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Simple questionnaire predicts unprotected sex, binge drinking

Valerie Reyna and Evan Wilhelms developed a new questionnaire for predicting who is likely to engage in risky behaviors, including, unprotected sex and binge drinking. Their questionnaire significantly outperforms 14 other gold-standard measures frequently used in economics and psychology.


  Study challenges model of Alzheimer's disease progression 

 The research of Professor Nathan Spreng and his collaborators sheds light on the basal forebrain region, where the degeneration of neural tissue caused by Alzheimer’s disease appears before cognitive and behavioral symptoms emerge.


 Social media boosts remembrance of things past

A new study – the first to look at social media’s effect on memory – suggests posting personal experiences on social media makes those events much easier to recall.


Experts Address Elder Financial Abuse as Global Problem

Financial exploitation of older people by those who should be protecting them results in devastating health, emotional and psychological consequences. International elder abuse experts met at Weill Cornell Medicine to map out a strategy for conducting research on this problem.


For kids, poverty means psychological deficits as adults

Childhood poverty can cause significant psychological deficits in adulthood, according to a sweeping new study by Professor Gary Evans. The research, conducted by tracking participants over a 15-year period, is the first to show this damage occurs over time and in a broad range of ways.


STUDENTS IN THE NEWS

Miss New York Camille Sims fights for social justice     

Camille Sims '15 says fate brought her to Cornell and the Department of Human Development. And now it has propelled her to reign as Miss New York and to finish second runner-up in September's Miss America competition.


Summer Scholar Spotlight: Brian LaGrant ‘17       

Brian LaGrant ’17, a human development major from New Hartford, N.Y., discusses his research on factors surrounding imitation among children and adults.


Risky decisions and concussions

David Garavito, graduate student in the Law, Psychology, and Human Development Program, under the supervision of Dr. Valerie Reyna, is working with communities in New York and around the country with support from an Engaged Cornell grant for student research. He is working with coaches and student athletes to study the effects of concussions on decision making about risks.


ARTICLES ON THE WEB

Alzheimer’s early tell: The language of authors who suffered from dementia has a story for the rest of us

Adrienne Day writes about how Barbara Lust, professor in Human Development, and other researchers are studying changes in language patterns in early Alzheimer’s disease.


 MULTIMEDIA

Listen to Associate Professor Corinna Loeckenhoff discuss self-continuity, or our perceived connections with our past and future selves.


Hear Professor Adam Anderson talk about his research in the podcast, "Brain waves: The science of emotion" for The Guardian.

In the early 1990s, Iris Murdoch was writing a new novel, as she’d done 25 times before in her life. But this time something was terribly off. Her protagonist, Jackson, an English manservant who has a mysterious effect on a circle of friends, once meticulously realized in her head, had become a stranger to her. As Murdoch later told Joanna Coles, a Guardian journalist who visited her in her house in North Oxford in 1996, a year after the publication of the book, Jackson’s Dilemma, she was suffering from a bad writer’s block. It began with Jackson and now the shadows had suffused her life. “At the moment I’m just falling, falling … just falling as it were,” Murdoch told Coles. “I think of things and then they go away forever.”

Jackson’s Dilemma was a flop. Some reviewers were respectful, if confused, calling it “an Indian Rope Trick, in which all the people … have no selves,” and “like the work of a 13-year-old schoolgirl who doesn’t get out enough.” Compared to her earlier works, which showcase a rich command of vocabulary and a keen grasp of grammar, Jackson’s Dilemma is rife with sentences that forge blindly ahead, lacking delicate shifts in structure, the language repetitious and deadened by indefinite nouns. In the book’s final chapter, Jackson sits sprawled on grass, thinking that he has “come to a place where there is no road,” as lost as Lear wandering on the heath after the storm.

Iris Murdoch and John Bayley

Iris Murdoch and her husband, John Bayley

Two years after Jackson’s Dilemma was published, Murdoch saw a neurologist who diagnosed her with Alzheimer’s disease. That discovery brought about a small supernova of media attention, spurred the next year by the United Kingdom publication of Iris: A Memoir of Iris Murdoch (called Elegy for Iris in the United States), an incisive and haunting memoir by her husband John Bayley, and a subsequent film adaptation starring Kate Winslet and Judi Dench. “She is not sailing into the dark,” Bayley writes toward the end of the book. “The voyage is over, and under the dark escort of Alzheimer’s, she has arrived somewhere.”

In 2003, Peter Garrard, a professor of neurology, with an expertise in dementia, took a unique interest in the novelist’s work. He had studied for his Ph.D. under John Hodges, the neurologist who had diagnosed Murdoch with Alzheimer’s. One day Garrard’s wife handed him her copy of Jackson’s Dilemma, commenting, “You’re interested in language and Alzheimer’s; why don’t you analyze this?” He resolved he would do just that: analyze the language in Murdoch’s fiction for signs of the degenerative effects of Alzheimer’s.

