like Alzheimer's disease and depression, can be associated with shrinkage of the brain, but this is the first time we have been able to show that increased levels of stress hormones may cause shrinkage of this critical area of the brain.
"This is an important new finding because the anterior cingulate cortex shows damage in ageing, depression, and Alzheimer's disease, and stress hormones are often high in these conditions. The discovery deepens doctors' understand of ageing, depression and Alzheimer's diseases, and will help in the development of treatments based on reducing high levels of stress hormones."
The abstract for this research indicates they were looking at cortisol as the stress hormone.
Of course there's the possibility that the cortisol is a consequence of the shrunken anterior cingulate cortex or they are both a consequence of a third factor and that other factor is causing the brain shrinkage without cortisol in the chain of causes and effects. But my guess is the cortisol is causing accelerated brain aging.
If you want to live longer avoid a lifestyle and occupation that causes you to experience chronic stress. Anyone know of good research on environmental factors that relieve or cause stress?
Researchers at the UCSD School of Medicine working with scientists at Elan Pharmaceuticals, have reported promising results in mice of a vaccine approach to treating Parkinson’s and similar diseases. These results appear in the June edition of the journal Neuron.
Dr. Eliezer Masliah, Professor of Neurosciences and Pathology at UCSD, and colleagues at UCSD and Elan Pharmaceuticals in San Francisco, vaccinated mice using a combination of the protein that abnormally accumulates in the brains of Parkinson’s (called human alpha-synuclein) and an adjuvant. This approach resulted in the generation of anti-alpha synuclein antibodies in mice that are specially bred by Masliah’s team to simulate Parkinson’s disease, resulting in reduced build-up of abnormal alpha-synuclein. The accumulation of abnormal alpha-synuclein is associated with degeneration of nerve cells and interference with normal inter-cellular communication, leading to Parkinson’s disease and dementia.
The work marks the first time a vaccine for this family of diseases has been found effective in animal studies. Scientists at Elan Pharmaceuticals have been working for the past few years in a vaccine for Alzheimer’s Disease.
The researchers focused on a spectrum of neurological disorders called Lewy body disease, which include Parkinson’s and Alzheimer’s. These disorders are marked by the presence of Lewy bodies -- abnormal clumps of alpha-synuclein -- in the brain. Normally, alpha-synuclein proteins support communications between brain cells, or neurons. However, when abnormal proteins clump together in the neurons, a build-up of synuclein can cut off neuron activity, blocking normal signaling between brain cells and ultimately choking the cells to death.
“We found that the antibodies produced by the vaccinated mice recognized and reduced only the abnormal form of alpha-synuclein, since the protein’s normal form is in a cellular compartment where antibodies can’t reach it,” said Masliah. “Abnormal alpha-synuclein finds its way to the cell membrane, where antibodies can recognize it.”
A few years ago a vaccine trial against beta amyloid plaques which accumulate in Alzheimer's Disease reduced plaque build-up in many of the study participants. But in a few percent of the patients the vaccine caused an immune response which led to inflammation of the brain. This led to a halt of that vaccine development effort due to an expectation that regulators would not approve such a treatment. Well, if I was diagnosed with Alzheimer's I'd be willing to run a 3% or 4% risk of brain inflammation if my alternative was the gradual destruction of my brain. But the FDA is impervious to that sort of reasoning.
A similar fear of brain inflammation with a Parkinson's vaccine means these researchers are looking for some other way to deliver what is essentially an immunotherapy. While not mentioned here the obvious alternative choice is monoclonal antibodies. The advantage of monoclonal antibodies is that they get broken down by the body. So unlike a vaccine they might not cause a permanent change in the immune system. On first signs of an inflammation response the treatment could be stopped. Also, a vaccine probably causes the immune system to make a number of different antibody types and only one of those types might contribute to the inflammation. A monoclonal antibody approach would allow a much narrower and controllable set of antibodies to be made and delivered.
