Sparks flew when a group of hand-picked scientists debated why it is that the highly intelligent can fend off mental decline. Lisa Melton caught the action
The threat hung in the air. Ian Deary, one of the UK's top researchers into intelligence and ageing, had become disgruntled at the lack of original ideas at the Novartis Foundation meeting on the contentious concept of cerebral reserve. He could contain himself no longer. "Please say something else or I'll catch an early train back to Scotland," he snapped. Several of his peers laughed awkwardly. Deary, professor of differential psychology at Edinburgh University and organiser of the meeting, had hit a raw nerve.
The respected clinicians, epidemiologists, geneticists and psychologists who had gathered in London recently were leaders in their fields. And the very person who had summoned them to share their thoughts seemed to be angling to walk out.
The focus of their attentions was undeniably challenging. Cerebral reserve, a notional quality that gives individuals differing levels of mental resilience, has all the ingredients needed to stoke a controversy - intelligence, genes, social status, education and health. Behind it all are some widely accepted scientific results that suggest that people with high intelligence and superior education cope better with the progress of Alzheimer's disease and other forms of dementia. They also recover more rapidly from stroke, head injuries, depression and even intoxication than the average person. And while mental faculties always decline with age, there are marked differences in the rate at which the years dull the mind.
Some scientists believe cerebral reserve explains such anomalies.
Sir Michael Marmot, the epidemiologist whose groundbreaking Whitehall studies of civil servants showed how social standing affects life expectancy, was in the chair at the meeting. In typically understated manner, he had opened proceedings by acknowledging that age brings about cognitive degeneration. But he wondered about the growing evidence that education might soften the blow. "Is that what we mean by cognitive reserve?" Marmot prodded his audience. "Does it relate to something basic in the brain structure, something crude about brain size, or is it something to do with the software?" And so it started.
The group had been hand-picked. All meetings held at the Novartis Foundation's 18th-century London headquarters are invitation only and numbers are limited to up to 30 experts to encourage interaction.
Participants sit in comfortable chairs in a plain room, with no distractions other than a projector. And, in a departure from the usual format for scientific meetings, equal time is dedicated to discussion and presentation. Delegates are there to comment, critique and collude.
Exchanges can be heated, yet scientists relish the opportunity to exchange ideas with their peers. The foundation is renowned for generating scientific ruckus of the highest calibre and always attracts luminaries.
Cognitive reserve is an ideal subject for such a gathering. To some - Deary included - the concept is nothing but a chimera conjured up simply to explain a puzzling observation. So it was no surprise that Yaakov Stern, a neuroscientist at the Sergievsky Centre at Columbia University, New York, was clearly on his guard when he presented his data. He believes that brain networks are the biological underpinning of cognitive reserve. "What are people with high reserve doing differently?" he asked. His research suggests that they use alternative brain networks to compensate for those that no longer function. People with low reserve are unable to do this.
An elegant approach, but had Stern uncovered the smoking gun? His contribution sparked enthusiastic speculation among participants that, finally, here was something that might be of practical use to patients. If cognitive reserve could be measured, people could be tested for it in the same way that they are tested for, say, high blood pressure. Clinicians could then see whether a patient had strayed into the danger zone when mental decline was imminent and possibly prevent the onset of debilitating symptoms.
Cognition can be modified, neurons rearranged, by physical and mental exercises, from doing crossword puzzles to juggling. If dwindling reserve is spotted early, maybe the rate of decline could be slowed.
But others felt uncomfortable with the one-size-fits-all idea. From the back of the room, Nick Fox, a clinician scientist at the Institute of Neurology, London, who specialises in Alzheimer's disease, threw a spanner into the enthusiasts' works.
He told the meeting about a former university lecturer who had arrived at his clinic complaining of failing memory. The man's family insisted that nothing was wrong with him, and psychometric tests uncovered no problems.
But the academic was troubled. He observed that while he used to think nine moves ahead in a chess game, now he could think only five moves ahead. Some weeks later, the man died of an unrelated illness. The autopsy revealed something remarkable - his brain was riddled with the plaques and tangles typical of Alzheimer's disease. For some people, such physical damage would have reduced them to a state of confusion. For the academic it meant an impairment in his ability to play chess. "In his case, measuring cognitive reserve would not have predicted disease outcome," Fox insisted.
Deary agreed. Reinvigorated after his threat to leave had enlivened proceedings, he asked, would nuclear physicists care about a universal safety level that was set a long way below the level at which they worked? "They've got their internal threshold, which is far higher than average, and dropping to that threshold is what matters to them," he noted. The only way to be certain how an individual was doing was to track, say, how their hippocampus (the area of the brain responsible for storing information) shrank over time. Education certainly seems to make a difference. According to Marcus Richards, an epidemiologist at University College London, who has tracked people throughout their lives, educational attainment at 26 can predict cognitive ability at 53.
Deary's sceptical take on reserve seemed to infect the meeting. "Are we talking about anything other than the biology of intelligence?" he mused.
"In people's talks I tried to replace 'reserve' with 'ability' or 'intelligence' and it didn't do too much violence to what they were saying." Deary then systematically took apart every publication that claimed reserve as the explanation for a particular set of observations, demolishing the arguments.
"Is it just the case that people who peak higher have further to drop? That's not terribly profound - if you drop something from the first-floor window then it reaches the floor sooner than if you drop it from the fourth floor." Eventually, he came clean. He admitted he believed that a signature for cognitive reserve could be detected, but he acknowledged the biology behind it remained elusive. "If reserve is really getting at the biology of intelligence, then we have really very little handle on it."
Jonathan Seckl, an endocrinologist at Edinburgh, observed: "The brain is just another organ. It may be a terribly complicated one, but you can work it out." Taking an all-encompassing physiological bent, he delivered an impassioned exhortation. There was a time, he said, when heart disease was not understood - it was a black box. As a succession of risk factors such as smoking, obesity, stress and lack of exercise were uncovered, that black box faded away. Ninety per cent of heart attacks can now be explained. "I wonder whether reserve stops us thinking about what fills the black box of the brain, and what we really need to be doing is understanding all those factors that have come up today, such as genes, early life events and the adult risk factors that tell us where we are going to get with our intelligence and the rate at which it will decline." It was the meeting's epiphany. One person clapped. Others mumbled in admiration, and an incredulous voice interjected: "But that is what we're interested in!"
"Then stop calling it reserve and call it risk factors," Seckl retorted.
Sir Michael Rutter, the most influential figure in child and adolescent psychopathology over the past 35 years, had listened attentively throughout. As the proceedings drew to a close, Rutter, professor of developmental psychopathology at the Institute of Psychiatry, London, delivered a crushing verdict on cognitive reserve. "I wouldn't advise students to spend their lives measuring it," he said. "I'd pay a lot of attention to the various phenomena but I'd get rid of the concept. The research should be focused on individual differences because that's what it's about - not on some hypothetical construct of reserve."
Society is faced with an ageing population, and dementia and Alzheimer's will become more common. Any way in which such a fate can be avoided will have enormous implications. So despite some scepticism, cognitive reserve will remain high on the public health agenda. As Stern pointed out: "This is as powerful as any drug we will ever have to prevent progression of Alzheimer's disease."
At least the discussion had been gripping enough to persuade Deary to stay until the very end.