FDA-approved formoterol drug improves cognitive function in mouse model of Down syndrome

from News Medical:
An existing FDA-approved drug improves cognitive function in a mouse model of Down syndrome, according to a new study by researchers at the Stanford University School of Medicine.
The drug, an asthma medication called formoterol, strengthened nerve connections in the hippocampus, a brain center used for spatial navigation, paying attention and forming new memories, the study said. It also improved contextual learning, in which the brain integrates spatial and sensory information.
Both hippocampal function and contextual learning, which are impaired in Down syndrome, depend on the brain having a good supply of the neurotransmitter norepinephrine. This neurotransmitter sends its signal via several types of receptors on the neurons, including a group called beta-2 adrenergic receptors.

Memory training study points to possible benefits for children with Down syndrome

A study, conducted by researchers at Down Syndrome Education International and published today in the American Journal on Intellectual and Developmental Disabilities, suggests that adaptive working memory training might offer sustained benefits for young people with Down syndrome.

People with Down syndrome tend to be more limited in their abilities to store and manipulate information over short periods of time (short term and working memory) than other people.

These memory systems impact many areas of learning, including the acquisition of vocabulary, grammar and reading skills. Improving short term and working memory function might therefore be expected to have important consequences for educational outcomes.

Studies published in recent years suggest that computerised adaptive working memory training may improve memory function for children with relatively limited working memory skills.

DSE therefore set out to explore if similar results might be achieved for children with Down syndrome by conducting a randomized controlled trial of Cogmed Working Memory Training with children with Down syndrome aged between 7 and 12 years.

The study was funded by The Baily Thomas Charitable Fund and Down Syndrome Education International, and the findings are published today in the American Journal on Intellectual and Developmental Disabilities.

We found that children who undertook 25 session of computerized memory training, on average, achieved important gains in visuospatial short term memory and visuospatial working memory, compared to children not undertaking training.

This study suggests that adaptive working memory training could be a practical and useful intervention for children with Down syndrome. However, further research is required to confirm this. Future research is needed to explore if memory training can deliver improvements in verbal as well as visuospatial memory, and (importantly) if these gains subsequently lead to improvements in language, literacy and wider academic skills.

• Read more about the trial...

Use this link for a free trial of the memory training software mentioned above from DSE and Pearson Education (click here)

New genetic cause for learning disability in Down syndrome identitfied

Neurons from a normal mouse (left) are longer and fuller than neurons from a mouse lacking SNX27 (right).

By Dr. Leila Luheshi from PHG Foundation:

Researchers have reported a novel molecular mechanism through which triplication of chromosome 21 could cause deficits in learning and memory in patients with Down syndrome.
Down syndrome is caused by the abnormal inheritance of three (rather than the usual two) copies of chromosome 21.  At a genetic level this leads to higher than normal levels of expression of the many genes and non-coding RNAs that are encoded on this chromosome.  Clinically this results in a complex constellation of symptoms of which the most prominent is a varying degree of learning disability.  Learning disability in Down syndrome is associated with reductions in the number and activity of the synapses (connections) made between neurons in the brain, and so understanding the mechanisms underlying these neurodevelopmental abnormalities may provide the key to ameliorating the effects of this disorder.

A new study in Nature Medicine reports that the protein encoded by the sorting nexin 27 (SNX27) gene, which is present at abnormally low levels in the brain of patients with Down syndrome, may underlie the presence of learning disabilities in this condition. 

The researchers showed, by knocking out the Snx27 gene in mice, that its expression is vital for brain development.  In particular they discovered that Snx27 is vital for the maintenance of synaptic activity and consequently for learning and memory, deficits in which underlie learning disability in patients with Down syndrome.  In a key experiment that linked these observations in mice more directly with the symptoms of Down syndrome in humans, the team were able to demonstrate that increasing Snx27 levels in a mouse model of Down syndrome could reverse the learning and memory deficits from which it is suffers.  