Masliah stressed that the team’s experimental active immunization, while effective in mice, may not be as useful in humans. “We would not want to actively immunize humans in this way by triggering antibody development, because one could create harmful inflammation,” he cautioned. “However, it might be feasible to inject antibodies directly, as if the patient were creating his or her own.”
The team, the first to identify the presence of these proteins in the human brain, originally thought the protein played an important role in the development of Alzheimer’s disease. Then, an explosion of research linked Lewy bodies and their constituent proteins to both Alzheimer’s and Parkinson’s. The team spent four years clarifying alpha-synuclein’s role in Parkinson’s, developing a mouse model that contained the faulty and normal genes for alpha-synuclein, and conducting the experiments that led to their current findings.
With evidence that this approach could be effective in treating Lewy Body disease, the UCSD researchers are now working with Elan Pharmaceuticals to develop alternative ways to produce alpha-synuclein antibodies, with the goal of making a vaccine that is safe and effective in humans. While this research could take many years and holds no promise of prevention or cure, the researchers are hopeful that the mouse studies are a step in the right direction.
“This shows the first demonstration of a vaccine for this family of disease,” Masliah said.
Attempts to develop vaccines and monoclonal antibodies against Parkinson's Disease and Alzheimer's Disease fit within the typology of 7 Strategies for Engineered Negligible Senescence (SENS), more specifically the strategy to remove accumulated extracellular junk. It is quite possible that immunotherapies against Alzheimer's and Parkinson's will turn out to provide benefits to people who are not diagnosed with either Parkinson's or Alzheimer's. We might all accumulate some amount of either amyloid plaques or misshapen alpha-synuclein. If that is the case then immunotherapies to remove these build-ups might someday become routine as people grow older.
CHICAGO - Mild cognitive impairment in older people is not a normal part of growing old but rather appears to be an indicator of Alzheimer's disease or cerebral vascular disease, according to a study published in the March 8 issue of the journal, Neurology.
"The study shows that mild cognitive impairment is often the earliest clinical manifestation of one or both of two common age-related neurologic diseases," said Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center and the principal author of the paper. "From a clinical standpoint, even mild loss of cognitive function in older people should not be viewed as normal, but as an indication of a disease process," said Bennett.
This is the first study involving a large number of subjects who were followed until they developed mild cognitive impairment or dementia, and then died. The study involved examining brain tissue from 180 people, including 37 with mild cognitive impairment, 60 without cognitive impairment, and the rest with dementia. All were Catholic nuns, priest or brothers who agreed to participate in the National Institute on Aging (NIA) funded Religious Orders Study. Since 1993 more than 1000 persons have agreed to annual clinical evaluations and to donate their brains to the Rush investigators at the time of death.
Study participants took tests of memory, language, attention and other cognitive abilities each year to document their clinical status. The diagnosis of mild cognitive impairment (MCI) was made when impaired performance on these tests was not severe enough to warrant a diagnosis of dementia. After death, the investigators measured the amount of Alzheimer's disease pathology and cerebral infarcts (strokes) through brain autopsy. Of the 37 individuals with MCI, more than half (23) met pathologic criteria for Alzheimer's disease, and nearly a third (12) had cerebral infarcts (this include five with both). Less than a quarter (9) did not have either pathology.
"Because most people with mild cognitive impairment progress to dementia, it has been difficult to obtain brain tissue from persons who die while they still have the condition," said Bennett. "We now know that both clinically and pathologically, mild cognitive impairment patients are in the middle in terms of the disease process for Alzheimer's disease and cerebral vascular disease," said Bennett.
One positive finding from the study is that one-third (60) of the total study participants with an average age of 85 did not experience cognitive decline over several years of follow-up. Yet, about half of these persons had significant Alzheimer's disease pathology and nearly a quarter had cerebral vascular disease. "It is likely that these individuals have some type of 'reserve' capacity in their brains that allows them to escape the loss of memory despite the accumulation of pathology," said Bennett.
