Proteins are the compounds that are responsible for balancing and regulating all of the intricate chemical reactions that coordinate the biochemistry that goes on non-stop in each cell of the body. They are long strings, like links in a chain, of building blocks called amino acids hooked end to end. To become activated they must first be wrapped into a precise three dimensional structure. This brings together the functional components of the long protein molecule that bind specific compounds, place them together in an appropriate configuration, and manipulate chemical reactions. As cells age, these proteins lose their distinctive configurations. When this happens, other proteins unwind and then rewind around, or recycle, each of the functional proteins.

As part of the cellular repair and maintenance process, these repair proteins work like the recycling arm of the waste management company. They wrap around the misfolded proteins and enable them to be reconfigured in a functional fashion. The effective action of this system keeps cells young. When it goes awry, parameters of aging are accelerated.

Researchers at the University of Pennsylvania School of Medicine investigated this unfolding protein response (UPR) in sleep-deprived young and old mice. When nerve cells in the cerebral cortex were evaluated after a period of sleep deprivation, the UPR was appropriately active in the younger group but it failed to do its job in the older group. As a result, misfolded proteins built up within the cells. In addition, protein synthesis, rather than being down regulated, continued unabated thus complicating the situation. In addition, old sleep-deprived mice had more "cell death" proteins accumulate as well.

Thus, several protective neuronal mechanisms were found to be upset by sleep deprivation in the old mice. The first author of the paper that appeared in the June, 2008 issue of the Journal of Neuroscience, Nirinjini Naidoo, speculated that sleep disturbances in older humans might place an additional burden on an already stressed protein folding and degradation system. He suggested that future studies should examine whether interventions that augment key protective proteins will delay the effects of aging and reduce sleep disturbances.

Cognitive Training Studies for ADHD Yield Promising Findings

-- By Dr. David Rabiner

Although medication treatment is effective for many children with ADHD, there remains an important need to explore and develop interventions that can complement or even substitute for medication. This is true for a variety of reasons including:

1) Not all individuals with ADHD benefit from medication.
2) Among those who benefit, many have residual difficulties that need to be addressed via other means.
3) Some individuals experience adverse effects that prevent them from remaining on medication.
4) Medication treatment does not result in benefits that extend beyond when medication is being taken.

Except for #3 above, the same limitations hold for behavior therapy, which is the other intervention for ADHD that is widely considered to have a strong evidence base at this time.

Because of these limitations, some researchers have pursued cognitive training as an alternative method of treatment. The basic idea behind cognitive training is that important cognitive skills such as attention and working memory can - like any other skill - be strengthened and enhanced with intensive and focused practice. Furthermore, when an individual builds these skills the benefits may endure beyond the time when the actual training is provided.

Although this is a logical and compelling idea, the research base as it applies to individuals with ADHD is rather limited and the idea that attention is a skill that could be strengthened by focused training has not been carefully studied. In fact, when I was preparing a grant application several years ago for an attention training study, I was surprised to locate fewer than 5 studies of this issue. Furthermore, these were generally small preliminary studies that would be considered pilot investigations.

In recent years, however, researchers in the ADHD field have devoted greater attention to examining the potential benefits of cognitive training for ADHD. Below, I review 2 recent studies that highlight the potential value of training oriented approaches.

- Study 1: Computerized Progressive Attentional Training for Children with ADHD -

This study was conducted with 36 6-13-year-old children in Israel who were diagnosed with ADHD. Results from this study were published last year in Child Neurospsychology [Shalev, Tsal, & Mevorach (2007). Computerized progressive attentional training: Effective direct intervention for children with ADHD. Child Neuropsychology, 13, 382-388.]

Participants were randomly assigned to receive 8 weeks of computerized attention training (one hour sessions two times per week) or to a control group. The basic premise of computerized attention training is simple: the program requires children to attend to a variety of computer exercises and to make different responses depending on the stimuli presented. For example, a particularly simple task would require the child to press the space bar each time the number 2 was flashed but to refrain from responding when any other number is flashed. To perform well, the child must sustain their attention and refrain from responding impulsively.

Although other tasks may be far more complicated, and place demands on both problem solving skills and working memory, all tasks require sustained attention to do well. They also become more difficult and longer as the child moves through the training program. Thus, the child receives repeated practice in sustaining attention to increasingly challenging tasks that last for longer time periods. Ideally, the difficulty level adjusts to match the child's ongoing performance so that the child is constantly challenged to perform at their best possible level - not too easy but not too hard.

By succeeding in the program, the child is demonstrating an increasing ability to sustain their attention to challenging cognitive activities. Although children may get better at attending to the actual computer exercises, however, the important question is whether this generalizes to the classroom and other settings where focused attention is critical for success. If not, become better at attending to the attention training exercises would be of little value.