'Cough syrup' could help people with Down syndrome

by Sarah Dingle from ABC Australia:
An ingredient in cough mixture could hold the key to improving language skills for people with Down syndrome.
Researchers from Monash University believe BTD-001 - an ingredient in cough syrup which was first discovered in the 1920s - could improve the memory, language and learning of people with the condition.
Associate Professor Bob Davis, who is the head of the centre for Developmental Disability Health at Monash University, says throughout the last century BTD-001 has been prescribed for everything from persistent coughs to Alzheimer's disease.
"In the 1950s and 60s it was used ... as an ingredient for a drug for people with dementia," he said.
"People with dementia seemed to improve their memory and ... cognitive ability, so the ability to think.
"At that stage the medication had been shown to be safe and while there were some small studies indicating that it seemed to work, it didn't have the large drug trials that are required nowadays."
Since then, Prof Davis says it has been established that BTD-001 improves the conductivity of the nerves in the brain.
He says a US research foundation discovered that in comparison to the general population, the nerves in people with Down syndrome have less conductivity and a diminished ability to store information.
His study, which is based in Australia and New Zealand, is aimed at identifying how memory and cognitive ability is affected by the medication.
Catherine McAlpine, head of Down Syndrome Australia, welcomes the research but has some reservations.
"There are very few research projects into helping people with Down syndrome and the primary area of research is in prenatal testing which has its own ethical boundaries and ethical issues," she said.
"Clearly, if we can do things that help people with Down syndrome be more independent, then that's a good thing for everyone.
"But it can be a little bit complicated when we are talking about quality of life and increased cognition being one and the same because they're not the same thing."
There are about 6 million people with Down syndrome worldwide.

Yoga for Girls with Down Syndrome

from the Windsor Star by Kelly Steele:
For Windsor’s Nicole Daignault, teaching yoga is more than just poses and deep breathing. It’s a chance to share her love with others.
That’s why Daignault started Yoga for Exceptional Girls at Windsor Squash and Fitness Club. The class is geared to girls 12 years of age or older who have Down syndrome. Daignault, who goes by the nickname Coco, admits she is excited to see the girls and women sharing her love.
“It’s the first time I’ve done something specific to a special-need group,” she said. “However, over the years I’ve had the pleasure of having several people come into my classes with various special needs. I’ve taught wheelchair-specific yoga, people with Down syndrome, multiple sclerosis and quite elderly people.
“I really love to do those special group classes where they come to realize that yoga isn’t just all about these big fancy moves, but that everyone can do it,” she said. “It’s inspired me over the years to work with those groups.”
It was a class Daignault taught this summer that got the wheels turning.
“One girl who participated in the group class had Down syndrome,” she said. “She did everything. I was very inspired by that and she never left my mind.”
When she returned from vacation, the owners of Windsor Squash and Fitness asked Daignault about her plans for the yoga program.
“I knew I wanted to work with this group,” she said. “I know what it’s like to be a 12-plus girl and I know what it’s like to be a 12-plus girl with physical problems.”
Daignault was born with scoliosis, an abnormal curving of the spine which has caused a lot of pain and problems over the years. She also has leg-length discrepancy, which caused her to walk with a limp into her early 20s.
“People with Down syndrome seem to have overly unstable joints,” she said. “So the yoga is, for them, much more for the strengthening and stabling of their joints. They are very flexible. But the feet, knees, hips need stabilizing, and add on slower metabolism and weight gain, it just exacerbates what’s going on.”
Studies have shown yoga is beneficial for people with Down syndrome because it helps them improve muscle tone, flexibility and balance while promoting a sense of inner peace. Yoga poses may also help internal organs and rejuvenate the endocrine glands. Simple breathing exercises may help calm and restore the nervous system.
For children with Down syndrome, yoga helps bring body awareness and increases concentration and memory skills.
“I tweak what I normally do in my classes,” said Daignault, who’s been teaching for 13 years. “One thing I bring into the class for them is rhythm. Keeping consistency for people with Down syndrome is also important. They need regular routines and patterns.
“We have a set pattern as to what we will be doing. The poses may change a bit. But we will be starting the classes off with drum beat rhythm to help them get the beat of their breathing. Less on the flexibility, more on the strengthening and stability.”
Sound therapy includes chanting, mantras and drumming. Sound vibrations have healing qualities and children respond readily to any activities involving instruments or singing. For that reason, Daignault incorporates the drum beats into her program.
She has six people in her class, ranging in age from 14 to 22, and everyone seems to be embracing yoga.
“There are always obstacles, everyone has their own internal problems,” she said. “Balance is a problem. They will go to the wall to balance themselves.”
Daignault loves sharing her skills with the class. “Yoga builds community in general, ” she said. ” People make friends and you start to get involved in the yoga community. My hope is that not only do they build nice friendships here but I’d love them to ultimately have the basics they need to go into any yoga class.”
For more information, visit windsorsquash.ca
ksteele@windsorstar.com