Bennett and his colleagues are involved in another NIA funded study at Rush, the Memory and Aging Project, trying to identify what keeps these individuals from becoming impaired. "Preventing the accumulation of disease pathology is a common approach to disease prevention," said Bennett. "Another way to prevent loss of cognition is to identify factors that protect us from becoming forgetful despite this pathology.
"From a public health perspective, the number of people with cognitive loss due to Alzheimer's disease and cerebral vascular disease is probably much larger than current estimates," said Bennett. He hopes that these data provide additional impetus to research efforts to develop treatments and, ultimately, prevention for these common diseases of aging.
On the downside if you live into your 80s the odds of suffering from cognitive declines are very high. Your odds of living into your 80s are going to rise with future advances in biotechnology and biomedical science. So most of us should see this report as describing the likely future of our brains - barring the development of treatments that prevent these diseases.
Treatments for Alzheimer's Disease and for cerebral vascular disease would benefit much larger numbers of people than current estimates of disease incidence would suggest. Therefore the value of developing treatments for these diseases is even greater that previous estimates would lead one to believe. A great increase in biomedical science funding would pay very rich dividends.
You gotta ask yourself: Do you want your brain to rot? Well, do you?
Hamilton, ON. February 2, 2005 – The long-held belief that older people perform slower and worse than younger people has been proven wrong. In a study published today in Neuron, psychologists from McMaster University discovered that the ageing process actually improves certain abilities: Older people appear to be better and faster at grasping the big picture than their younger counterparts.
"Going into the study, we knew that ageing changes the way people see the world," says Allison Sekuler, one of the senior authors and a Canada Research Chair at McMaster. "But these results are an unusual twist on the standard 'ageing makes you worse' story, and they provide clear insight into what is changing in the ageing brain."
Using computer-generated stimuli, the researchers monitored how much time subjects needed to process information about the direction in which a set of bars moved. When the bars were small, or when the bars were low in contrast (light gray vs. dark gray), younger subjects took less time to see the direction of motion. But when the bars were large, and high in contrast (black vs. white), older subjects outperformed the younger subjects.
"The results are exciting not only because they show an odd case in which older people have better vision than younger people, but also because it may tell us something about how ageing affects the way signals are processed in the brain" says Patrick Bennett, the other senior author, also a Canada Research Chair at McMaster.
The results suggest that as we age, the ability of one brain cell to inhibit another is reduced. That sort of inhibition helps young people find an object hidden among clutter, but it can make it hard to tune into the clutter itself. When the young brain sees big, high-contrast bars, it effectively tunes out because there is no object hidden in the bars. But older brains do not inhibit information in the same way, so they do not tune out the bars, and they can actually perform the task better.
"As we get older, it becomes harder to concentrate on one thing and ignore everything else," says Bennett. "It takes more effort to tune out distractions. We've seen it in cognition and speech studies, and now we see it in vision. Although we don't know if those are all linked, we think the visual effect is due to changes in the effectiveness of inhibitory neurotransmitters in the brain." Neurotransmitters are chemical substances that can modify the way in which brain cells talk to one another. Some neurotransmitters enhance brain signals, and others inhibit them.
Is this change in ability the result of aging or of the accumulation of mental abilities? Is it desireable to be able to reverse this aspect of aging? What would be the consequences of restoring a more youthful reaction to high contrast and low contrast signals?
Harvard researchers have found in the on-going Nurses' Health Study that elderly women who drink one alcoholic beverage a day experience less cognitive decline than otherwise similar women who do not have a daily drink.
"Low levels of alcohol appear to have cognitive benefits," said Francine Grodstein of Brigham and Women's Hospital in Boston, senior author on the study, published in today's New England Journal of Medicine. "Women who consistently were drinking about one-half to one drink per day had both less cognitive impairment as well as less decline in their cognitive function compared to women who didn't drink at all," Grodstein said.
This result is expected to hold for men as well.
