Partial Recall: Why Memory Fades with Age

Partial Recall: Why Memory Fades with Age

Study finds that the disruption of white matter conduits in the aging brain keeps its regions from communicating effectively

 

 
WHAT WAS THAT AGAIN?: A study led by a group at Harvard determined that degradation of white matter pathways that connect different brain regions may be behind fading memory associated with aging.

As we age, it becomes harder and harder to recall names, dates—even where we put down our keys. Although we may fear the onset of Alzheimer's, chances are, our recollective powers have dulled simply because we're getting older—and our brains, like our bodies, are no longer in tip-top shape.

But what is it that actually causes memory and other cognitive abilities to go soft with senescence? Previous research has shown that bundles of axons (tubular projections sent out by neurons to signal other nerve cells) wither over time. These conduits, collectively referred to as white matter, help connect different regions of the brain to allow for proper information processing.

Now, researchers have found that these white matter pathways erode as we age, impairing communication or "cross talk'' between different brain areas.

"What we were looking at was the communication or cross talk between different regions of the brain," says study co-author Jessica Andrews-Hanna, a Harvard University graduate student. "The degree to which white matter regions are actually stable predicts the degree to which other regions are able to communicate with each other."

Andrews-Hanna and other Harvard researchers (along with collaborators at the University of Michigan at Ann Arbor and Washington University in St. Louis) concluded that white matter naturally degrades as we age—causing disrupted communication between brain regions and memory deficits—after conducting a battery of cognitive tests and brain scans on 93 healthy volunteers, ages 18 to 93. Participants fell into two age groups: one 18 to 34 and the other 60 to 93 years of age.

Scientists asked study subjects to perform several cognitive and memory exercises, such as determining whether certain words referred to living or nonliving objects. As they answered, researchers monitored activity in the fronts and backs of their brains with functional imaging magnetic resonance imaging (fMRI) to determine whether those areas were operating in sync. The results, published in Neuron: communication between brain regions appeared to have "dramatically declined" in the older group.

They fingered the potential reason for the dip by doing further brain scans using diffusion tensor imaging, an MRI technique that gauges how well white matter is functioning by monitoring water movement along the axonal bundles. If communication is strong, water flows as if cascading down a celery stalk, says Randy Buckner, a cognitive neuroscientist at Harvard; if it is disrupted, the pattern looks more like a drop of dye in a water bucket that has scattered in all directions. The latter was more evident in the older group, an indication that their white matter had lost some of its integrity.

The older crowd's performance on memory and cognitive skill tests correlated with white matter loss: The seniors did poorly relative to their younger peers. The researchers note that the white matter appears to fray more over time in the forebrain than in the brain's rear. They speculate that age-related depletion of neurotransmitters (the chemical signals sent between neurons) as well as the shrinking of gray matter (the tissue made up of the actual nerve cell bodies and supporting cells) also contribute to dimming memory and cognitive skills.

Buckner says that the team now plans to examine how aging affects white matter as well as gray matter and neurotransmitters. "We want to know," he says, "is this an important factor in why some people age gracefully and others age less gracefully?"

Best Treatment Option for Mental Disorders May Come Down to Genes

Best Treatment Option for Mental Disorders May Come Down to Genes

A dopamine-receptor gene variation is linked to changes in brain function, possibly neurotransmitter signaling 

 
THE DRUGS DON'T WORK: Variations in the gene that codes for the D2 receptor protein could influence the way certain antipsychotics work in the brains of mentally ill patients.

Alterations in the genetic coding for a nerve cell receptor, which detects a chemical signal that is key to behavioral change, could point the way to designing therapies most effective for patients suffering from schizophrenia, drug addiction and other mental illnesses.

"I don't know if what we just published is a viable biomarker," says Wolfgang Sadee, chair of the Department of Pharmacology at The Ohio State University (O.S.U.) College of Medicine and the co-author of a report on the finding published this week in Proceedings of the National Academy of Sciences USA. "But, I think there's a good chance that this is a biomarker that we will at least test and we will know soon if there is something worthwhile."

A team of scientists from O.S.U. examined 68 samples of postmortem tissue from the brains of people without a history of mental illness in search of the profile of messenger RNA (mRNA) transcribed from a particular gene. (mRNA is the intermediate blueprint between gene and protein.) Researchers were specifically hunting for the mRNA created from the two alleles (copies) of the gene DRD2, which codes for a receptor protein for the neurotransmitter dopamine. D2 dopamine receptor malfunction has been linked to drug addiction, schizophrenia and Parkinson's disease. The team focused its search on the striatum (a midbrain region implicated in planning and movement) and the prefrontal cortex, the brain's central processing area.