Prenatal intervention reduces learning deficit in mice

from Science Codex:
Mice with a condition that serves as a laboratory model for Down syndrome perform better on memory and learning tasks as adults if they were treated before birth with neuroprotective peptides, according to researchers at the National Institutes of Health.
Down syndrome results when an individual receives an extra copy of chromosome 21. According to the Centers for Disease Control and Prevention, Down syndrome occurs in 1 of every 691 births. Features of Down syndrome include delays in mental and physical development and poor muscle tone. These features may vary greatly, ranging from mild to severe.
The researchers studied growth factors that are important at certain key stages of brain development in the womb. Named for the first three amino acids making up their chemical sequence, NAP and SAL, are small peptides (small protein sub units) of two proteins. These two proteins enhance the ability of brain cells to receive and transmit signals, and enable them to survive. (NAP is an abbreviation for NAPVSIPQ and SALfor SALLRSIPA.)
The mice in the study had an extra copy of mouse chromosome 16, which has mouse counterparts to 55 percent of the genes on human chromosome 21.The researchers treated pregnant mice with NAP and SAL for five days, then tested the mouse offspring at 8 to 12 months of age, comparing them to mice treated with a saline solution (placebo). Mice with the extra chromosomal material that were treated with NAP and SAL in the womb learned as well as mice that did not have the extra chromosome, and significantly faster than mice with the extra chromosome that were treated with saline solution.
"Our study has provided important information that may help in the understanding of Down syndrome," said senior author Catherine Y. Spong, M.D., chief of the unit on perinatal and developmental neurobiology at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute where the research was conducted.
Dr. Spong collaborated with first author Maddalena Incerti, M.D., Kari Horowitz MD, Robin Roberson, Daniel Abebe, Laura Toso, M.D., and Madeline Caballero, all of the NICHD Unit on Perinatal and Developmental Neurobiology. Dr. Incerti also is affiliated with the University of Milano-Bicocca, Italy, and Dr. Horowitz now is affiliated with the University of Connecticut, Farmington.
Their findings appear online in PLOS ONE.
In an earlier study, Dr. Spong and her colleagues found that, if treated with NAP and SAL in the womb, mice with the extra copy of chromosome 16, achieved developmental milestones earlier than did mice with an extra copy of chromosome 16 that had not been treated. In that study, the researchers examined developmental milestones for sensory, motor skill, and muscle tone development in the first three weeks of life.
"In our earlier work, we showed that treating the mice during pregnancy could prevent developmental delay as assessed with milestones," Dr. Spong said. "In this study, we showed that treatment with NAP and SAL not only puts the animals on a typical developmental trajectory, it also improves their ability to learn.
For the current study, pregnant mice received injections of the two protein fragments starting eight days after conception. This is equivalent to the end of the first trimester in a human pregnancy.
The researchers tested the learning skills of the mice when the animals reached adulthood. The mice were placed in a tank of water on a clear platform. The tank had symbols on each wall that the mice could use to orient themselves. Researchers then placed the mice directly in the water and timed how long it took them to locate the platform. With repeated trials, the mice become more adept at the task and take less time to reach the platform.
Over five days of testing, the researchers found that the time spent searching for the platform decreased substantially for all groups except the mice with the extra copy of chromosome 16 that were not treated with NAP and SAL in the womb.
The research of Dr. Spong's team is part of an NIH-wide focus on Down syndrome outlined in a 2007 Down syndrome research plan. The plan highlights research priorities for the field, including establishing a Down syndrome patient registry, which was announced Oct. 25, 2012.

Source: NIH/National Institute of Child Health and Human Development

Parents of kids with Down syndrome following US researcher’s ‘memory drug’

by Karl Stagno-Navarra from Malta Today:

Despite the still embryonic stages of the drug, a number of parents from all over the world – including Malta – have contacted this doctor asking whether they should give their children the drug.

A number of Maltese parents of children affected by Down Syndrome, have reportedly been in contact with Alberto Costa, a Brazilian-born associate professor of medicine and neuroscience at the University of Colorado-Denver Anschutz Medical Campus, who has recently discovered a drug might help the memory of people with the condition.

