Starting young Decades-old IQ test records from Scottish children have opened a unique window on how the brain ages By Emily Underwood

n 4 June in 1947, just before being decoding cyphers. There were 71 questions ing and to address fears that the average released for the summer holiday, in all, with only 45 minutes to finish. Scottish was dropping as pro- 11-year-old Sheila McGowan sat down More than 70,000 other 11-year-olds took fessional families had fewer children. at her desk with a pencil and paper to the same test that day, as part of one of McGowan remembers the test “very take an intelligence test at a state-run the first efforts to measure the intelligence well,” because her mother was gravely ill school in Glasgow, Scotland. It began of an age cohort across an entire nation. when she took it. After her mom died the Oeasily enough, with simple analogies: “A Called the Scottish Mental Surveys, the following April, McGowan lived alone with man is to skin as what—coat, animal, bird, tests, including an earlier survey admin- her father, who had to work night shifts at skin or cloth—is to fur?” for example. The istered in 1932, were originally aimed at the local shipyard to make ends meet. She test quickly progressed to more difficult determining how many children were too had scored high on the intelligence test,

challenges: spatial puzzles, arithmetic, and “mentally defective” to benefit from school- but like many poor Scottish teenagers at OF ROBERTSON/UNIVERSITY DOUGLAS PHOTO: AND COGNITIVE COGNITIVE CENTRE FOR

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In April, psychologist Ian Deary (front, center) gathered not exercise, education, or any other virtu- trove of documents, having spent decades surviving members of the Lothian Birth Cohorts to ous activity, but rather simply an individu- studying the cognitive and biological ba- hear about how their brains are aging. al’s level of intelligence at age 11. As Deary sis of differences in people’s intelligence. likes to say about old age, quoting Fred He also had a personal connection to the the time, McGowan did not finish school. Astaire, “To make a success of it, you’ve got study: His uncle, Richard Deary, had partic- She went to work at 16, as a Glasgow shop to start young.” ipated in the 1932 Scottish Mental Survey, assistant. but died in World War II at age 21, when Decades passed. McGowan married and LIKE MANY COUNTRIES, Scotland’s pop- his submarine struck a mine in the Medi- had two daughters, became a teacher at ulation is aging rapidly, with the num- terranean Sea. a college for the deaf, and earned a bach- ber of people over the age of 65 pro- After unearthing the national survey elor’s degree in . Then, in 2003, jected to increase by roughly 60% over data, Deary and colleagues received U.K. a leaflet arrived at her door asking if she the next 20 years. Dozens of aging stud- charitable and government funding to had taken the 1947 mental test. The note ies worldwide are tracking seniors such as launch their new study of the participants. was from cognitive psychologist Ian Deary McGowan, looking for clues about how to Financial realities made it impractical to and his colleagues at the University of Ed- stave off cognitive decline and dementia. recontact all the survivors of the roughly inburgh in the United Kingdom. He wanted But the Lothian Birth Cohort studies remain 160,000 children who took the Scottish McGowan to take the same test again and unique thanks to an unexpected windfall. Mental Surveys in 1932 and 1947, but for participate in an ongoing study to deter- mine whether she had maintained her girl- hood sharpness or was showing signs of cognitive decline. The great divergence “It took a little bit of courage” to agree How Lothian study participants fared with age on the Scottish Mental Survey test; at age 11, to join the study, she says. Indeed, several all scores are set to zero, while gains or losses at age 70 are from the mean score of the group. of McGowan’s old schoolmates opted not to participate because they didn’t relish 25 the idea of scientists tracking their mental downswing, she says. But Deary and colleagues did persuade more than 1000 of McGowan’s contem- poraries in the Lothian region of the Scot- tish lowlands, as well as more than 500 par- 0 ticipants from the 1932 survey, to sign up for what is now a decade’s worth of follow- up studies. This April, Deary gathered as many surviving participants as possible—