The attention training program tested in this study was designed to train 4 different aspects of attention: sustained attention (the ability to maintain attention and persist on task until completion), selective attention (the ability to maintain a specific cognitive set in the face of competing distractions), orienting attention (directing one's attention to critical stimuli), and executive attention (allocating attentional resources between competing demands and choosing what to attend to). During each session children were trained on these different types of attention and the tasks become more difficult as children's performance improved.

Children in the control group played computer games - rather then receiving attention training - for the same amount of time. These games also required children to sustain their attention to succeed and became more difficult as children progressed. Thus, the amount of time children spent under adult supervision working on computer activities that became more difficult as they progressed was the same for each group. Unlike children randomly assigned to the attention training group, however, children in the video game control condition were not exposed to activities that focused on training specific components of attention.

Before and immediately following training, parents rated their child's ADHD symptoms using a standardized behavior rating scale (the authors report that parents were blind to which group their child was in). In addition, academic performance was tested pre- and post-training using math problems, reading comprehension problems, and passage copying problems taken directly from children's school books. Standard achievement tests were not used because such tests are not available in Hebrew. Information about whether any children were on medication during the training or during testing was not provided.

- Results -

Encouraging results were obtained. Parents of children in the attention training group reported a significant decline in their child's inattentive symptoms compared to parents of children in the control group. The change in hyperactive-impulsive symptoms was in the same direction but was not significant.

After controlling for academic performance before training, children who received attention training did significantly better than controls in reading comprehension and in their speed of copying passages. Math performance was in the same direction but was not significant.

- Summary and Implications -

The authors conclude that their attention training program produced significant improvements in parents' ratings of inattentive symptoms and on academic tests. This is the first demonstration I am aware of that suggests attention training may improve academic performance.

The authors note several important limitations to their study. First, the sample is relatively small. Second, no behavioral data was obtained from children's teachers. Third, there was no extended follow-up so the duration of the benefits observed at post-test is unknown. To these concerns I would add that the academic results would be stronger if a standardized achievement measure had been used. Finally, I wonder if parents truly remained blind to whether their child was receiving attention training or was in the video game control group.

These limitations not withstanding, these are promising results that highlight the potential of attention training procedures for children with ADHD. A larger controlled trial that addresses the limitations of the current work is certainly warranted.

Note - To my knowledge, this attention training program is not currently available outside of Israel.

- Study 2: The impact of different types of working memory training for children with ADHD -

Working memory is a key cognitive function that allows individuals to hold information in mind for brief periods of time. This ability plays an important role in countless daily tasks including following directions, accurately tracking conversations, reading comprehension, solving complex math problems, and staying focused on a project. Current theories of ADHD that emphasize the critical role of executive functions highlight working memory deficits as an important aspect of the disorder; in fact, research has shown that many individuals with ADHD have poor working memory compared to same age peers without the disorder.

A study published several years ago reported evidence that working memory is a skill that can be improved with intensive training. In a randomized controlled trial conducted with 53 children diagnosed with ADHD, working memory training was found to yield significant gains in non-trained working memory tasks and a reduction in ADHD symptoms as reported by parents (you can find a review of this study Here). Additional controlled studies of working memory training have reported positive results in other groups including younger and older adults without ADHD, typically developing preschoolers, and stroke victims. Until recently, however, additional controlled studies documenting positive effects in children with ADHD have not been reported.

At the May 2008 recent meeting of the American Psychiatric Association, Dr. Christopher Lucas and his colleagues at NYU Medical School presented new data on the use of working memory training in children diagnosed with ADHD. Their study reported on the results of 2 different types of working memory training - auditory training or visual-spatial training - conducted with 46 children aged 7-12 who were participating in an intensive summer treatment program for ADHD.

Participants were randomly assigned to received either auditory or visual spatial working memory training using the computerized training program developed by Cogmed. The idea behind assigning children to these different types of training was to see whether one was more effective then the other; the researchers had hypothesized that children who received visual-spatial training would achieve better results.

A typical auditory training exercise would involve the computer presenting the child with a string of digits, and the child had to subsequently indicate the correct order - either forward or backward - via the keyboard. In a typical visual spatial working memory training task, the child would be required to recall the location of different objects that lit up on the screen. You can view actual examples of the working memory training tasks Here.

Training took place for 30-35 minutes per day, 4 days per week, over a 6-week period so that a target of 25 training days could be provided. Both auditory and visual-spatial training protocols automatically increased the difficulty level of the working memory tasks depending on how well the child is performing, becoming more difficult when the child is successful and easier when the child is struggling. These adjustments are made on nearly a trial by trial basis by increasing or decreasing the number of items to recall. As a result, the child is consistently challenged to work at their maximum performance level without the task becoming so difficult that they become frustrated and give up.