Researchers believe cognitive impairment begins well before signs of dementia are obvious to outsiders.

Prior to his interest in medicine, Garrard had studied ancient literature at Oxford, at a time when the discipline of computational language analysis, or computational linguistics, was taking root. Devotees of the field had developed something they called the Oxford Concordance Program—a computer program that created lists of all of the word types and word tokens in a text. (Token refers to the total number of words in a given text, and the type is the number of different words that appear in that text.) Garrard was intrigued by the idea that such lists could give ancient literature scholars insight into texts whose authorship was in dispute. Much as a Rembrandt expert might examine paint layers in order to assign a painting to a forger or to the Old Master himself, a computational linguist might count word types and tokens in a text and use that information to identify a work of ambiguous authorship.

Garrard had the idea to apply a similar computational technique to books by Murdoch. Alzheimer’s researchers believe cognitive impairment begins well before signs of dementia are obvious to outsiders. Garrard thought it might be possible to sift through three of Murdoch’s novels, written at different points in her life, to see if signs of dementia could be read between the lines.

Scientists believe Alzheimer’s disease is caused by cell death and tissue loss as a result of abnormal build up of plaques and tangles of protein in the brain. Language is impacted when the brain’s Wernicke’s and Broca’s areas, responsible for language comprehension and production, are affected by the spread of disease. Language, therefore, provides an exceptional window on the onset and development of pathology. And a masterful writer like Murdoch puts bountiful language in high relief, offering a particularly rich field of study.

The artist, in fact, could serve science. If computer analysis could help pinpoint the earliest signs of mild cognitive impairment, before the onset of obvious symptoms, this might be valuable information for researchers looking to diagnose the disease before too much damage has been done to the brain.

Barbara Lust,  Professor of Human Development, Linguistics, and Cognitive Science at Cornell University, who researches topics in language acquisition and early Alzheimer’s, explains that understanding changes in language patterns could be a boon to Alzheimer’s therapies. “Caregivers don’t usually notice very early changes in language, but this could be critically important both for early diagnosis and also in terms of basic research,” Lust says. “A lot of researchers are trying to develop drugs to halt the progression of Alzheimer’s, and they need to know what the stages are in order to halt them.”

Before Garrard and his colleagues published their Murdoch paper in 2005, researchers had identified language as a hallmark of Alzheimer’s disease. As Garrard explains, a patient’s vocabulary becomes restricted, and they use fewer words that are specific labels and more words that are general labels. For example, it’s not incorrect to call a golden retriever an “animal,” though it is less accurate than calling it a retriever or even a dog. Alzheimer’s patients would be far more likely to call a retriever a “dog” or an “animal” than “retriever” or “Fred.” In addition, Garrard adds, the words Alzheimer’s patients lose tend to appear less frequently in everyday English than words they keep—an abstract noun like “metamorphosis” might be replaced by “change” or “go.”

Researchers also found the use of specific words decreases and the noun-to-verb ratio changes as more “low image” verbs (be, come, do, get, give, go, have) and indefinite nouns (thing, something, anything, nothing) are used in place of their more unusual brethren. The use of the passive voice falls off markedly as well. People also use more pauses, Garrard says, as “they fish around for words.”

In their 2005 paper, Garrard and colleagues point out that the assessment of language changes in Alzheimer’s patients was based in many cases on standardized tasks such as word fluency and picture naming, the kind of tests criticized for lacking a “real-world validity.” But writing novels is a more naturalistic activity, one done voluntarily and without knowledge of the disease. That eliminates any negative or compensatory response that a standardized test might induce in a patient. With Murdoch, he and his colleagues could analyze language, “the products of cognitive operations,” over the natural course of her novel-writing life, which stretched from her 30s to 70s. “I thought it would be fascinating to be able to show that language could be affected before the patient or anyone else was aware of symptoms,” Garrard says.

For his analysis of Murdoch, Garrard used a program called Concordance to count word tokens and types in samples of text from three of her novels: her first published effort, Under the Net; a mid-career highlight, The Sea, The Sea, which won the Booker prize in 1978; and her final effort, Jackson’s Dilemma. He found that Murdoch’s vocabulary was significantly reduced in her last book—“it had become very generic,” he says—as compared to the samples from her two earlier books.

The Murdoch paper by Garrard and his colleagues proved influential. In Canada, Ian Lancashire, an English professor at the University of Toronto, was conducting his own version of textual analysis. Though he’d long toiled in the fields of Renaissance drama, Lancashire had been inspired by the emergence of a field called corpus linguistics, which involves the study of language though specialized software. In 1985, he founded the Center for Computing in the Humanities at the University of Toronto. (Today Lancashire is an emeritus professor, though he maintains a lab at the University of Toronto.)