They found that the women who had the equivalent of one drink a day had a 23% lower risk of becoming mentally impaired during the two-year period, compared with non-drinkers.
Stampfer and colleagues focused on more than 12,400 Nurses' Health Study participants. The women were 70 to 81 years old. The researchers collected information about the women's alcohol intake as part of a food questionnaire every two to four years, starting in 1980. They asked the women how often on average they drank beer, wine, or liquor during the previous year.
The results held true even after the researchers factored in characteristics about the women that could have confused the findings, such as age, education, how many friends and family members they had, how much exercise they got, and whether they had any other health problems.
The suspected mechanism by which alcohol delivers this benefit is improved blood flow. This suggests a few things. First, younger people who have improved blood flow may not gain any cognitive benefit from drinking alcohol. So it might make more sense to delay making a daily drink as part of your routine until late middle age. Though I'd like to see more research on this point.
Another point is that alcohol is not the only way available - or even the most powerful way - to improve blood flow or for preventing a decline in blood flow. A heart healthy diet and lifestyle is probably the best bet for keeping strong blood flow available in all parts of the body. Foods low in saturated fats, lots of fruits and vegetables and some nuts as well would all be good bets. I'm going to guess that nuts high in arginine will eventually be shown to be especially beneficial on this count. Plus, plenty of exercise, sufficient sleep, avoidance of chronically stressing situations, and of course no smoking are wise lifestyle choices.
Another point here is that statin drugs that keep cholesterol down may also slow the rate of cognitive decline. In the future stem cell therapies that allow the circulatory system to be rejuvenated will also reduce the rate of cognitive decline. Though note that poor circulation is only one cause of cognitive decline. Other causes of brain aging must also be addressed before cognitive decline can be halted and even reversed.
CHICAGO --- Chronic back pain, a condition afflicting many Americans, shrinks the brain by as much as 11 percent — equivalent to the amount of gray matter lost in 10 to 20 years of normal aging, a Northwestern University research study found.
Loss in brain density is related to pain duration, indicating that 1.3 cubic centimeters of gray matter (the part of the brain that processes information and memory) are lost for every year of chronic pain, said lead researcher A. Vania Apkarian, associate professor of physiology at Northwestern University Feinberg School of Medicine and a researcher at the Northwestern University Institute of Neuroscience.
The study, the first to examine brain changes in chronic pain conditions, was published in the Nov. 23 issue of The Journal of Neuroscience.
About 6 percent of the American population is probably suffering from brain shrinkage from chronic back pain. On top of that there are people suffering from chronic stomach pain and other forms of chronic pain. So it is likely that more than 20 million Americans are suffering cognitive losses due to chronic pain.
At least 25 percent of Americans suffer from back pain; in one fourth of these individuals, back pain is chronic and unremitting.
Although chronic pain greatly diminishes quality of life and increases anxiety and depression, it previously had been assumed that the brain reverts to its normal state after chronic pain stops.
Apkarian and co-researchers used structural magnetic resonance imaging brain scan data and two automated analysis techniques to contrast brain images from 26 participants with chronic back pain with those from matched normal subjects.
All participants with chronic back pain had unrelenting pain for more than a year, primarily localized to the lumbosacral region, including buttocks and thighs, with or without pain radiating to the leg.
The participants were divided into neuropathic — exhibiting pain because of sciatic nerve damage — and non-neuropathic. Brain scans showing gray matter volume were compared.
In earlier research, Apkarian and colleagues found that back pain sustained for six months or longer is accompanied by abnormal brain chemistry, indicated by chemical changes in the area of the brain known to be important in making emotional assessments, including decision-making and for controlling social behavior. Based on these results, Apkarian’s laboratory group embarked on the brain atrophy study.
It is possible that some of the observed decreased gray matter shown in this study reflects tissue shrinkage without substantial neuronal loss, suggesting that proper treatment would reverse this portion of the decreased brain gray matter, Apkarian said.