The researchers were interested in 2 basic questions. First, did children who received visual-spatial training show greater gains in working memory performance on non-trained tasks than children who received the auditory working memory training? This was assessed by having children complete a comprehensive working memory assessment before and after training using tasks that differed from what they were actually trained with. It is important to evaluate training using tasks that differ from training activities to see whether training improvements extend to non-trained activities.

The second question was whether visual-spatial working memory training was also associated with behavioral improvements. To answer this question, the researchers examined the number of positive behavior points, i.e., points awarded for behaving appropriately and following camp rules, that children in both groups received from camp counselors between weeks 4 and 6 of the training. The counselors who awarded points were not aware of which training condition children had been assigned to.

This represents a stringent test of working memory training on behavior for several reasons. First, the ratings were being made by blind observers. Second, most children were being treated with medication, and their behavior would already have improved because of this. Third, all children were involved in an intensive behavioral therapy program designed to promote positive behavior. Thus, any improvement from working memory training would be above and beyond gains achieved from treatments that were already in place.

- Results -

Before and after the training, children were tested on several non-trained measures of working memory. Consistent with the researchers' prediction, children who received visual-spatial training performed significantly better on several of these tasks than children who received auditory working memory training.

Of particular interest is that children who received visual-spatial working memory training earned significantly more positive behavior points from the camp counselors. Thus, these children were rated as doing a better job of consistently following camp rules and behaving appropriately.

- Summary and Implications -

Results from this study support the benefits of working memory training for children with ADHD and indicate that training of visual-spatial working memory is especially important. The fact that this training was associated with an increase in positive behavior above and beyond medication and behavior treatments already in place is a very encouraging result.

As with Study 1, this study has several limitations to consider. Although the behavior improvements noted by camp counselors is important, it would also be important to document that such behavioral gains were also observed by parents and teachers. This, however, was not examined in the study. As with Study 1, there was no extended follow-up so the duration of training benefits can not be determined.

- Overall Summary -

Results from these two cognitive training studies highlight that cognitive training interventions may provide an important complement to traditional medication treatment and behavior therapy. Both studies included appropriate control groups, employed random assignment, and had outcome measures provided by individuals who were "blind" to which condition children were assigned to. They are thus well-designed studies from which scientifically sound conclusions can be drawn. They add to the growing research base that intensive practice and training focused of key cognitive skills can have positive effects that extend beyond the training situation itself.

As noted above, however, each study has limitations that should be addressed in subsequent work. It is encouraging to see the momentum for such work building and I look forward to reviewing other studies in this important area as they become available.

 

Can We Play?

-- By Dr. David Elkind

Play is rapidly disappearing from our homes, our schools, and our neighborhoods. Over the last two decades alone, children have lost eight hours of free, unstructured, and spontaneous play a week. More than 30,000 schools in the United States have eliminated recess to make more time for academics. From 1997 to 2003, children's time spent outdoors fell 50 percent, according to a study by Sandra Hofferth at the University of Maryland. Hofferth has also found that the amount of time children spend in organized sports has doubled, and the number of minutes children devote each week to passive leisure, not including watching television, has increased from 30 minutes to more than three hours. It is no surprise, then, that childhood obesity is now considered an epidemic.

But the problem goes well beyond obesity. Decades of research has shown that play is crucial to physical, intellectual, and social-emotional development at all ages. This is especially true of the purest form of play: the unstructured, self-motivated, imaginative, independent kind, where children initiate their own games and even invent their own rules.

In infancy and early childhood, play is the activity through which children learn to recognize colors and shapes, tastes and sounds—the very building blocks of reality. Play also provides pathways to love and social connection. Elementary school children use play to learn mutual respect, friendship, cooperation, and competition. For adolescents, play is a means of exploring possible identities, as well as a way to blow off steam and stay fit. Even adults have the potential to unite play, love, and work, attaining the dynamic, joyful state that psychologist Mihaly Csikszentmihalyi calls "flow."

With play on the decline, we risk losing these and many other benefits. For too long, we have treated play as a luxury that kids, as well as adults, could do without. But the time has come for us to recognize why play is worth defending: It is essential to leading a happy and healthy life.

Play and development

Years of research has confirmed the value of play. In early childhood, play helps children develop skills they can not get in any other way. Babbling, for example, is a self-initiated form of play through which infants create the sounds they need to learn the language of their parents. Likewise, children teach themselves to crawl, stand, and walk through repetitious practice play. At the preschool level, children engage in dramatic play and learn who is a leader, who is a follower, who is outgoing, who is shy. They also learn to negotiate their own conflicts.