the 1947 and 1932 cohorts are now 78 and Relative change intest scores 93 years old, respectively—to the Church of –25 Scotland’s Assembly Hall on the Mound in 11 70 Edinburgh for a sneak preview of the most Age (years) recent results. Roughly 400 elderly Scots attended, with one well-behaved golden re- triever in tow. In 1997, Deary and colleagues discov- one representative sample they reached out Standing before a podium under the ered records from the Scottish Mental to the nearly 5000 who lived in the Lothian Assembly Hall’s vaulted ceilings, Deary Surveys stashed away in a University of region near Edinburgh. regaled the group with the fruits of their Edinburgh basement. Boxes upon boxes of As participants rolled in, ultimately num- participation in the study, a unique look documents—containing information pains- bering 1641 from the two cohorts, they were at how childhood cognitive abilities fare takingly analyzed in the predigital age by retested on the original assessment used in across a lifetime. It has yielded more than tabulation machines that relied on punch the Scottish Mental Survey—a measure of 250 scientific publications, based on more cards and needles—had piled up in govern- IQ that has proven to be reliable and well- than 20,000 hours of cognitive tests and ment and university archives, collecting validated in both childhood and older age, brain scans, done at roughly 2- to 3-year in- dust. As they sifted through the data, Deary Deary says. The researchers also adminis- tervals. And, most significantly, it offers the and psychiatrist Lawrence Whalley realized tered a range of other cognitive and physi- beginnings of an answer to a long-debated they’d stumbled on a gold mine. “This will cal tests and took DNA samples, hoping to question: Why do some healthy people change our lives,” Whalley recalls Deary detect genetic variations that would help maintain their cognitive sharpness as they telling him at the time. explain differences in how the participants’ age, whereas others lose their edge? Although a handful of longitudinal aging mental abilities were changing with time. After studying the Lothian cohorts’ test studies can look back to IQ tests or other In 2005, Deary’s research group “upped scores on dozens of cognitive tests, sam- records of cognitive ability from age 19 to their game,” he says, after persuading the pling their genes, scanning their brains, 22 or so, “it’s very rare that we have any in- Age UK research charity to fund “The Dis- and documenting their lifestyles and health formation about the cognitive abilities of connected Mind,” an effort to perform MRI in painstaking detail for more than 10 these people at earlier ages,” notes Timothy scanning studies on 1000 of the Lothian years, Deary has found one factor that ap- Salthouse, a psychologist at the University participants. (Unlike many aging studies, pears to predict late-life cognitive ability of Virginia in Charlottesville. the Edinburgh team has no guaranteed

CREDITS: (PHOTO) IAN DEARY; (GRAPH) STUART RITCHIE AND IAN DEARY RITCHIE STUART (GRAPH) IANDEARY; (PHOTO) CREDITS: better than any other single measure. It’s Deary was well-suited to exploiting the funding, so Deary says he must find new

