Memory: The New Sex
Better focus naturally feeds the desire for better memory. “Already, you go to dinner parties and the middle-aged high achievers talk more about how bad their memories are than about real estate,” New York Times columnist David Brooks wrote in an op-ed piece last year. For baby boomers as stressed by memory lapses as they are by erectile dysfunction, Brooks suggests, memory enhancers could be the new Viagra, and memory could be the new sex.
Think of millions of workers in India or China cognitively enhanced with neuropharmaceuticals. Will the United States be able to compete
Some existing memory enhancers appear to work, to a degree. Donepezil (Aricept) can slow the progress of mild to moderate Alzheimer’s disease by blocking the breakdown of acetylcholine, a neurotransmitter that carries messages between nerve cells. For patients with deficits, the drug improves memory, attention, reason, language, and the ability to perform simple tasks—for a time.
In normal people, the results are mixed. A U.S. study of healthy young and older subjects who took donepezil for only 14 days found that performance on short-term memory tasks actually deteriorated slightly. But a German study looked at the performance of healthy young male subjects who took the drug for 30 days and found that it selectively improved immediate recall in a verbal memory test and improved immediate and delayed recall on visual tasks.
Better memory boosters now in clinical trials should be here in four to five years. Among the most promising are the ampakines, a class of compounds that keep glutamate receptors open longer, allowing more of that critical neurotransmitter to enter the cell. Cortex Pharmaceuticals in Irvine, California, the company spearheading much of the work, reports that the compounds can slow or even halt neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s.
According to neuroscientist Mark Varney, president and CEO of Cortex, ampakines have applications far beyond Alzheimer’s. The company has shown that one ampakine compound, dubbed CX717, had a positive effect on adults suffering from ADHD. This year another version of the compound will be tested for treating ADHD.
Preliminary studies of ampakines on healthy human subjects have shown small to moderate improvements in their performance on memory tests. “Enhancing memory may be like tuning a car that’s working well,” Varney says. “You can tune it only up to a certain point. In the late teens and early twenties memory is probably at its best, so you may not get much improvement. But as people get older, certain neurons die and there is reduced capacity, so these types of drugs may help.”
While Cortex’s drugs boost the strength of neural transmissions, another company, Helicon Therapeutics of San Diego, says it can manipulate the underlying biochemistry of memory formation. Memories are created through physical and chemical changes in synapses, the connections between brain cells that are continually remodeled in the ongoing storage and retrieval of information. That process varies depending on whether the memories are poised to be long-term or just temporary, held in place for the moment but ultimately discarded to make room for something new. If a drug could boost the transformation of short-term memory to long-term memory, it could help humans absorb and retain information with considerably less practice and commitment of time.
The key insight for building such drugs came to Tim Tully, founder and chief science officer of Helicon, when his team at Cold Spring Harbor Laboratory on Long Island stumbled upon the molecular switch: a gene called CREB, which is involved in converting short-term memories into long-term ones. Molecules that modulate the CREB pathway, increasing the gene’s quantity or output, could therefore be ideal memory drugs.
Helicon has since found several CREB-modulating compounds, experimental drugs with names like HT-0712 and HT-2157. Preliminary studies point to success. In one trial, it took monkeys only 12 days to attain a score of 85 percent accuracy on memorization tests when given the drugs, compared with 24 days to attain the same level without the drugs.
A small study in healthy humans found improvement in long-term memory there, too: Subjects were asked to try to memorize a list of 10 words and recall them seven hours later and again a week later. The researchers found that treated subjects experienced only a 2 percent loss of memory over the week, compared with a 20 percent loss for untreated controls. Helicon completed a larger human trial of the drug to test for safety in 2008 (results are not yet available) and plans another trial this year.
“These drugs reduce the amount of practice needed to commit information to long-term memory. That could make them particularly helpful in shortening the effort,” Tully says.
Even successful memory enhancers may come with a downside, however. One potential problem, says psychopharmacologist Reinoud de Jongh of Erasmus University in Rotterdam, is the trade-off between long-term memory and working memory, what you hold in your brain while performing a task. For example, the prefrontal cortex (involved in working memory) and the horseshoe-shaped hippocampus (involved in long-term memory) might have opposite chemical needs. Some drugs might help keep memories fixed and thus enhance long-term storage of information. But working memory needs to be continually updated and so calls for erasure of information.
Animal studies show what can happen when a memory becomes too stable: In food-storing birds, it was possible to enhance their long-term memory for the location of their hidden food supply. When the food supply was moved, though, the birds kept searching in the old location.
Most of us have experienced the phenomenon of having a song stuck in our head. But an annoying Neil Diamond tune inexplicably playing in your brain for a while is nothing compared with reports from a handful of people who cannot forget at all.
Take the case of Jill Price, 44, who can recall minute details from every day of her life since she was 14, including what time she woke up, where she went, what she ate. Diaries she has kept since childhood show she remembers accurately, too. The condition is so rare it only recently received a label, hyperthymestic syndrome (from the Greek thymesis, meaning “remembering,” and hyper, “more than normal”). Neuroscientists at the University of California at Irvine have tested Price’s abilities and believe her phenomenal memory may be the result of a neurodevelopmental disorder.
Could some brain boosters cause a similar nightmare, making everything in your life unforgettable, including the most mundane parts? That could be a problem with future enhancers that aim to make it easier to learn by making long-term memories more enduring, de Jongh warns.