In 15 of the brain samples, researchers found that one copy of DRD2 was producing at least 50 percent more mRNA than the other one; in the remaining brains, they discovered that both alleles produced equal amounts. They also identified SNPs (single nucleotide polymorphisms, or alterations to the genetic code created by the addition or deletion of a single nucleotide in a gene's long chain). Two of these changes caused differences in the protein made by the gene; one of them appeared to be the result of DRD2 gene being spliced together differently, resulting in a protein consisting of a slightly longer than normal chain of amino acid building blocks.

The unexpected finding of a splice variant caused some excitement in the lab, Sadee says, because, according to the literature "the short form is more inhibitory and the long form may be facilitating dopaminergic transition. … When dopaminergic input comes in, [individuals with the SNPs on one gene copy] would have a chance of having more transmission" than those with two normal copies of the gene.

Sadee contacted Alessandro Bertolino at the University of Bari in Italy, who was doing research that involved monitoring the brain activity of 117 volunteers with functional magnetic resonance imaging (fMRI) during memory tests. Seventeen of the subjects in Bertolino's pool carried the SNPs on a single allele and showed increased activity in their striata and prefrontal cortices during the mental exercises, yet performed worse on the memory tests and had less attention control than the other study participants.

Sadee speculates that the brains of these subjects may be in "unnecessary hyperdrive. The dopamine stimulates more activity and that relates to more brain activity during a memory task," he says. "That is maybe not as good as memory function. … The brain has to work harder to master the same task, and that's induced by this polymorphism."

He says the study could improve current treatments for patients suffering from mental illnesses. The proper antipsychotic drugs may in the future be determined by genotyping patients to assure the most positive effect. Physicians now often have to try out different drugs to test their effectiveness, because this class of medications is highly varied and targets different brain receptors. Such findings as these could dramatically reduce the guesswork involved, thereby leading to the proper prescription from day one. Currently, Sadee says, antipsychotics are only effective 50 to 60 percent of the time and take five to six weeks to begin working. 

"The influence of antipsychotics that inhibit D2 antagonist activity will differ between the two" forms of the protein receptor, he says. "One is facilitating and the other inhibiting, so the net effect of inhibiting the D2 receptor will change. So, we think that is one possible mechanism for differences in antipsychotic response." 

Coal Ash Is More Radioactive than Nuclear Waste

Coal Ash Is More Radioactive than Nuclear Waste

By burning away all the pesky carbon and other impurities, coal power plants produce heaps of radiation

 

 
CONCENTRATED RADIATION: By burning coal into ash, power plants concentrate the trace amounts of radioactive elements within the black rock.

The popular conception of nuclear power is straight out of The Simpsons: Springfield abounds with signs of radioactivity, from the strange glow surrounding Mr. Burn's nuclear power plant workers to Homer's low sperm count. Then there's the local superhero, Radioactive Man, who fires beams of "nuclear heat" from his eyes. Nuclear power, many people think, is inseparable from a volatile, invariably lime-green, mutant-making radioactivity.

Coal, meanwhile, is believed responsible for a host of more quotidian problems, such as mining accidents, acid rain and greenhouse gas emissions. But it isn't supposed to spawn three-eyed fish like Blinky.

Over the past few decades, however, a series of studies has called these stereotypes into question. Among the surprising conclusions: the waste produced by coal plants is actually more radioactive than that generated by their nuclear counterparts. In fact, fly ash—a by-product from burning coal for power—contains up to 100 times more radiation than nuclear waste.

At issue is coal's content of uranium and thorium, both radioactive elements. They occur in such trace amounts in natural, or "whole," coal that they aren't a problem. But when coal is burned into fly ash, uranium and thorium are concentrated at up to 10 times their original levels.

Fly ash uranium sometimes leaches into the soil and water surrounding a coal plant, affecting cropland and, in turn, food. People living within a "stack shadow"—the area within a half- to one-mile (0.8- to 1.6-kilometer) radius of a coal plant's smokestacks—might then ingest small amounts of radiation. Fly ash is also disposed of in landfills and abandoned mines and quarries, posing a potential risk to people living around those areas.

In a 1978 paper for Science, J. P. McBride at Oak Ridge National Laboratory (ORNL) and his colleagues looked at the uranium and thorium content of fly ash from coal-fired power plants in Tennessee and Alabama. To answer the question of just how harmful leaching could be, the scientists estimated radiation exposure around the coal plants and compared it with exposure levels around boiling-water reactor and pressurized-water nuclear power plants.