The atrophy also may be attributable to more irreversible processes, such as neurodegeneration. Other research has shown that spinal cord neurons undergo apoptosis — cell death — in rats with neuropathic pain.
“Given that, by definition, chronic pain is a state of continuous persistent perception with associated negative affect and stress, one mechanistic explanation for the decreased gray matter is overuse atrophy caused by excitotoxic and inflammatory mechanisms,” Apkarian said.
The researchers hypothesize that atrophy of brain circuitry involved in pain perception may dictate the properties of the pain state, such that as atrophy of elements of the circuitry progresses, the pain condition becomes more irreversible and less responsive to therapy.
Other researchers on the study were Yamaya Sosa, physiology; Sreepadma Sonty, neurology; Robert M. Levy, M.D., neurosurgery; R. Norman Harden, M.D., physical medicine and rehabilitation; Todd B. Parrish, radiology; and Darren R. Gitelman, M.D., neurology, radiology and the Cognitive Neurology and Alzheimer’s Disease Center, at Feinberg.
St. Paul, Minn. – Women who are obese throughout life are more likely to lose brain tissue, according to a study published in the November 23 issue of Neurology, the scientific journal of the American Academy of Neurology. Loss of brain tissue has been linked to cognitive decline.
Researchers in Sweden studied the relationship between body mass index and brain atrophy (loss of brain tissue) in 290 women. The women were born between 1908 and 1922 and had four follow-up examinations between 1968 and 1992. During the final exam, they had a computed tomography (CT) scan to measure for any loss of brain tissue. Body mass index (BMI) is a measure of body fat that shows weight adjusted for height. Overweight is a BMI of 25 to 30 kg/m2. Obesity is a BMI of 30 kg/m2 and above.
An overweight or obese BMI was linked to a loss of tissue specifically in the temporal lobe. Nearly 50 percent (144) of the women had temporal atrophy. At the time of CT scan, their body mass index was an average of 27 kg/m2, which was 1.1 to 1.5 kg/m2 higher than the women without brain atrophy. Overall the women’s BMI increased over the 24-year period, but the increase was greater for those who lost tissue in the temporal lobe. The risk of atrophy increased 13 to 16 percent per 1.0 kg/m2 increase in BMI.
“This study indicates that a high BMI is a risk factor for dementia in women. Other studies have reported similar findings,” said Deborah Gustafson, PhD, of Sahlgrenska University Hospital in Göteborg, Sweden and also the Medical College of Wisconsin in Milwaukee. “Obesity is another factor that should be actively intervened upon to reduce diseases of advanced aging.”
The researchers didn’t pinpoint a reason why obesity leads to brain atrophy. They said there are several possible mechanisms.
“Obesity is related to ischemia, hypertension, and cerebrovascular and cardiovascular diseases. These conditions contribute to an unhealthy vascular system, and therefore, to a higher dementia risk,” said Gustafson. “Obesity may also increase the secretion of cortisol, which could lead to atrophy.”
The temporal lobe appears to be highly susceptible to the effects of ischemia and other vascular diseases in the brain, and is evidence of cerebral degeneration and neuronal death, Gustafson said.
These two reports effectively raise the stakes for two major health problems. Losses in cognitive ability have huge macroeconomic and personal costs. Overweight people with chronic pain suffer a cognitive double whammy. We need both better treatments for chronic pain and better therapies to prevent obesity.
UCLA neuroscientists using a new MRI analysis technique to examine myelin sheaths that insulate the brain's wiring report that as people age, neural connections that develop last degenerate first. The computer-based analysis method is unique in its ability to examine specific brain structures in living people at millimeter resolution.
Published online by the Neurobiology of Aging earlier this year and scheduled to appear in the August 2004 print edition of the peer-reviewed journal, the study offers new insights into the role of myelin in brain aging and its contribution to the onset of Alzheimer's disease. In addition, the success of the MRI analysis technique opens new opportunities for studying the impact of lifestyle on brain aging and for developing medications that could slow aging or prevent Alzheimer's disease.