What he discovered astounded him: Agatha Christie’s use of vocabulary had “completely tanked.”

In trying to determine some sort of overarching theory on the genesis of creativity, Lancashire had directed the development of software for the purpose of studying language through the analysis of text. The software was called TACT, short for Textual Analysis Computing Tools. The software created an interactive concordance and allowed Lancashire to count types and tokens in books by several of his favorite writers, including Shakespeare and Milton.

Lancashire had been an Agatha Christie fan in his youth, and decided to apply the same treatment to two of Christie’s early books, as well as Elephants Can Remember, her second-to-last novel. What he discovered astounded him: Christie’s use of vocabulary had “completely tanked” at the end of her career, by an order of about 20 percent. “I was shocked, because it was so obvious,” he says. Even though the length of Elephants was comparable to her other works, there was a marked decrease in the variety of words she used in it, and a good deal more phrasal repetition. “It was as if she had given up trying to find le mot juste, exactly the right word,” he says.

Lancashire presented his findings at a talk at the University of Toronto in 2008. Graeme Hirst, a computational linguist in Toronto’s computer science department, was in the audience. He suggested to Lancashire that they collaborate on statistical analysis of texts. The team employed a wider array of variables and much larger samples of text from Christie and Murdoch, searching for linguistic markers for Alzheimer’s disease. (Unlike Murdoch, Christie was never formally diagnosed with Alzheimer’s.)

The Toronto team, which included Regina Jokel, an assistant professor in the department of Speech-Language Pathology at the University of Toronto, and Xuan Le, at the time one of Hirst’s graduate students, settled on P.D. James—a writer who would die with her cognitive powers seemingly intact—as their control subject. Using a program called Stanford Parser, they fed books by all three writers through the algorithm, focusing on things like vocabulary size, the ratio of the size of the vocabulary to the total number of words used, repetition, word specificity, fillers, grammatical complexity, and the use of the passive voice.

“Each type of dementia has its own language pattern, so if someone has vascular dementia, their pattern would look different than someone who has progressive aphasia or Alzheimer’s,” says Jokel. “Dementia of any kind permeates all modalities, so if someone has problems expressing themselves, they will have trouble expressing themselves both orally and in writing.”

To the researchers, evidence of Murdoch’s decline was apparent in Jackson’s Dilemma. A passage from The Sea, The Sea illustrates her rich language:

The chagrin, the ferocious ambition which James, I am sure quite unconsciously, prompted in me was something which came about gradually and raged intermittently.

In Jackson’s Dilemma, her vocabulary seems stunted:

He got out of bed and pulled back the curtains. The sun blazed in. He did not look out of the window. He opened one of the cases, then closed it again. He had been wearing his clothes in bed, except for his jacket and his shoes.

It seems that after conceiving of her character, Murdoch had trouble climbing back inside of his head. According to Lancashire, this was likely an early sign of dementia. “Alzheimer’s disease ... damages our ability to see identity in both ourselves and other people, including imagined characters,” Lancashire later wrote. “Professional novelists with encroaching Alzheimer’s disease will forget what their characters look like, what they have done, and what qualities they exhibit.”

The Toronto team’s “Three British Novelists” paper, as it came to be called, influenced a number of other studies, including one at Arizona State University. Using similar software, researchers examined non-scripted news conferences of former presidents Ronald Reagan and George Herbert Walker Bush. President Reagan, they wrote, showed “a significant reduction in the number of unique words over time and a significant increase in conversational fillers and non-specific nouns over time,” while there was no such pattern for Bush. The researchers conclude that during his presidency, Reagan was showing a reduction in linguistic complexity consistent with what others have found in patients with dementia.

Brian Butterworth, a professor emeritus of cognitive neuropsychology at the Institute of Cognitive Neuropsychology at the University College London, also “diagnosed” Reagan in the mid ’80s, years before Reagan was clinically diagnosed with Alzheimer’s disease. Butterworth wrote a report comparing Reagan’s 1980 debate performance with then-President Jimmy Carter, with that of his debate performance with democratic presidential nominee Walter Mondale four years later.

“With Carter, Reagan was more or less flawless, but in 1984, he was making mistakes of all sorts, minor slips, long pauses, and confusional errors,” Butterworth says. “He referred to the wrong year in one instance.” If one forgets a lot of facts, as Reagan did, Butterworth says, that might be an effect of damage to the frontal lobes; damage to the temporal lobes and Broca’s area affects speech. “The change from 1980 to 1984 was not stylistic, in my opinion,” Butterworth says. Reagan “got much worse, probably because his brain had changed in a significant way. He had been shot. He had been heavily rehearsed. Even with all that, he was making a lot of mistakes.”