The breakthrough drug called 'memantine' has so far produced what has been described as "cautiously encouraging results".

Despite the still embryonic stages of the drug, a number of parents from all over the world - including Malta - have contacted Costa asking whether they should give their children the drug.

He says no. It's still an experimental drug whose long-term effects are unknown. "Hence, please don't try it," he tells them.

During Costa's clinical experiment, young men and women with Down Syndrome were administered for 16 weeks with memantine, which is normally used by Alzheimer patients to improve their memory.

The subjects showed statistically significant improvements in one of five key memory tests compared with others who took placebos.

Its outcome was not substantial, but enough to draw attention from the Down Syndrome community around the world, following the publication of a lengthy profile of Costa in The New York Times, who is now searching for funds in order for him to broaden his research.

Michelle Sie Whitten, executive director of the Global Down Syndrome Foundation, which has helped fund Costa's research for the past six years, said Costa made a crucial link between Alzheimer's and Down syndrome that will affect future research.

"No one, including Alberto, is jumping up and down" over the results of the clinical trial, she said, "but it showed us much more information than we had before".

Research Down Syndrome Announces 2012/2013 Grant Awards to Fund Down Syndrome Cognitive Research

by Research Down Syndrome:

Research Down Syndrome (RDS) has announced funding for six grants to support Down syndrome cognitive research. The grant total represents a fifty percent increase over grants awarded by RDS in 2011.

RDS is committed to supporting the identification of the causes of the intellectual impairments associated with Down syndrome and to facilitating the development of pharmacological therapies to improve memory, learning and communication in persons with Down syndrome. Encouraging progress has been made over a very short time. A human clinical trial was initiated in the fall of 2011, less than a decade after the support of private foundations stimulated the progress of Down syndrome cognitive research.

Research Down Syndrome, among the leading sources of private funding for Down syndrome related cognitive research, prioritizes funding towards programs with a high probability of readily contributing to the development of safe and effective therapies.  Continued private donations are needed to support the constantly expanding research efforts that will lead to potential medical treatments. The 2012/2013 RDS Research Grants include:

1. Johns Hopkins University School of Medicine:  RDS Research Center Grant entitled "A Down Syndrome Virtual Center for Basic and Translational Studies- Cognition and Therapies in Down Syndrome"    
2. University of California, San Diego School of Medicine:  RDS Research Center Grant entitled "Defining the Genes and Mechanisms Causing Neurodegeneration in Down Syndrome and Discovering Effective Treatments" - Pilot Proposal entitled "21Lab: A Collaborative Data Sharing and Data Integration Platform for the Down Syndrome Research Community"
3. University of Arizona:  RDS Innovation Research Grant entitled "The Neuropsychology of Down Syndrome"
4. Stanford University School of Medicine: RDS Innovation Research Grant entitled "Mechanisms Underlying the Roles of Sleep and Circadian Rhythms in the Learning Disability of Down Syndrome"
5. VA Palo Alto Health Care System: RDS Innovation Research Pilot Grant entitled "Improving Adrenergic Signaling for the Treatment of cognitive Dysfunction in Down Syndrome"
6. University of Texas, Austin:  RDS Innovation Research Pilot Grant entitled "Genetic Analysis of Excessive Inhibitory Signaling in Down Syndrome"

Detailed information on these grants can be found at: www.researchds.org

 

About Research Down Syndrome

Research Down Syndrome (RDS) is among the leading sources of private funding for Down syndrome related cognitive research.  RDS supports and funds Down syndrome cognitive research conducted at research institutions that are studying the basis of the intellectual impairments associated with Down syndrome, including Alzheimer's disease. Research Down Syndrome is a legal corporate entity, and is a 501(c) (3) nonprofit organization designated by the Internal Revenue Code.  For more information, go to www.researchds.org, or contact RDS:  info@researchds.org or 847.710.2251.

SOURCE Research Down Syndrome

Read more here: http://www.sacbee.com/2012/10/08/4892505/research-down-syndrome-announces.html#storylink=cpy

Drug can improve memory in patients with Down syndrome, researchers say

from the Denver Post by Michael Booth:

A long-anticipated CU study claims an Alzheimer's drug can boost memory function in Down syndrome patients, researchers announced Tuesday.

CU School of Medicine researchers said the drug memantine improved "visual episodic memory," such as retaining long lists of vocabulary words, in Down syndrome patients. The 16-week course compared the results to a control group taking only a placebo.