A 2007 report from the American Academy of Pediatrics documents that play promotes not only behavioral development but brain growth as well. The University of North Carolina's Abecedarian Early Child Intervention program found that children who received an enriched, play-oriented parenting and early childhood program had significantly higher IQ's at age five than did a comparable group of children who were not in the program (105 vs. 85 points).

A large body of research evidence also supports the value and importance of particular types of play. For example, Israeli psychologist Sara Smilansky's classic studies of sociodramatic play, where two or more children participate in shared make believe, demonstrate the value of this play for academic, social, and emotional learning. "Sociodramatic play activates resources that stimulate social and intellectual growth in the child, which in turn affects the child's success in school," concludes Smilansky in a 1990 study that compared American and Israeli children. "For example, problem solving in most school subjects requires a great deal of make believe, visualizing how the Eskimos live, reading stories, imagining a story and writing it down, solving arithmetic problems, and determining what will come next."

Other research illustrates the importance of physical play for children's learning and development. Some of these studies have highlighted the importance of recess. Psychologist Anthony Pellegrini and his colleagues have found that elementary school children become increasingly inattentive in class when recess is delayed. Similarly, studies conducted in French and Canadian elementary schools over a period of four years found that regular physical activity had positive effects on academic performance. Spending one third of the school day in physical education, art, and music improved not only physical fitness, but attitudes toward learning and test scores. These findings echo those from one analysis of 200 studies on the effects of exercise on cognitive functioning, which also suggests that physical activity promotes learning.

In recent years, and most especially since the 2002 passage of the No Child Left Behind Act, we've seen educators, policy makers, and many parents embrace the idea that early academics leads to greater success in life. Yet several studies by Kathy Hirsch-Pasek and colleagues have compared the performance of children attending academic preschools with those attending play-oriented preschools. The results showed no advantage in reading and math achievement for children attending the academic preschools. But there was evidence that those children had higher levels of test anxiety, were less creative, and had more negative attitudes toward school than did the children attending the play preschools.

So if play is that important, why is it disappearing?

The perfect storm

The decline of children's free, self-initiated play is the result of a perfect storm of technological innovation, rapid social change, and economic globalization.

Technological innovations have led to the all-pervasiveness of television and computer screens in our society in general, and in our homes in particular. An unintended consequence of this invasion is that childhood has moved indoors. Children who might once have enjoyed a pick-up game of baseball in an empty lot now watch the game on TV, sitting on their couch.

Meanwhile, single and working parents now outnumber the once-predominant nuclear family, in which a stay-at-home mother could provide the kind of loose oversight that facilitates free play. Instead, busy working parents outsource at least some of their former responsibilities to coaches, tutors, trainers, martial arts teachers, and other professionals. As a result, middle-income children spend more of their free time in adult-led and -organized activities than any earlier generation. (Low-income youth sometimes have the opposite problem: Their parents may not have the means to put them in high-quality programs that provide alternatives to playing in unsafe neighborhoods.)

Finally, a global economy has increased parental fears about their children's prospects in an increasingly high-tech marketplace. Many middle-class parents have bought into the idea that education is a race, and that the earlier you start your child in academics, the better. Preschool tutoring in math and programs such as the Kumon System, which emphasizes daily drills in math and reading, are becoming increasingly popular. And all too many kindergartens, once dedicated to learning through play, have become full-day academic institutions that require testing and homework. In such a world, play has come to be seen as a waste of precious time. A 1999 survey found that nearly a third of kindergarten classes did not have a recess period.

As adults have increasingly thwarted self-initiated play and games, we have lost important markers of the stages in a child's development. In the absence of such markers, it is difficult to determine what is appropriate and not appropriate for children. We run the risk of pushing them into certain activities before they are ready, or stunting the development of important intellectual, social, or emotional skills.

For example, it is only after the age of six or seven that children will spontaneously participate in games with rules, because it is only at that age that they are fully able to understand and follow rules. Those kinds of developmental markers fall by the wayside when we slot very young kids into activities such as Little League. When Little League was founded in 1939, the adult organizers looked to children themselves in setting the starting age, which ended up being about age nine or older. But the success of Little League was not lost on parents eager to find supervised activities for young children. Before long, team soccer was promoted for younger children because it was an easier and less complex game for the six- to nine-year-old age group. The rapid growth of soccer leagues challenged the popularity of Little League. This led to the introduction of Tee Ball, a simplified version of baseball for children as young as four.