Thanks in part to the literary studies, the idea of language as a biomarker for Alzheimer’s has continued to gain credibility. In 2009, the National Institute on Aging and the Alzheimer’s Association charged a group of prominent neurologists with revising the criteria for Alzheimer’s disease, previously updated in 1984. The group sought to include criteria that general healthcare providers, who might not have access to diagnostic tools like neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, could use to diagnose dementia. Part of their criteria included impaired language functions in speaking, reading, and writing; a difficulty in thinking of common words while speaking; hesitations; and speech, spelling, and writing errors.

The embrace of language as a diagnostic strategy has spurred a host of diagnostic tools. Hirst has begun working on programs that use speech by real patients in real time. Based on Hirst’s work, Kathleen Fraser, a Ph.D. student, and Frank Rudzicz, an assistant professor of computer science at the University of Toronto, and a scientist at the Toronto Rehabilitation Institute, who focuses on machine learning and natural language processing in healthcare settings, have developed software that analyzes short samples of speech, 1 to 5 minutes in length, to see if an individual might be showing signs of cognitive impairment. They are looking at 400 or so variables right now, says Rudzicz, such as pitch variance, pitch emphasis, pauses or “jitters,” and other qualitative aspects of speech.

Few of us are prolific novelists, but most of us are leaving behind large datasets of language, courtesy of email and social media.

Rudzicz and Fraser have co-founded a startup called Winterlight Labs, and they are working on similar software to be used by clinicians. Some organizations are already piloting their technology. They hope to capture the attention of pharmaceutical companies regarding using their program to help quickly identify the best individuals to be part of clinical trials—which tends to be a very expensive and laborious process—or to help track people’s cognitive states once they’ve been clinically diagnosed. They also hope one day to be able to use language as a lens to peer into people’s general cognitive states, so that researchers might gain a clearer understanding of everything from depression to autism.

Lust and other researchers agree, however, that the idea of using language as a biomarker for Alzheimer’s and other forms of cognitive impairment is still in its early stages. “We ultimately need some kind of low-cost, easy-to-use and noninvasive tool that can identify someone who should go on for more intensive follow-up, such as a cup on your arm can detect high-blood pressure that could indicative of heart disease,” says Heather Snyder, a molecular biologist and Senior Director of Medical and Scientific Operations at the Alzheimer’s Association. “At this point we don’t have that validated tool that tells us that something is predictive, at least to my knowledge.”

Howard Fillit, the founding executive editor and chief scientific officer of the Alzheimer’s Drug Discovery Foundation, says language is a valid way to test for Alzheimer’s disease and other forms of dementia. “If someone comes in complaining of cognitive impairment, and you want to do a diagnostic evaluation and see how serious their language problem is, I can see that [such software] would be useful,” he says. But he says the language analysis would have to be performed with other tests that measure cognitive function. “Otherwise,” Fillit says, “you might end up scaring a lot of people unnecessarily.”

One of the main reasons Garrard undertook the Murdoch study in the early 2000s was he saw her novels as a kind of large, unstructured dataset of language. He loved working with datasets, he says, “to see whether they tell a story or otherwise support a hypothesis.” Now, with computer programs that analyze language for cognitive deficits on the horizon, the future of Alzheimer’s diagnosis looks both beneficial and unnerving. Few of us are prolific novelists, but most of us are leaving behind large, unstructured datasets of language, courtesy of email, social media, and the like. There are such large volumes of data in that trail, Garrard says, “that it’s going to be usable in predicting all sorts of things, possibly including dementia.”

Garrard agrees a computer program that aids medical scientists in diagnosing cognitive diseases like Alzheimer’s holds great promise. “It’s like screening people for diabetes,” he says. “You wouldn’t want to have the condition, but better to know and treat it than not.”

Adrienne Day is a Bay Area-based writer and editor. She covers issues in science, culture, and social innovation.

Neuroscientist Nathan Spreng, assistant professor of human development, co-authored an opinion piece in the Huffington Post, January 29th, highlighting the urgency for dementia research and treatments due to America's rapidly aging population.

Right now, approximately 4 million people have dementia in the United States. By 2030, this number will double, costing an estimated $400 billion in care. All of this money is used not for treatment, but to provide comfort and care during a slow and ugly period of decline. Spreng and his coauthor argue that the battle against dimentia is underfunded. Read more.

By Karene Booker
Reprinted from the Cornell Chronicle, September 5, 2013

Charles Brainerd

Brainerd

Cornell researchers have developed a reliable method to distinguish memory declines associated with healthy aging from the more-serious memory disorders years before obvious symptoms emerge. The method also allows research to accurately predict who is more likely to develop cognitive impairment without expensive tests or invasive procedures.