"The study increases our understanding of the role of myelin in brain development and degeneration, and demonstrates the usefulness of this MRI method for examining the single most powerful risk for Alzheimer's disease by far — age," said Dr. George Bartzokis, the study's lead investigator and visiting professor of neurology at the David Geffen School of Medicine at UCLA. He also is director of the UCLA Memory Disorders and Alzheimer's Disease Clinic and clinical core director of the UCLA Alzheimer's Disease Research Center.
Myelin is a sheet of lipid, or fat, with very high cholesterol content — the highest of any brain tissue. The high cholesterol content allows myelin to wrap tightly around axons, speeding messages through the brain by insulating these neural "wire" connections.
As the brain continues to develop in adulthood and as myelin is produced in greater and greater quantities, cholesterol levels in the brain grow and eventually promote the production of a toxic protein that together with other toxins attacks the brain. This toxic environment disrupts brain connections and eventually also leads to the brain/mind-destroying plaques and tangles visible years later in the cortex of Alzheimer's patients.
"The brain is not a computer, it is much more like the Internet," Bartzokis said. "The speed, quality and bandwidth of the connections determine its ability to process information, and all these depend in large part on the insulation that coats the brain's connecting wires.
"The results of our study show that in older age, the myelin insulation breaks down, resulting in a decline in the speed and efficiency of our Internet. Myelin and the cells that produce it are the most vulnerable component of our brain — the human brain's Achilles' heel," he said. "This safe, non-invasive technology can assess the development and degeneration of the brain's insulation in specific regions. Now that we can measure how brain aging proceeds in vulnerable regions, we can measure what treatments will slow aging down and thus begin in earnest to look at preventing Alzheimer's disease."
The UCLA research team examined the deterioration of myelin in the brain's splenium and genu regions of the corpus callosum, which connects the two sides of the brain. Neural connections important to vision develop early in life in the splenium, while connections important to decision‑making, memory, impulse control and other higher functions develop later in the genu.
The team found that the brain connections deteriorated three times as fast in the genu compared to the splenium. The study also notes that myelin deterioration is far greater throughout the brain of patients with Alzheimer's disease than in healthy older adults. The late myelinating regions are much more vulnerable and may be why the highest levels of reasoning and new memories are the first to go when one develops Alzheimer's disease, while movement and vision are unaffected until very late in the disease process.
We need a way to reseed the brain with the cells that make myelin. We also need ways to remove the accumulated toxic compounds that accumulate in the intercellular spaces as well as the toxic compounds (and junk that simply takes up increasing space) that accumulate inside cells. These are 3 of the 7 basic Strategies for Engineered Negligible Senescence (SENS) which you ought to read all about if you haven't already.
This result comes on the heels of another recent study that found brains older than 40 show lots of signs of damaged genes and expression of more repair and inflammation enzymes.
Update: Note how once again a new technique that enables the measurement of phenomena which were not previously measurable has enabled new discoveries to be made. While this initial discovery is interesting the technique itself will be more important in the long run because it will enable many more future discoveries. Better scientific tools are more important than any particular discoveries made with the tools.
To investigate age-associated molecular changes in the human brain, Dr. Bruce A. Yankner, professor in the Department of Neurology and Division of Neuroscience at Children's Hospital Boston and Harvard Medical School, and colleagues examined patterns of gene expression in postmortem samples collected from thirty individuals ranging in age from 26 to 106 years. Using a sophisticated screening technique called transcriptional profiling that evaluates thousands of genes at a time, the researchers identified two groups of genes with significantly altered expression levels in the brains of older individuals. A gene's expression level is an indicator of whether or not the gene is functioning properly.
"We found that genes that play a role in learning and memory were among those most significantly reduced in the aging human cortex," said Yankner. "These include genes that are required for communication between neurons."