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Published by AAAS SPECIAL SECTION THE AGING BRAIN sources for each wave of data collection. “It age, says Paul Thompson, a neuroscientist days for research into cognitive training, takes up a lot of my time.”) at the University of Southern California Greenwood says there is growing evidence So far, the work has supported a clear (USC) in Los Angeles. In the Nun Study that activities that improve specific abili- conclusion: A large part of participants’ dif- of Aging and Alzheimer’s Disease at the ties, such as the ability to control attention, ferences in cognitive ability during these se- University of Minnesota, for example, re- may have practical benefits for reasoning nior years, as measured in relation to their searchers examined autobiographical es- and problem-solving. peers, depends on where they stood at 11. says written by Roman Catholic sisters at Indeed, although childhood IQ may be The participants’ scores at age 11 can predict the time of induction at about age 22. They the largest factor in late-life intelligence, about 50% of the variance in their IQs at age found that the linguistic complexity in the the Lothian study suggests it accounts for 77, Deary and his colleagues estimate. writing was a strong indicator of how the just half the variation—which means that A few studies elsewhere have also dem- nuns would fare in later life. Compared other factors must account for the remain- onstrated the importance of early cognitive with nuns whose essays “looked like Cicero, ing 50%. Regardless of how smart they were ability to maintaining one’s faculties with with wonderful, florid prose,” nuns whose as children, people in the Lothian cohort writing was laconic and brief were substan- who did not smoke, were physically fit, bi- tially more likely to have poor cognitive lingual, or had more education enjoyed function and Alzheimer’s disease 58 years slightly better cognitive test scores in old Tracking healthy aging later, Thompson says. age than their early life scores would have Other studies of aging have taken various By having an intelligence measure from predicted, he says. And Deary is convinced approaches to tracking cognitive change. even earlier in life, the Lothian studies that other factors, both genetic and envi- are helping distinguish glitter from gold ronmental, must also play a role in explain- in the vast literature on factors correlated ing how some people whose intelligence with cognition. A good recent example is ranked quite low as children made impres- Deary’s analysis of the potential benefits of sive strides as adults, while others “start out drinking, Thompson says. A smattering of at a high level, and end up quite low.” correlational studies suggest that drinking small amounts of wine has positive effects THIS SPRING, WHEN DEARY SPOKE to on cognition late in life—indeed, Deary ini- the study participants under the Assembly tially found a similar result when he first Hall’s vaulted ceilings, he began by teasing looked for a relationship between alcohol them. Gazing out over a sea of white hair consumption and cognitive performance in and wool cardigans, he said, “I’ve decided the Lothian cohort. When he accounted for to mix it up today, and pit the 1921s against the participants’ IQ scores on the Scottish the 1936s.” The two groups looked around Mental Survey, however, the auditorium, trying to THE NUN STUDY 1986 the perceived benefit determine who belonged Archived autobiographical essays written dissolved. Rather than in which group. Few of when women joined an order of Catholic gaining cognitive benefit the 550 people who took nuns at age 22 provide an early cognitive from drinking wine when the Scottish Mental Sur- measure for this long-term study. Many of they were older, “people vey in 1932 and enrolled the 600 sisters have agreed to donate their who drank more were al- in the study more than 60 brains to research (above) after death. ready likely to be smart,” years later were present— Deary says. they are now 93 years SWEDISH ADOPTION/TWIN STUDY The Lothian cohort has old—but the attendance OF AGING 1984 similarly challenged other of 78-year-olds from the Like several other twin studies worldwide, reported influences on larger 1947 test cohort this study of more than 2000 identical and cognition, such as diet, was more robust. “You nonidentical twins reared in separate homes body mass index, and caf- After taking an intelligence exam at can’t tell who is who, can looks at the role of genes versus environ- feine consumption. None age 11, Margaret Lawson is now among you?” Deary joked. ment in cognitive decline. of those factors seems to the 1641 Scots being studied for clues He shared the good have any effect on cogni- to how the brain ages. news first. Over the past OKINAWA CENTENARIAN STUDY 1976 tive skills in the Lothian decade of testing, both In the world’s longest running study of cohort when childhood intelligence is ac- cohorts had held up well on tests of mem- centenarians, including more than 900 counted for, Deary says. Even the effects of ory and knowledge, such as remembering people, researchers look for both genetic social and intellectual activity disappeared a paragraph-long story and pronouncing and lifestyle contributors to the unusual when he took into account how bright chil- words, though likely in part because of longevity and lucidity of the residents of dren were at age 11, possibly because those their growing familiarity with the test, Okinawa, Japan. children are more likely to end up being so- Deary says. In skills that required abstract cially and intellectually engaged. problem-solving, fast thinking, and speedy BALTIMORE LONGITUDINAL STUDY Deary’s work is “very elegant,” says Pamela reaction times, however, all groups showed OF AGING 1958 Greenwood, a psychologist at George Mason some decline with age from results in pre- More than 1000 healthy people between University in Fairfax, Virginia, but she cau- vious years. A task that required a person 20 and 60 years old are now enrolled in this tions that it does not mean mental function to quickly discriminate between two lines study of aging over the past half-century, in old age is foreordained, with no hope for of different lengths as they flashed on a returning to Baltimore every 2 years for interventions that can help boost or preserve screen was particularly challenging for all

cognitive and physical tests. one’s brainpower. Although it’s still early the participants and elicited a widespread LIBRARY WELLCOME THE RIGHT) KARENKASMAUSKI; TO (LEFT PHOTOS:

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Published by AAAS groan when Deary named of data from the Lothian it. That all participants Birth Cohort studies and seem to be struggling at other aging research sup- this task suggests age may ports a theory that some take a particular toll on describe irreverently, and the ability to quickly and a little brutally, as the “wa- efficiently sample sensory ter tank hypothesis”: The information, says Stuart better put-together your Ritchie, one of Deary’s brain is early on, thanks postdoctoral students. “A to good genes and, to fascinating thing is that some extent, a favorable decline in this simple early life environment, the sensory speed measure more cognitive reserves tracks decline in complex you have to lose to neuro- thinking skills as the co- degeneration. In other hort ages,” Deary says. words, Martin says, “the Although the averages more you start out with of the Lothian cohort re- in the tank, the longer it veal intriguing trends, takes to draw down.” Deary’s true passion is for Pinpointing the genes the study of individual di- that determine how full vergence. He flipped to a the tank is and how fast it slide that displayed how empties will take studies the cohorts’ test scores on Maps of white matter connections in the Lothian cohorts, such as this one, of a 73-year-old much larger than Deary’s. all the tests had fanned participant, suggest that better neuronal wiring in old age is linked to higher cognitive function. Neuroscientists and ge- out as people hit their 70s neticists “have learned the and 80s, with many straying far from the av- from the Lothian cohort may help unravel, hard way,” Thompson notes, that hundreds erage. “What I’m trying to do with my col- says Sherif Karama, a psychiatrist at McGill of thousands of DNA samples are required leagues is study why the mean does not tell University in Montreal, Canada. People with to make even minor inroads toward identify- you the full story,” he told the elderly Scots. Alzheimer’s disease have an undeniable thin- ing how different genetic variants affect the Brain scans of these volunteers show that ning of the cerebral cortex, but this region, brain and how such variants interact with aging takes a vastly different toll on each which is involved in nearly all the brain’s environment to affect behavior. person, notes Joanna Wardlaw, a neuro- higher level cognitive processes, such as In 2009, the Lothian studies took a radiologist at the thinking and decision-making, shrinks in first step, joining a consortium of 70 who collaborates with Deary. Using a tech- “normal” aging, too, he explains. Historically, separate institutions in 33 countries nique called diffusion tensor imaging, which scientists have assumed that when healthy called ENIGMA, which seeks to ramp up tracks how water molecules move through- older people complained of cognitive deficits, the search for genetic variants that af- out the brain’s white matter tracts, Wardlaw their cortex shrinkage was to blame, or at fect the brain. With access to brain scans and colleagues have found that roughly 10% least reflected a neurodegenerative process, and DNA from hundreds of thousands of of the differences in general cognitive func- he says. But earlier this year, Karama used people from regions as diverse as Brazil, tion in the Lothian participants depends on Lothian data to show that the people with the United States, Cambodia, and Siberia, the integrity of neuronal connections. a relatively thinner cortex in old age also researchers are already finding clusters of Certain blotchy patches of abnormal had a lower IQ both as adults and in child- genes that play a role in notoriously com- white matter, called hyperintensities, are hood. That suggests, he says, that those who plex disorders such as schizophrenia, says known to signal damage to blood vessels, appear to be losing brain mass along with Thompson, who this month received an surrounding cells, and the connections be- their cognitive abilities may simply have $11 million grant from the U.S. National tween neurons. The hyperintensities gener- started out with less gray matter. Deary and Institutes of Health to establish a Center ally increase with age but can vary drasti- colleagues have recently begun collecting of Excellence for the ENIGMA project at cally from person to person, Wardlaw says. the donated brains of Lothian participants USC. The same approach may also help un- An important goal of the Lothian study is after they die, in order to further explore tangle the genetic factors that affect cogni- to determine how hyperintensities interfere structural and anatomical differences that tive aging—for example, why some people’s with cognition, and why some people seem might explain why some people age better brains age faster than others when exposed to be more susceptible to them, whereas than others. to high levels of stress hormones, he adds. for others they seem to represent harmless Toward the end of his presentation this Sheila McGowan, for her part, has taken “wrinkles” on the brain—the neural equiva- April, Deary unfolded a slip of paper and Deary’s study as a call to action to make lent of crow’s-feet or frown lines, she adds. read a question about aging submitted by the best of her aging brain. A longtime art What causes hyperintensities is still poorly the audience: “So, are you just lucky or un- lover, she has taken up painting again and understood, but research from the Lothian lucky with the brain you’ve got?” it asked. hopes to exhibit her work one day. At age cohort and other groups suggests that they At least for now, “the short answer to 75, after joining the Lothian cohort, she are “pretty tightly linked” to high levels of that question appears to be ‘yes,’ ” says began taking online university courses fo- cortisol, a hormone released in response to Nicholas Martin, a geneticist at QIMR cused on philosophy and art history. Con- stress, USC’s Thompson notes. Berghofer Medical Research Institute in fronting the reality of her own aging brain Why the cerebral cortex tends to shrink in Herston, Australia, who is not involved “catapulted me out of my lethargy—I’m try-

IMAGE: MARK BASTIN AND DAVE LIEWALD, BRAIN RESEARCH IMAGING CENTRE, UNIVERSITY OF EDINBURGH OF UNIVERSITY CENTRE, IMAGING RESEARCH BRAIN LIEWALD, AND DAVE BASTIN MARK IMAGE: normal aging is another mystery that scans in the studies. He says the growing body ing to buck the change,” she says. ■

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