By pushing young children into team sports for which they are not developmentally ready, we rule out forms of play that once encouraged them to learn skills of independence and creativity. Instead of learning on their own in backyards, fields, and on sidewalks, children are only learning to do what adults tell them to do. Moreover, one study found that many children who start playing soccer at age four are burned out on that sport by the time they reach adolescence, just the age when they might truly enjoy and excel at it.

Bring back play

Play is motivated by pleasure. It is instinctive and part of the maturational process. We cannot prevent children from self-initiated play; they will engage in it whenever they can. The problem is that we have curtailed the time and opportunities for such play. Obviously we cannot turn the clock back and reverse the technological, social, and economic changes that have helped silence children's play. Television, computers, new family models, and globalization are here to stay.

What is important is balance. If a child spends an hour on the computer or watching TV, equal time should be given to playing with peers or engaging in individual activities like reading or crafts. It is important to involve the child in making these decisions and setting the parameters for how they spend their time. If we give children some ownership of the rules, they are usually more willing to follow them than when they are simply imposed from above. It is also important to appreciate individual differences. You will not be able to keep some children from playing sports, while others prefer more sedentary activities.

Another way we can help bring play back into children's lives is to have schools restore recess for at least half an hour. As research demonstrates, academics are unlikely to suffer from this change; if anything, they'll benefit. Schools also argue that they cannot afford recess because of high insurance costs and parents' greater appetite for litigation. But when I speak with insurance officers about this issue, they claim that argument is overblown. Either way, children could still be taken outside, or to the gym, for calisthenics to exercise their bodies.

We must also address the more general problem of test-driven curricula in today's schools. When teachers are forced to teach to the test, they become less innovative in their teaching methods, with less room for games and imagination. More creative teaching methods build upon children's interests and attitudes—their playful disposition—and this encourages them to enjoy their teachers, which in turn enhances their interest in the subject matter. Though computers are one of the forces limiting play, they can be creatively used in the service of playful learning. As more young teachers who are proficient in technology enter the schools, we will have the first true educational reform in decades, if not centuries.

But you don't have to be a teacher to help bring back play. Many neighborhoods badly need more playgrounds. This was also the case in the 1930s; in response, we saw the "playground movement," when local communities set up their own playgrounds. A new playground movement is long overdue, especially for our inner city neighborhoods, where safe play spaces are often in short supply. A playground should be required of any new large-scale housing development.

We could go further. In Scandinavian countries, there are play areas in even the best restaurants, as well as in airports and train stations. These countries appreciate the importance of play for healthy development, and we could well follow their example.

Finally children do as we do, not as we say. That gives us incentive to bring play back into our adult lives. We can shut off the TVs and take our children with us on outdoor adventures. We should get less exercise in the gym and more on hiking trails and basketball courts. We can also make work more playful: Businesses that do this are among the most successful. Seattle's Pike Fish Market is a case in point. Workers throw fish to one another, engage the customers in repartee, and appear to have a grand time. Some companies, such as Google, have made play an important part of their corporate culture. Study after study has shown that when workers enjoy what they do and are well-rewarded and recognized for their contributions, they like and respect their employers and produce higher quality work. For example, when the Rohm and Hass Chemical company in Kentucky reorganized its workplace into self-regulating and self-rewarding teams, one study found that worker grievances and turnover declined, while plant safety and productivity improved.

When we adults unite play, love, and work in our lives, we set an example that our children can follow. That just might be the best way to bring play back into the lives of our children—and build a more playful culture.

 

Autistic Spectrum Disorders (ASDs) are neurodevelopmental disorders that have much better outcomes the earlier they are diagnosed.and the sooner children are enrolled in appropriate intervention programs. To help disseminate information to more effectively avoid a delayed diagnosis it important to make available some of the earliest signs and symptoms to watch for.

The Child Neurology Service "red flags" screening parameters include the following as absolute indications for immediate evaluation for autism:

1) no babbling or pointing or other gesturing by 12 months of age

2) no single words by 16 months

3) no spontaneous 2-word phrases by 24 months

4) loss of language or social skills at any age

Speech delays usually prompt parents to raise concerns with their child's pediatrician at 16 to 19 months. However, certain social deficits occur earlier and may be more specific but more difficult to recognize. Presenting symptoms can vary widely from one child to the next. Some may be perceived by parents as just "being different" during the first few months of life. Inability to manifest social relatedness by developing connections with others and sharing complementary states is common. These children are content being alone, ignore their parents bids for attention, and seldom make eye contact or bid for other's attention with gestures or vocalizations.