Their results hold promise for detecting cognitive impairment early and monitoring treatment, but also have implications for healthy adults, said Charles Brainerd, professor of human development and the study’s lead co-author with Valerie Reyna, director of the Institute for Human Neuroscience and professor of human development, both in the College of Human Ecology.

Valerie Reyna

Reyna

Their research, “Dual-retrieval models and neurocognitive impairment,” appears online in the Journal of Experimental Psychology: Learning, Memory and Cognition, Aug. 26.

The memory abilities affected by cognitive impairment differ from those affected by healthy aging, the authors say, resulting in unique error patterns on neuropsychological tests of memory. Their theory-driven mathematical model detects these patterns by analyzing performance on such tests and measuring the separate memory processes used.

“With 10 or 15 minute recall tests already in common use worldwide, we can distinguish individuals who have or are at risk for developing cognitive impairment from healthy adults, and we can do so with better accuracy than any existing tools,” said Brainerd.

The notion that memory declines continuously throughout adulthood appears to be incorrect, they say. “When we separated out the cognitively impaired individuals, we found no evidence of further memory declines after the age of 69 in samples of nationally representative older adults and highly educated older adults,” said Reyna.

To develop their models, the team used data from two longitudinal studies of older adults – a nationally representative sample of older adults, the Aging, Demographics and Memory Study, and the Alzheimer’s Disease Neuroimaging Initiative – that include brain and behavioral measures as well as diagnoses for cognitive impairment and dementia.

Specifically, the researchers found that declines in reconstructive memory (recalling a word or event by piecing it together from clues about its meaning, for example, recalling that “dog” was presented in a word list by first remembering that household pets were presented in the list) were associated with mild cognitive impairment and Alzheimer’s dementia, but not with healthy aging. Declines in recollective memory – recalling a word or event exactly – were a feature of normal aging.

Over a period of between one and a half to six years, declines in reconstructive memory processes were reliable predictors of future progression from healthy aging to mild cognitive impairment and Alzheimer’s dementia, and better predictors than the best genetic marker of such diseases.

“Reconstructive memory is very stable in healthy individuals, so declines in this type of memory are a hallmark of neurocognitive impairment,” Reyna said.

Younger adults rely heavily on recollection, Brainerd said, but this method becomes increasingly inefficient throughout mid-adulthood. “Training people how to make better use of reconstructive recall as they age should assist healthy adult memory function,” he said. “Our analytical models are readily available for research and clinical use and could easily be incorporated into existing neuropsychological tests.”

The co-authors of the paper are Carlos Gomes, a graduate student in the field of human development; Anna Kenney ’11, Caroline Gross ’12 and Emily Taub ’10 of Cornell – all of whom helped conduct the research as undergraduates in Brainerd’s lab; and Nathan Spreng, assistant professor of human development and Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow in the College of Human Ecology.

The research was supported in part by the National Institutes of Health and the CAPES Foundation, a federal agency under Brazil’s Ministry of Education.

Karene Booker is extension support specialist in the Department of Human Development.

By Karene Booker
Reprinted from Cornell Chronicle, September 19, 2013

Network of brain regions, highlighted in red and yellow, show atrophy in both healthy aging and neurodegenerative disease. The regions highlighted are susceptible to normal aging and dementia.

Brain regions associated with memory shrink as adults age, and this size decrease is more pronounced in those who go on to develop neurodegenerative disease, reports a new study published Sept. 18 in the Journal of Neuroscience (Vol. 33:38). The volume reduction is linked with an overall decline in cognitive ability and with increased genetic risk for Alzheimer’s disease, the authors say.

“Our results identify a specific pattern of structural brain changes that may provide a possible brain marker for the onset of Alzheimer’s disease,” said Nathan Spreng, assistant professor of human development and the Rebecca Q. and James C. Morgan Sesquicentennial Faculty Fellow in Cornell’s College of Human Ecology.

The study is one of the first to measure structural changes in a collection of brain regions – not just one single area – over the adult life course and from normal aging to neurodegenerative disease, said Spreng, who co-authored the study with Gary R. Turner of York University in Toronto.

Overall, they studied brain data from 848 individuals spanning the adult lifespan, using data from the Open Access Series of Imaging Studies and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). About half of the ADNI sample was assessed multiple times over several years, allowing the researchers to measure brain changes over time and determine who did and did not progress to dementia.

The researchers found that brain volume in the default network (a set of brain regions associated with internally generated thoughts such as memory) declined in both healthy and pathological aging. The researchers noted the greatest decline in Alzheimer’s patients and in those who progressed from mild cognitive impairment to Alzheimer’s disease. Reduced brain volumes in these regions were associated with declines in cognitive ability, the presence of known biological markers of Alzheimer’s disease and with carrying the APOE4 variant of APOE gene, a known risk factor for Alzheimer’s.