The result: estimated radiation doses ingested by people living near the coal plants were equal to or higher than doses for people living around the nuclear facilities. At one extreme, the scientists estimated fly ash radiation in individuals' bones at around 18 millirems (thousandths of a rem, a unit for measuring doses of ionizing radiation) a year. Doses for the two nuclear plants, by contrast, ranged from between three and six millirems for the same period. And when all food was grown in the area, radiation doses were 50 to 200 percent higher around the coal plants.

McBride and his co-authors estimated that individuals living near coal-fired installations are exposed to a maximum of 1.9 millirems of fly ash radiation yearly. To put these numbers in perspective, the average person encounters 360 millirems of annual "background radiation" from natural and man-made sources, including substances in Earth's crust, cosmic rays, residue from nuclear tests and smoke detectors.

Dana Christensen, associate lab director for energy and engineering at ORNL, says that health risks from radiation in coal by-products are low. "Other risks like being hit by lightning," he adds, "are three or four times greater than radiation-induced health effects from coal plants." And McBride and his co-authors emphasize that other products of coal power, like emissions of acid rain–producing sulfur dioxide and smog-forming nitrous oxide, pose greater health risks than radiation.

The U.S. Geological Survey (USGS) maintains an online database of fly ash–based uranium content for sites across the U.S. In most areas, the ash contains less uranium than some common rocks. In Tennessee's Chattanooga shale, for example, there is more uranium in phosphate rock.

Robert Finkelman, a former USGS coordinator of coal quality who oversaw research on uranium in fly ash in the 1990s, estimates that for the average person the by-product accounts for less than 0.1 percent of total background radiation exposure. According to USGS calculations, buying a house in a stack shadow—in this case within 0.6 mile [one kilometer] of a coal plant—increases the annual amount of radiation you're exposed to by a maximum of 5 percent. But that's still less than the radiation encountered in normal yearly exposure to X-rays.

So why does coal waste appear so radioactive? It's a matter of comparison: The chances of experiencing adverse health effects from radiation are slim for both nuclear and coal-fired power plants—they're just somewhat higher for the coal ones. "You're talking about one chance in a billion for nuclear power plants," Christensen says. "And it's one in 10 million to one in a hundred million for coal plants."

Radiation from uranium in coal might only form a genuine health risk to miners, Finkelman explains. "It's more of an occupational hazard than a general environmental hazard," he says. "The miners are surrounded by rocks and sloshing through ground water that is exuding radon."

Developing countries like India and China continue to unveil new coal-fired plants—at the rate of one every seven to 10 days in the latter nation. And the U.S. still draws around half of its electricity from coal. But coal plants have an additional strike against them: they emit harmful greenhouse gases.

With the world now focused on addressing climate change, nuclear power is gaining favor in some circles. China aims to quadruple nuclear capacity to 40,000 megawatts by 2020, and the U.S. may build as many as 30 new reactors in the next several decades. But, although the risk of a nuclear core meltdown is very low, the impact of such an event creates a stigma around the noncarbon power source.

The question boils down to the accumulating impacts of daily incremental pollution from burning coal or the small risk but catastrophic consequences of even one nuclear meltdown. "I suspect we'll hear more about this rivalry," Finkelman says. "More coal will be mined in the future. And those ignorant of the issues, or those who have a vested interest in other forms of energy, may be tempted to raise these issues again."

Fishing for Profits: Reduced Catch Means Net Gain for Fishers—And Fish

Fishing for Profits: Reduced Catch Means Net Gain for Fishers—And Fish

The more robust a given population of fish, the more money fishers can hook 

 
WHEN LESS IS MORE: Allowing fish stocks to recover actually means more profits for fishers, like the trawler pictured here.

Without fish, there can be no fishing—and such an outcome could be the future: A recent study indicates that the world's oceans appear headed toward a global collapse as overall fishing yields continue to decline dramatically, having dropped by some 10.6 million metric tons since 1994. The problem appears to be a classic "tragedy of the commons" wherein a common asset is exploited to death because no one individual has an incentive to preserve the shared resource. But, researchers report in Science that, in this case, the profit motive can be enlisted to solve this tragedy of the fisheries.

In short, economist R. Quentin Grafton at The Australian National University in Canberra and his colleagues found that, even for species that take decades to recover, reducing fishing yields in the short term boosts fishing profits in the long run. A review of four different fisheries—from fast-growing Australian northern prawn to slower growing Australian orange roughy (along with bigeye and yellowfin tuna)—showed that the highest fishing profits come from allowing these species to recover. "It's not economic to exploit fisheries to extinction," Grafton says.