Difficulty with skills such as joint activity is a distinguishing characteristic of very young children with autism. Joint activity refers to the behavior whereby the infant shows enjoyment in sharing an object or an experience with another person by looking back and forth between the two. Early in life it frequently appears as joyous smiling in recognition of a parent's attention or vocalization. At about 8 months of age, an infant starts to follow a parent's gaze and look in the same direction. At 10-12 months children begin to look in the same direction when a parent points at an interesting object. This is usually accompanied by the child looking back at the parent as if to acknowledge a shared appreciation. At 12 to 14 months children typically begin to initiate pointing themselves usually to request a desired object and then to draw the parent's attention to share an interesting object. These pointing episodes are frequently accompanied with a back and forth gaze of the child between the object and the parent in effect to "share" the experience. Orienting to social stimuli such as turning consistently to respond to one's name is an early (8-10 months) trait that is often deficient.

Most children later diagnosed with autism are sent to their doctor for "speech delay." Most parents sense that something is wrong by 18-20 months. Earlier pre-speech deficits often exist and should be looked for. These traits include:

1) lack of appropriate gaze

2) lack of warm, joyful expressions

3) lack of the alternating to-and-fro pattern of vocalizations between infant and parent that usually occurs at approximately 6 months of age (ie, infants with autistic tendencies usually continue vocalizing without regard for the parent's speech)

4) lack of recognition of parent's voice

5) disregard for vocalizations such as calling of the child's name but with preserved awareness of environmental sounds

6) delayed onset of babbling past 9 months

7) decreased use of pre-speech gestures such as  waving or pointing

8) lack of expressions such as "oh oh" or "huh"

9) Lack of interest or response of any kind to neutral statements such as "Oh no, it's raining again!"

If you see these changes, please suggest that the child be evaluated as soon as possible because an early, proper diagnosis means starting treatment at a time when the intervention is likely to result in a better outcome for the child.

 

 

The association between smoking and cognitive function (thinking, learning and memory) has been discussed extensively in recent years. The consensus has been that smoking negatively impacts brain function. However, evaluating this effect in older persons is problematic because old smokers frequently die or don't return for follow-up assessments. One way to avoid some of these problems in clinical study design is to explore the association between smoking and cognitive function before dementia develops.

The link between mild cognitive impairment and dementia is well established. Therefore, it is logical to determine whether there is an association between smoking  and cognitive impairment in midlife. Evidence of a link at younger ages would bolster the contention that smoking is involved in the production of cognitive decline.

Data in a recent study were drawn from 10,308 civil servants in the UK who were followed for an average of 17 years. The relationship between smoking history and multiple domains of cognition was investigated sequentially in middle-aged individuals aged 35-55 at baseline. They included memory, reasoning, vocabulary, and semantic and phonemic fluency.

Compared to those who had never smoked, middle-aged smokers experienced memory deficits and declines in reasoning abilities. Compared with smokers, long-term ex-smokers were less likely to have cognitive problems in memory, vocabulary and verbal fluency. The study also documented that those who gave up smoking in midlife manifested improvements in other health related behaviors such as diet and activity.

These results are significant because individuals with cognitive impairment in midlife due to smoking may progress to dementia at a more rapid rate.

 

 

ScienceDaily (June 11, 2008) — A 115-year-old woman who remained mentally alert throughout her life had an essentially normal brain, with little or no evidence of Alzheimer's disease, according to a study in the August issue of Neurobiology of Aging.

The findings question the assumption that Alzheimer's disease or other forms of dementia will inevitably develop, if people live long enough. "Our observations suggest that, in contrast to general belief, the limits of human cognitive function may extend far beyond the range that is currently enjoyed by most individuals, and that improvements in preventing brain disorders of aging may yield substantial long-term benefits," according to a study led by Prof. dr. Gert Holstege of University Medical Centre Groningen, The Netherlands.

Dr. Holstege and colleagues had a unique chance to test the mental functioning of one of the world's oldest humans, and then to compare their findings with the condition of the subject's brain after death. The patient was a Dutch woman who, at age 82, made arrangements to donate her body to science after death. At age 111, she contacted the researchers to ask whether her body would still be useful for research or teaching purposes. They assured her that, contrary to what she thought, they were especially interested because of her age: "She was very enthusiastic about her being important for science," Dr. Gert Holstege and colleagues write.

The researchers found the patient to be "an alert and assertive lady, full of interest in the world around her, including national and international politics and sports." She had lived independently until moving to a residential care home at age 105, mainly because of poor eyesight. Ironically, she had been very small at birth and was not expected to survive.

A series of neurological and psychological examinations were performed when the patient was 112 and 113 years old. The results were essentially normal, with no signs of dementia or problems with memory or attention. In general, her mental performance was above average for adults aged 60 to 75.

As planned, her body was donated to science when she died at age 115. At the time, she was the world's oldest woman. Examination after death found almost no evidence of atherosclerosis (narrowing of the arteries) anywhere in her body. The brain also showed very few abnormalities--the number of brain cells was similar to that expected in healthy people between 60 and 80 years old.