The study did not find improvement in two other areas of thinking, adaptive or most areas of cognitive ability.

Researchers, led by Dr. Alberto Costa, also said they must expand the study to more subjects to solidify their results, as the CU study focused on about 38 adolescents and young adults.

CU called it a major milestone.

"People who took the medicine and memorized long lists of words did significantly better than those who took the placebo," said Costa, who is a neuroscientist. "This is a first step in a longer quest to see how we can improve the quality of life for those with Down syndrome."

The Down syndrome community has been talking about Costa's research and similar efforts for years, at the same time major advances have been made in prenatal testing for the condition.

Private companies recently released a test that allows mothers to find out much earlier in their pregnancy if their child has Down syndrome. That has led families and ethicists to worry that many more people will choose abortion.

Researchers doing work to improve the cognition and condition of children born with Down syndrome have said their funding has diminished, as people assumed far fewer cases would survive to term.

Read more: Drug can improve memory in Down syndrome patients, researchers say - The Denver Post http://www.denverpost.com/breakingnews/ci_21094038/drug-can-improve-memory-down-syndrome-patients-researchers#ixzz20uCgeUeV

iPad, iPod, and iPhone apps to help early development

from Down Syndrome Education International:

Down Syndrome Education International is working with developers to create new learning opportunities for children with Down syndrome using portable devices including iPads and iPods. Recently released apps support language, memory and number skills development.

Computerised educational activities have the potential to offer significant benefits for young people with Down syndrome, with an emphasis on the visual presentation of information and opportunities to encourage lots of practice. DSE is working with partners in the UK, Europe and the US to create apps that target the developmental needs and learning styles of young people with Down syndrome. Some of the first of these apps are now available.

Special Words from Special iApps

Special Words teaches children to recognise written words, using pictures and sounds, on iPad, iPhone and iPod touch. The app has 3 games with increasing difficulty, Match Pictures, Match Words and Match Both.

Special Words comes with the vocabulary and pictures from the early steps of DSE’s See and Learn Language and Reading program, comprising of 96 written words children use in their early vocabulary.

It includes matching pictures, written and spoken words, in 8 languages: American and British English, Spanish, Catalan, French, German, Italian and Swedish. Users can easily replace the words and re-record the audio in any other language their child uses. Users can add more words, pictures and sounds for family members, friends, and familiar objects, to increase their child’s interest, and further develop their vocabulary.

Special Words was developed by Special iApps, a social enterprise founded by parents of a child with Down syndrome who have many years of experience in both education and software. Special iApps is donating a proportion of the global sales of Special Words to Down Syndrome Education International.

• Special Words on the App Store (US edition)
• Special Words on the App Store (UK edition)

 

Memory Fun and Counting Fun from Felix Education Apps

Memory Fun is a memory game where the user has to remember the position of picture cards in order to recall the location of two matching cards. Starting with just four cards to choose from, up to 18 cards can be displayed with a vocabulary of over 100 words.

Counting Fun is a simple counting game designed to encourage practising counting from 1 to 10. Sound effects and animation engage the child’s attention while they tap each item displayed on the screen to hear and see each digit.

Felix Education Apps is a family run business based in Oslo, Norway, designing educational apps. Felix Education Apps is donating a proportion of the global sales of their apps to Down Syndrome Education International.

• Memory Fun on the App Store (US Edition)
• Counting Fun on the App Store (US Edition)

Scientist tests promising drug on those with Down syndrome

from Health Canal:

A University of Colorado School of Medicine scientist is finishing a major clinical trial on a drug that could boost cognitive function in those with Down syndrome, significantly improving their quality of life and representing a potential milestone in research on this genetic disorder.

“We are hoping to enhance memory and learning in those with Down syndrome,” said Alberto Costa, MD, Ph.D., an associate professor of medicine and the neuroscientist leading the effort.

“We have been studying this drug for three years and are now ready to analyze the data on our trial. Our team at the University of Colorado and Children’s Hospital Colorado expects to have the results in the next two or three months.”

Costa, whose work was chronicled in last Sunday’s New York Times Magazine, (A Drug for Down Syndrome), is tested the drug memantine, currently used to relieve symptoms of Alzheimer’s disease, in 39 people with Down syndrome. About half received the drug and the others a placebo. In 2007, Costa demonstrated that memantine could improve memory function in mice with Down syndrome.