Rather, the more exploited the fishery, the more economic gains to be derived from allowing it to make a comeback. Simply put: as fish become more plentiful, it costs less to catch them. "The debate is no longer whether it is economically advantageous to reduce current harvests but how fast stocks should be rebuilt," the researchers wrote.

There is a catch: "The people who reduce catch to rebuild stocks need to be the same ones that benefit by the reduced costs of fishing and higher catch per day," says fisheries scientist Ray Hillborn of the University of Washington, who participated in the analysis. "This means there must be some form of exclusive access: people who are not fishing now because it is not profitable cannot have the ability to join in the fishery when it is more profitable. If that happens then the people who pay the 'pain' don't get the 'long-term gain.'"

The researchers, therefore, argue for some form of "individual transferable quotas" (ITQs) that would give fisherfolk shares in a total allowable catch from a given fishery. Whereas a given quota could be sold to someone else, the overall total catch could not change. Such a system has been tried in Alaska and New Zealand and has led to fishery recoveries.

Although harvests would have to decline in the short term, the long term can require several decades or be as short as a few years (as in the case of Australian northern prawn). "Many of the cod stocks in Europe are overfished but still highly productive," Hillborn notes. "They would grow at 50 percent per year if fishing were completely stopped and, with a significant reduction in fishing but not total, could rebuild rather rapidly."

The researchers plan to analyze other fisheries to see if the same rule applies, but profit and property rights may prove the best tool to preserve fish worldwide. "A shift to the right target—discounted economic profits to fishers—and instruments, such as ITQs and the like, would have a huge positive impact on world fisheries," Grafton argues. It is "truly a win–win: more fish in the sea, more resilient ecosystems and much, much more profitable fisheries."

TASER Seeks to Zap Safety Concerns

TASER Seeks to Zap Safety Concerns

TASER International develops new technology, touts safety in wake of Canadian deaths possibly linked to police use

 

 
SHOCKING: The next generation of TASER—the eXtended Range Electronic Projectile (XREP)—is being designed to fire wireless probes as far as 65 feet from a half-ounce (14–gram) cartridge.

The recent deaths of three men in Canada after police stopped them in their tracks with TASER guns have resurrected the debate over use of the weapons, which utilize electric pulses and strong muscle contractions to incapacitate people considered to be a threat to officers and the public.

The three separate cases are still under investigation, but the association between them and the technology has led to misconceptions about the way these weapons affect the body, law enforcement and TASER International say.

TASERs, which represent the lion's share of all electronic-control devices used by law enforcement, work by shooting two metal probes that release electricity into the body, causing neuromuscular incapacitation. Generally, the victim feels as though "he is in a full-body charley horse," but does not lose consciousness, says Steven Ashley, a former deputy sheriff in Livingston County, Mich., who retired from the force in 1989 and is now a law enforcement consultant. "They short-circuit the electrical signals in the body."

The deaths in Canada, however, have some local politicians calling for a review of how the weapons are used, and some health care officials say these weapons are not nearly as benign as portrayed. A report released earlier this year by the Heart Rhythm Society, a Washington, D.C., organization of cardiac arrhythmia doctors and patients, found that electronic-control devices like the TASER may trigger "significant arrhythmias" in patients with pacemakers.

But Ashley, a senior master instructor for Scottsdale, Ariz.–based TASER International and an instructor for its competitor, Stinger Systems, Inc., in Tampa, Fla., disagrees that TASER weapons damage the heart or other internal organs. "The energy they emit follows the grain of the muscles and impacts sensory motion and the motor control," he says. "It doesn't go off searching for internal organs." The most common lingering effect after the muscle contractions, he says, is muscle fatigue lasting a few hours. But, he admits, "you don't know exactly how each individual will react." Other variables determining victims' injuries are how hard they fall and where they land.

TASERs contain two probes, each with a half-inch metal tip roughly the size of a fishhook that is designed to latch onto a target's body and / or clothes. The probes are packed into cartridges and are propelled at their target using compressed nitrogen. The probes travel at 180 feet (55 meters) per second when fired, spread one foot (30 centimeters) apart for every seven feet (2.1 meters) they travel and must land at least four inches (10 centimeters) from one another on the intended target to complete the circuit and channel an electric pulse into his or her body. If the probes are less than four inches apart, the TASER will deliver a shock, but not incapacitate the person.