A key finding was the absence of brain abnormalities typical of Alzheimer's disease. There were almost no deposits of a substance called beta-amyloid, which are characteristic of Alzheimer's patients. The other abnormalities present, including "neurofibrillary tangles," were very mild--too early to cause significant mental impairment.

The unique case lends new insights into the potential for preserving brain function in very elderly patients. Previous studies have found at least mild abnormalities in the brains of nearly all "cognitively normal" elderly people. As the number of people living to age 100 and beyond continues to increase, the findings suggest that deterioration of the brain is not inevitable.

 

 

Increasing rates of obesity have led to concerns about an epidemic of adverse health consequences. Obesity is most simply characterized by measuring waist circumference or waist to hip ratio (WHR). The frequent association of abdominal obesity, as determined by the WHR, with elevation of serum triglycerides, decline in HDL (the "good cholesterol"), hypertension and diabetes constitute a metabolic constellation often referred to as Syndrome X, or the Metabolic Syndrome. It is an important risk factor for cardiovascular disease and stroke.

Obesity has been linked to the development of Alzheimer disease and specific changes in brain structure. Based on the correlation between obesity, dementia and cardio-metabolic factors, investigations have focused on defining potential alterations in brain anatomy seen in this context. Magnetic Resonance Imaging (MRI) was chosen as the desired imaging modality because of its capacity for high spatial resolution and quantitative assessment.

MRI measures that have been previously linked to cognitive impairment and dementia include  hippocampal volume (HV) and white matter hyperintensities (WMH). The hippocampus is a region of the brain essential for memory processing and retrieval. Cerebral white matter consists of nerve cell processes that serve to connect distant clusters of neurons into functional networks. Decreases in HV and and increases in WMH have been shown to contribute independently to the risk of dementia. Because WHR is a component of the Metabolic Syndrome, associations between it and these structural brain changes were investigated.

A recent study was conducted in the Central Valley of California including 112 individuals in the Latino community. WHR determinations, MRI scans and metabolic assessments were performed.  In this cross-sectional analysis greater WHR was associated with a fall in HV and an increase in WMH. A one standard deviation increase in WHR was associated with a 27% increase in WMH. It is important to note that these relationships were not affected by adjustment for body mass index (BMI) (a measure of generalized obesity), total cholesterol level, fasting blood glucose, serum insulin levels or systolic blood pressure.

Although prior studies have shown correlations between HV and WMH with various metabolic and cardiovascular factors, in this study they did not explain the entire association. The authors suggested other potential etiologies such as inflammatory mechanisms linked to the central fat depots, stress and elevation of the stress hormone cortisol as additional factors.

These findings complement a large body of data that demonstrate the negative effects of obesity on cognitive function. They are also consistent with the emerging reports of the beneficial effects of exercise on cognition. One result of exercise may be improved weight regulation. Taken together, these findings provide further support for the suggestion that structural brain changes might be at least partially modifiable by lifestyle alterations.

The only drug approved by the FDA for the acute treatment of strokes is tPA. tPA is the "clot busting" drug that must be given very shortly after a stroke has started. It's major side effect is bleeding which may occur in the brain. If this happens, additional damage to the brain can occur. Because of the short time window during which it may be administered, many people don't get to the hospital soon enough to qualify for use of tPA.

A novel new function may breathe new life into an old drug. Minocycline, an antibiotic used to treat acne, may be an alternative treatment for stroke. It is a semisynthetic cousin of tetracycline. It has been shown to have neuroprotective effects in animal models of multiple sclerosis (MS), Parkinson disease, Huntington disease and ALS (Lou Gehrig's disease). The mechanisms responsible for the death of nerve cells in these diseases share many similarities with cell death pathways in stroke. This prompted investigators to evaluate minocycline in a rodent stroke model. Pyramidal neuron (a type of nerve cell) survival increased from 10 to 77% after administration of minocycline. In another animal stroke model, even when administered 48 hours after a stroke developed, minocycline reduced the size of the stroke.

The proposed mechanisms of minocycline's actions appear to have nothing to do with its antibiotic effects. It seems to have significant anti-inflammatory activities as well as a novel ability to inhibit what are referred to as cell death cascades (that cause nerve cells to essentially self destruct under adverse circumstances) triggered by stroke-like events.

In an open-label, evaluator-blinded study done at Edith Wolfson Hospital in Holon, Israel, minocycline was given to stroke patients for five days. It was started between 6 and 24 hours after onset of a stroke. One hundred fifty-one patients were enrolled in the study. They were followed for 90 days. Recovery rate and final neurological status were evaluated. Improvement was noted as early as day 7. No evidence of recurrent stroke or hemorrhage was noted during the follow-up period. Patients had significantly improved outcome with minocycline treatment in this open label study.