“While elements of the default network have previously been implicated in aging and neurodegenerative disease, few studies have examined broad network changes over the full adult life course with such large participant samples and including both behavioral and genetic data,” said Spreng. “Our findings provide evidence for a network-based model of neurodegenerative disease, in which progressive brain changes spread through networks of connected brain regions.”

The study, “Structural Covariance of the Default Network in Healthy and Pathological Aging,” was supported in part by the Canadian Institutes of Health Research.

Karene Booker is an extension support specialist in the Department of Human Development.

By Susan Kelley
Reprinted from Cornell Chronicle, February 11, 2013

Valerie Reyna

Reyna

Charles Brainerd

Brainerd

Defying the widely held belief that a specific gene is the biggest risk factor for Alzheimer's disease, two Cornell developmental psychologists and their colleagues report that people with that gene are more likely to develop mild cognitive impairment -- but not Alzheimer's.

The study suggests that older adults with healthy brain function can get genetic tests to predict increased risk of future mild cognitive impairment. However, once they are impaired cognitively, the tests won't predict their likelihood of developing Alzheimer's.

"Right now, genetic tests are used in exactly the opposite way. That is, healthy people don't get the tests to predict their risk of mild cognitive impairment, but impaired people get them to predict their risk of Alzheimer's disease," said Charles Brainerd, professor of human development and the study's lead co-author with Valerie Reyna, professor of human development. "So, impaired people think that tests will tell them if they are at increased risk of Alzheimer's, which they won't. And healthy people think that tests won't tell them whether they are at increased risk of cognitive impairment, which they will."

The researchers describe their findings in the January issue of Neuropsychology (27:1).

The work builds on previous research by Brainerd and associates that suggested the ε4 allele of the APOE genotype increases the risk of mild cognitive impairment as well as Alzheimer's.

The researchers analyzed data from the only nationally representative dataset of its kind, the National Institute on Aging's Aging, Demographics and Memory Study. They looked at data from 418 people over age 70 to see if those who carried the allele were more likely to develop mild cognitive impairment compared with those who did not have the allele. They also looked at whether ε4 carriers with mild cognitive impairment were more likely to develop Alzheimer's disease compared with non-carriers with mild cognitive impairment.

They found that healthy ε4 carriers were nearly three times -- 58 percent -- more likely to develop mild cognitive impairment compared with non-carriers. However, ε4 carriers with mild cognitive impairment developed Alzheimer's at the same rate as non-carriers.

While previous studies showed that the ε4 allele was more common in people with Alzheimer's disease, this study shows that it does not increase the risk that healthy or impaired people will become demented. Rather, ε4 increases the risk that healthy people will become cognitively impaired, and impaired people are the primary source of new Alzheimer's diagnoses, Brainerd explained. "The reason ε4 is a risk factor for mild cognitive impairment, but not for progression from mild cognitive impairment to Alzheimer's disease, is that this allele is a marker of initial cognitive declines -- for example, memory and executive function -- that are associated with mild cognitive impairment but not of subsequent declines in cognition or in daily functioning that are associated with forms of Alzheimer's disease."

Brainerd also noted that the effects of ε4 in healthy adults can be detected by the mid-20s. While ε4 is not a risk factor for the severe cognitive declines that signal dementia, it is risk factor for the weaker declines that eventually produce mild cognitive impairment.

The co-authors of the paper are Ronald Petersen and Glenn Smith of the Mayo Clinic; Anna Kenney '11, Caroline Gross '12 and Emily Taub '10 of Cornell -- all of whom helped conduct the research as undergraduates in Brainerd's lab; Brenda Plassman of Duke University Medical Center; and Gwenith Fisher of the University of Michigan.

The research was supported in part by the National Institutes of Health.

By John McKain
Reprinted from Cornell Chronicle, July 18, 2011
Charles Brainerd

Brainerd

Valerie Reyna

Reyna

Cornell scientists have shown a significant correlation for the first time between a human gene and people's risk for mild cognitive impairment (MCI), often a precursor to Alzheimer's disease and related forms of dementia.

The findings could help doctors to recommend simple preventative measures for at-risk patients, including healthy diet, exercise and intellectual activity -- all of which could forestall and even prevent chronic symptoms associated with the disease, said lead author Charles Brainerd and Valerie Reyna, professors of human development in Cornell's College of Human Ecology.

The professors, with researchers at the Mayo Clinic in Rochester, Minn., linked the ε4 allele of the apolipoprotein E (APOE) genotype to a greater likelihood of the onset of MCI in the July 4 issue of the journal Neuropsychology.

"We're excited about these findings, because they help identify the segment of the population who will most benefit from effective treatments to prevent Alzheimer's-type dementia," Brainerd said.

The clinical applications of linking this genetic marker with MCI are far-reaching, Brainerd said, because genetic testing can now be added to the neuropsychological tests that are currently the only way to identify MCI.