A TASER uses up to 50,000 volts of arcing voltage to deliver a charge via the tips of its probes. Ashley, however, says TASERs are typically programmed to fire for five seconds, not enough time for a full discharge—the cycle can be stopped in less than five seconds if the weapon's safety lever is moved into the "safe" position. The high voltage is available so that a TASER's charge can reach across a gap of about two inches (or five centimeters) of air or clothing to connect with the victim's body; the probes do not have to actually penetrate skin to work. When fired, the TASER X26 weapon, a model commonly used by law enforcement, operates at 19 pulses per second at a pulse duration of 100 microseconds to deliver an average current of 2.1 milliamps. (Editor's note: in an earlier version of this story, it was mistakenly reported that a TASER has a peak current of 3 amps.) Put in perspective, a University of Illinois at Urbana-Champaign study indicates that at 20 milliamps, breathing becomes labored. At 100 milliamps, ventricular fibrillation of the heart—an uncoordinated twitching of the walls of the heart's ventricle—occurs.

"The TASER is the only weapon the police have that doesn't rely on pain compliance," Ashley says. Batons, beanbag rounds and rubber bullets can be used as nonlethal law enforcement tools, but they are only effective if a suspect ultimately surrenders. Although such weapons are often referred to as "less lethal," Ashley disagrees with this characterization. "Nothing is risk-free," he says, adding, "A TASER is not less lethal, it's nonlethal."

There are hitches. For instance, TASERs will not work properly in situations where the probes get caught in a target's clothing too far from the body to deliver a jolt, only one probe makes contact or the wires connecting the probes to the gun are damaged. "We need that tool that will absolutely incapacitate someone for 10–to–15 seconds without longterm effect," Ashley says. "TASER gets us closer to that than any other weapon has."

An investigation into the mid-October death of Robert Dziekanski, 40, at Vancouver International Airport after Royal Canadian Mounted Police used a TASER to subdue him will either confirm or contradict Ashley's view. Investigations are also underway into the deaths a month later of Robert Knipstrom, 36, in Chilliwack, British Columbia, and Howard Hyde, 45, in Dartmouth, Nova Scotia, after they were TASERed.

The technology on which current TASER weaponry is based was created in the 1970s by physicist John H. "Jack" Cover, a former director of science and engineering for the space division of aircraft maker North American Aviation (which Boeing bought in 1996). Cover's invention, however, required the use of gunpowder to discharge its probes and was considered a firearm. Cover named his invention "TASER" after a fictional weapon in Victor Appleton's 1911 adventure book Tom Swift and His Electric Rifle.

TASER International's first widely used product—the AIR TASER Model 34000, which ran on a nine-volt battery—hit the market in late 1994. When the trigger on the 34000 was pressed, it would administer a charge for 30 seconds during which the shooter could place the device on the ground and get a safe distance away from the person receiving the jolt, says Steve Tuttle, the company's vice president of communications.

For the Advanced TASER M26 that debuted in 1999, the company tweaked the number of pulses per second and their duration in order to achieve a higher level of muscle incapacitation. The goal was to do a better job of stopping individuals aggressive enough to overcome the previous model's charge, which Tuttle says stopped 84 percent of people. The M26, which ran on eight AA batteries, also recorded the time and date each time it was fired as a means of curbing misuse.

The X26 followed in 2003 and was 60 percent lighter and smaller than its predecessor, in part because it ran on two lithium ion camera batteries. In addition to having two LED lights to illuminate a target, the X26 also featured a new waveform that, Tuttle says, more efficiently delivered a shock to the body. Whereas the range of earlier TASERs was 15 feet (4.6 meters), the X26's probes could travel as far as 35 feet (10.5 meters).

The next generation TASER—the eXtended Range Electronic Projectile (XREP)—is being designed to fire wireless probes as far as 65 feet (20 meters) from a half-ounce (14-gram) cartridge that fits into any standard 12-gauge shotgun. TASER plans to start training instructors in the XREP's use by the middle of next year. Another new weapon under development is the Shockwave, which Tuttle refers to as "an area-denial system" that simultaneously fires six TASER cartridges up to 25 feet. Scheduled for availability late next year, the Shockwave is designed to be used by military and Homeland Security personnel at airports, checkpoints and other open spaces.

The company expects it will need to weather a storm of scrutiny in Canada in the coming months similar to what it experienced in 2005, when the U.S. Securities and Exchange Commission launched an informal inquiry after reports questioned the weapon's safety. That inquiry was dropped the following year.