It appears that the beneficial actions of minocycline, especially its antagonism of cell death pathways, which are not engaged acutely during a stroke, make it a potentially useful candidate for stroke therapy with a wider therapeutic time window. Based on these promising preliminary findings, Dr. David Hess at the Medical College of Georgia will further study the efficacy of minocycline in acute stroke in a prospective double-blinded human trial. The current focus of the study is to determine drug safety, optimal dosing regimens and during of therapy.

If previous findings are upheld, minocycline may become a new "standard" therapy for patients experiencing symptoms of acute stroke.

 

The purpose of sleep is unknown. What is known is that it not only occurs in humans, but all mammals, and even as far back as box jelly fish and species such as the fruit fly Drosophila melanogaster. This suggests that sleep-like states are evolutionarily ancient. Now evidence suggests that a quiescent behavioral state exists in the nematode Caenorhabditis elegans, a round worm. This quiescent state develops during a developmental stage called lethargus, which temporally occurs before each of its four moults in larval stage transitions. 

Quiescence in C. elegans demonstrates certain specific characteristics of sleep. A key feature of sleep is reduced sensory responsiveness. This is manifested in C. elegans by decreased responses to abrupt mechanical and strident olfactory (smell) stimuli. This quiescent state is reversible, as is sleep. It also manifests a "homeostatic," or metabolically refreshing, quality when, after a period of enforced wakefulness, subsequent sleep occurs more rapidly and is deeper.

The temporal relationship between lethargus and the moult, which is essential for growth and development of the animal, is a period of enhanced biosynthetic activity. This is consistent with the sleep-like state playing a vital role in growth and development of the organism. Also related to lethargus are vital alterations in the nervous system and the connectivity between individual nerve cells. Connections between nerve cells are called synapses. The process of modification of these connections is called called plasticity. Plasticity is the basis for learning and memory and reflects what happens during the developmental stages in round worms. It is also a vital brain process in humans.

Strengthening of new neuronal connections is called consolidation and is necessary for the solidification of learning. This process requires expenditure of substantial amounts of cellular energy and must provide significant benefits. These synaptic modifications (plasticity and consolidation) associated with lethargus in C. elegans promote nervous system changes that are important in the organism's life cycle.  Such a role in nervous system development, maturation and function is notable in light of information suggesting that sleep, and sleep-like states, are necessary for the production of changes in the nervous system.

These findings highlight potential roles played by sleep in humans. It is well-known that sleep deprivation acutely diminishes mental functions. Chronic sleep deprivation is associated with elevations in the stress hormone cortisol. Cortisol, in excess, can cause shrinkage and loss of nerve cell connections (synapses). This occurs in association with aging and is more severe in dementing conditions such as Alzheimer disease. These findings are evidence of the importance of adequate sleep not only for provision of cognition, but also for the prevention of neuronal changes seen in severe memory loss states.

 

Autism is a neurodevelopmental disorder with genetic and environmental influences. It has increased dramatically in incidence over the past 25 years. A newly published study conducted by researchers at the University of Texas Health Science Center in San Antonio explored the link between industrial release of mercury and increased autism rates. Data documenting mercury release were from 39 coal-fired power plants and 56 industrial facilities in Texas. Autism rates were examined from 1,040 Texas school districts.

For every 1,000 pounds of mercury released by all industrial sources into the environment in Texas in 1998, there was a corresponding 2.6% increase in autism rates in the Texas school districts in 2002. For every 1,000 pounds of mercury released by Texas power plants in 1998, there was a corresponding 3.7% increase in autism rates in Texas school districts in 2002. The researchers found that autism prevalence is reduced by 1-2% with each 10 miles of distance from a pollution source.

The United States Environmental Protection Agency estimated annual environmental mercury releases to be 158 million tons nationwide in the late 1990s. Dr. Palmer, one of the investigators, said, "We need to be concerned about global mercury emissions since a substantial proportion of mercury releases are spread around the world by long-range air and ocean currents. Steps for controlling and eliminating mercury pollution on a worldwide basis may be advantageous."

These new findings are similar to a number of other studies that confirm the presence of higher amounts of bodily incorporation of mercury in plant species, animals and humans the closer they are to the pollution source. The authors noted, "We suspect low-dose exposures to various environmental toxicants, including mercury, that occur during critical windows of neural development among genetically susceptible children may increase the risk for developmental disorders such as autism." There is additional evidence from unrelated studies that children and other developing organisms are more susceptible to the neurobiological effects of mercury exposure.