"What is at stake is whether genetic testing is useful for determining MCI susceptibility and candidacy for treatments that are designed to prevent or forestall/treat MCI (and therefore prevent Alzheimer's dementia)," the authors write. "If not, neuropsychological testing remains the only reliable means of identification."

Prior studies have been inconclusive owing to limits of their subject populations. In the new study, the researchers identified the link between the ε4 allele and the risk of MCI by analyzing a large data set from the National Institute on Aging, the Health and Retirement Study (HRS), that accurately represents older adults from all regions and racial and ethnic groups in the United States.

Classifying subtypes of MCI was also critical to the study's success. Led by Dr. Ronald C. Petersen and Glenn E. Smith at the Mayo Clinic, the authors successfully identified subtypes of MCI, only one of which is the precondition for Alzheimer's. The paper outlines how criteria for the different MCI subtypes developed by the Mayo researchers helped control for errors that have plagued previous studies that have attempted to identify an ε4-MCI link.

By sorting the HRS subjects who have the ε4 gene into subtypes of impairment identified in Petersen's and Smith's work, the Cornell researchers were able to show a significant correlation the ε4 gene and risk of the Alzheimer's precondition, known as amnestic MCI (or a-MCI). The results specifically show that 32 percent of study subjects who had been diagnosed as a-MCI were carriers of the ε4 APOE biomarker, as compared to only 20 percent of study subjects who had been diagnosed as normal and healthy.

The Cornell part of the research was supported by the National Institutes of Health.

John McKain is assistant dean for communications in the College of Human Ecology.

Related Links:
College of Human Ecology
Charles Brainerd
Valerie Reyna

By:  Aileen Costigan

CLAL members of the Alzheimer's project

CLAL members of the Alzheimer's project

A known side-effect of healthy aging is having trouble finding the right word to say. But some older adults experience more rapid decline or other language difficulties not typically found in healthy aging.

A pilot study led by Barbara Lust, professor of human development and director of the Cornell Language Acquisition Laboratory, with collaborators Dr. Janet Cohen Sherman at Massachusetts General Hospital, and Professor Suzanne Flynn at the Massachusetts Institute of Technology, suggests that older adults with early Alzheimer’s disease may be especially prone to difficulty constructing complex sentences as well as finding words. Such language problems make daily communication difficult and may also be an early marker for Alzheimer’s disease or other cognitive impairments. 

“There is a distinct gap in the research on language decline in those with clinical conditions,” said Lust.  “Several studies have raised the possibility that very early Alzheimer’s disease may be associated with deterioration in written language as seen in the works of popular authors such as Iris Murdoch. One unique contribution of our project is that we are looking at what is happening in spoken language.  Another is that we are looking at sentence formation.”

Lust and the other researchers in the Cornell Language Acquisition Lab (CLAL) and the Virtual Center for Language Acquisition (VCLA) are comparing language and cognitive abilities in three groups: healthy aging adults, adults with signs of mild cognitive impairment, and young college-aged controls. Participants are asked to repeat a series of sentences and are tested on the accuracy of their repetition. So far they have tested 40 participants and they plan to test more.

Preliminary results show that the declines found in language abilities may be separate from declines in overall cognition (e.g., memory). Specifically, those with mild cognitive impairment show particular challenges with vocabulary (e.g., word finding difficulties, word substitutions) and in certain types of complex sentence formation.

Results from this research, may shed light on the mechanisms of language decline and lead to techniques for early diagnosis and interventions for both healthy and cognitively impaired older adults.

“We are also planning to compare our findings in older adults to language development in young children,” said Aileen Costigan, project manager of the Alzheimer’s project. “If the results are the same in the young and older populations, this could help us determine how language decline is likely to occur with older adults and people with Alzheimer’s disease.  We may then know more about what to expect as the disease progresses.”

The Cornell Language Acquisition Lab, led by Lust and her collaborators, Dr. Cohen Sherman, Professor Flynn, and undergraduate Jordan Whitlock, is a collaborative, interdisciplinary group of researchers, educators, and students. Together with faculty, a talented group of undergraduate students from across the University is actively engaged in gathering and analyzing the pilot data and presenting the results in regional and national conferences.

“The Alzheimer’s language project has given me the opportunity to become deeply involved in the research process beyond what I expected as an undergraduate student. I expect to use the skills I’ve developed in data analysis, management, and interdisciplinary collaboration as I enter graduate school next year,” said Jordan Whitlock, a senior majoring in Linguistics and Cognitive Studies in the College of Arts & Sciences and planning to enter the Speech and Hearing Bioscience and Technology program at Harvard-MIT’s Division of Health Sciences & Technology.