And now, for the first time, he is taking a drug effective in the treatment of learning and memory deficits in mice with Down syndrome and applying it to humans, a move described by the New York Times as “a milestone in the history of Down syndrome research.”

Costa is no disinterested researcher, his 16-year-old daughter Tyche – named for the Greek goddess of Fortune - has Down syndrome. Like others with the condition, she faces the specter of a steady decline in mental functioning as she gets older and a roughly 20 percent chance of getting Alzheimer’s in her 50’s. After that diagnosis, death is often just five years away.

“I feel I am racing the clock to find something that will at least keep her functioning at the level she is at now,” Costa said. “As they age, parts of their brain will shrink and their functions will diminish.”

Costa is actively pursuing links between Down and Alzheimer’s disease. He says babies born with Down often carry the biological markers for Alzheimer’s.

“They have the disease from the get go,” he said.

Costa says the world is awash in false assumptions about Down syndrome ranging from distortions on life expectancy to educational limitations. In fact, depending on the severity of their condition, those with Down can live into their 70s, attend college, live independently and hold down jobs.

 

“If we are successful, it will increase hope and expectations for those with Down syndrome,” Costa said. “Right now there are drugs for the signs and symptoms of medical conditions more frequent in those with Down syndrome, but nothing to improve brain function. In fact, the prevailing wisdom has been that there is essentially nothing you can do to boost memory and learning in this group. Hopefully, we can prove them wrong.”

But he and other Down researchers face an overall lack of federal funding, especially when compared to other diseases and disorders.

Costa has been supported by Forest Pharmaceuticals which is funding the clinical trial, the Linda Crnic Institute for Down Syndrome, the Coleman Institute for Cognitive Disabilities at the University of Colorado and the National Institute of Child Health and Development, part of the National Institutes of Health.

“Clearly these funding sources are the unsung heroes,” Costa said. “They may not get the attention or publicity but I can assure you that our efforts and the future of those with Down syndrome would be seriously compromised without their continued generosity.”

Down Syndrome, Sleep Problems Linked

from azpm.org:

Research under way at the University of Arizona is revealing a connection between quality of sleep and the learning and memory functions in children with Down Syndrome.

"It's well known that children with Down Syndrome are vulnerable to developing sleep apnea which results in pauses in breathing," UA psychology student Jennifer Breslin says. Breslin has been conducting a study looking at children with Down Syndrome and the occurrence of sleep apnea.

"if we can demonstrate that kids with poor sleep have poor cognitive outcomes, we can make a case for intervention and ultimately improving their behavior and learning ability," she says. "If we could give these kids a better quality of life, that would be awesome."

Cognitive Development and Down Syndrome: Age-Related Change

from aaiddjournals.org:

Cognitive Development and Down Syndrome: Age-Related Change on the Stanford-Binet Test (Fourth Edition)

A study in the May issue of the American Journal on Intellectual and Developmental Disabilities by researchers affiliated with the University of Queensland (Australia) examined Stanford-Binet test performance by a large group of individuals with Down syndrome.  Authors report that the performance of the study sample on Stanford-Binet subtests measuring crystallized abilities (the ability to use skills, knowledge, and experience)  tended to plateau early in adulthood, whereas the test of fluid ability (the capacity to think logically and solve problems in novel situations, independent of acquired knowledge) continued to increase beyond the age of 30.  Authors note that the trend they observed is in opposition to the general population in which fluid abilities typically peak in early adulthood while crystallized abilities continue to increase. (full text available at no cost with member subscription to AJIDD)

Growth models for subtests of the Stanford-Binet Intelligence Scale, 4th edition (R. L. Thorndike, E. P. Hagen, & J. M. Sattler, 1986a, 1986b) were developed for individuals with Down syndrome. Models were based on the assessments of 208 individuals who participated in longitudinal and cross-sectional research between 1987 and 2004. Variation in performance among individuals was large and significant across all subtests except Memory for Sentences. Scores on the Memory for Sentences subtest remained low between ages 4 to 30 years. Greatest variation was found on the Pattern Analysis subtest, where scores continued to rise into adulthood. Turning points for scores on the Vocabulary and Comprehension subtests appeared premature relative to normative patterns of development. The authors discuss development at the subdomain level and analyze both individual and group trajectories.