In addition to a reduction in genes important for cognitive function, there was an elevated expression of genes that are associated with stress and repair mechanisms and genes linked to inflammation and immune responses. This is evidence that pathological events may be occurring in the aging brain, possibly related to gene damage.
The researchers then went on to show that many of the genes with altered expression in the brain were badly damaged and could not function properly. They showed that these genes also could be selectively damaged in brain cells grown in the laboratory, thereby mimicking some of the changes of the aging brain.
"Our findings suggest that these genes are unusually vulnerable to damage from agents such as free radicals and toxins in the environment," said Yankner. "The brain's ability to cope with these toxic insults and repair these genes declines with age, leading to their reduced expression. It will now be important to learn how to prevent this damage, and to understand precisely how it impacts brain function in the elderly."
According to Yankner, "If you examine brain gene patterns among young adults, they are quite similar. In very old adults, there is some increased variability, but there is still similarity between individuals. In contrast, individuals in the middle age population between 40 and 70 years of age are much more variable. Some middle-aged individuals exhibit gene patterns that look more like the young group, whereas others show gene patterns that look more like the old group."
This is evidence that people may age differently during middle age. It will now be of great interest to understand what it is that makes some people age more rapidly than others.
These findings raise the exciting possibility that treatments or lifestyles that reduce gene damage in young adults may delay cognitive decline and the onset of brain diseases in later years. However, more research is needed.
"We can repair these aging genes in the laboratory, but that is a far cry from the human brain. This is only a first step," cautions Yankner.
The brain is going to be the hardest organ to repair and rejuvenate. With most organs we are going to be able to just grow replacements or at least replace pieces. But each of your neurons involved in memory or personality encode a part of who you are. Killing off old neurons kills off some small part of who you are. We need to be able to repair individual aged cells. That is going to be hard to do.
The hardest problem is going to be the development of gene therapy techniques for delivering genes into brain cells. The removal of extracellular accumlated junk is probably a more solvable problem as vaccines have already showed considerable promise in removing the beta amyloid plaques involved in Alzheimer's Disease. It is possible that the removal of at least some of the intracellular junk may not turn out to require gene therapy. But my guess is that part of the intracellular junk that accumulates in lysosomes will require gene therapies developed to provide enzymes that can break down that junk.
We need much greater funding and effort aimed at developing brain rejuvenation therapies. We also need a lot more research aimed at discovering why some brains age more rapidly than others. However, it is very likely that just improving blood lipid and cholesterol profiles will reduce the oxidative load on the brain and therefore reduce the rate of brain aging. The sorts of dietary and exercise advice aimed at avoiding heart disease and cancer will very likely slow brain aging as well.
If this report of middle aged signs of brain aging makes the problem more real to you and makes you feel you ought to do something to protect your brain then consider the "ape" diet to improve blood lipids and cholesterol. The ape diet uses a combination of nuts, foods high in soluble fiber (e.g. eggplant), margarines fortified with plant sterols, soy, and vegetables. The ape diet lowers cholesterol, C Reactive Protein (an inflammation indicator), and triglycerides.
There is now a large accumulation of studies which show that cholesterol-lowering statin drugs reduce the risk of Alzheimer's Disease and vascular dementia. Though be aware that some statin drug users experience acute memory problems. Still, you can always stop taking a statin drug or switch to a different one if you experience harmful cognitive effects. But if you are not going to take statins then for the sake of your brain at least consider being like an ape man when you eat and lower your cholesterol that way. Ray Davies had it all figured out years ago when he sang "I'm an ape man, I'm an ape ape man, oh I'm an ape man. I'm a King Kong man, I'm a voodoo man, oh I'm an ape man".
Also see my previous posts Brain Aging Studied With Gene Microarrays, Myelin Cholesterol and Iron Build-Up Leads To Alzheimer's, GABA Neurotransmitter Rejuvenated Aged Monkey Brains, Vitamin C, E In High Dose Combination May Protect Against Alzheimer's.