This research is supported in part by the Cornell Bronfenbrenner Center for Life Course Development, Cornell Institute for Translational Research on Aging [CITRA] Pilot Study Program, Cornell University Cognitive Science program, Cornell University Institute for Social Sciences, and Hatch Grant/Federal Formula Funds.

Aileen Costigan, Ph.D., is the project manager of the Alzheimer’s language project and researcher in the Cornell Language Acquisition Laboratory. 

 

Jordan WhitlockIs there a way to diagnosis Alzheimer’s disease before the symptoms start?

That is the question Jordan Whitlock, a senior working with Professor Barbara Lust’s research group, is trying to answer. If an earlier diagnosis were possible, then doctors could target this incurable disease in its beginning stages, prior to the onset of severe mental decline and brain damage. The goal of Whitlock’s research is to show if language dete­rioration can be an indicator of the early stages of Alzheimer’s. She says that the “loftiest ideal of this study is to learn about the progression of Alzheimer’s without any genetic testing.”

Professor Lust’s group uses several language testing methods while conducting this study. Whitlock focuses on a technique called Elicited Imitation, where she creates sentences that slightly vary in the specific part of speech she wishes to examine. Then, she will read these sentences aloud to a subject, who will repeat it back after a few moments. Subconsciously, the subject must reconstruct the sentence in their mind before answering.  Read the full story

Karene Booker

Adapted from "Researchers Develop Simple Tools to Predict Cognitive Decline in Aging" by Lauren Gold, Cornell Chronicle, 1/26/10.

For most people, misplacing the car keys or forgetting a name is an occasional annoyance of normal aging. But sometimes forgetfulness can signal the beginning of deterioration in language, attention, reasoning, judgment or memory. With large numbers of aging baby boomers, the need for simple, accurate clinical tools that identify memory changes associated with cognitive impairment is increasingly important.

In a collaboration between Weill Cornell Medical College in New York City and Cornell's Ithaca campus, Charles Brainerd and Valerie Reyna, professors of Human Development and of Psychology, have teamed up with Dr. Cary Reid, Weill Cornell geriatrician and investigator with CITRA, on a project that will improve tools for predicting and diagnosing  memory loss.

The Cornell Institute for Translational Research on Aging (CITRA), brings together community based organizations, social scientists, and medical researchers to address pressing problems in the field of aging. The contribution of CITRA's expertise and infrastructure was pivotal in securing national support.

Now, with a two-year grant from the American Recovery and Reinvestment Act via the National Institutes of Health, the team is investigating whether a decline in a particular type of memory, called reconstructive memory, predicts cognitive impairment in the elderly. If the hypothesis bears out, it could lead to a breakthrough in our ability to detect cognitive decline years before the onset of major symptoms.

According to data from other studies, healthy elderly adults become mildly cognitively impaired at a rate of about 10 percent per year after age 70. Clinicians use a variety of neuropsychological tests to predict and diagnose the condition. However, the most reliable single test -- a basic verbal recall task in which a subject hears a sequence of words and then is asked to recall them – does not accurately predict future impairment.

That could be because people use three distinct strategies -- verbatim recall, reconstruction and familiarity judgment -- to retrieve information from memory. Earlier studies by Brainerd and Reyna have shown that verbatim recall, in which subjects mentally picture or hear the actual word, declines with age. To compensate, older adults use reconstruction, in which they remember something about the word (it was an animal, for example; or it started with the letter "p"), and then familiarity judgment, in which they sift through possible candidate words until they identify the right one. Since reconstructive memory relies on associations and experiences, which can be accessed through multiple pathways and networks in the brain, it is more robust and usually spared in healthy aging, Brainerd said.

But a decline in reconstructive memory could be an important and more accurate indicator of the extensive deterioration throughout the brain that causes cognitive impairment. To test the hypothesis, Brainerd and Reyna developed a mathematical model that analyzes data from verbal recall tests and estimates the amount a subject relies on each of the three memory processes.

In the first phase of the study, the researchers are using the model to analyze data from more than 800 previously tested adults -- some healthy and others already diagnosed with cognitive impairment -- and examining whether a decline in reconstructive memory is more closely linked with cognitive impairment among groups of people.

In the second phase, the researchers are testing and tracking 200 older adults over 18 months to see if performance in reconstructive memory predicts later emergence of impairment on an individual level. Recruitment and testing of study participants is now underway at sites in Ithaca and New York City and will gain momentum this summer as undergraduate and graduate students join the project. Dr. Reid is facilitating recruitment of study participants through the Irving Sherwood Wright Center on Aging in New York City and has been very helpful in advancing the project, said Reyna.

The findings could improve testing and treatment for impairment dramatically, Brainerd said. "Like any disease, the sooner you can identify it the better."

"The project is a model for integrating teaching and research and demonstrates the critical role of research-community infrastructure to facilitate and inform the research."

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