Neuroscience

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Posts tagged aging

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Dietary Flavanols Reverse Age-Related Memory Decline

Dietary cocoa flavanols—naturally occurring bioactives found in cocoa—reversed age-related memory decline in healthy older adults, according to a study led by Columbia University Medical Center (CUMC) scientists. The study, published today in the advance online issue of Nature Neuroscience, provides the first direct evidence that one component of age-related memory decline in humans is caused by changes in a specific region of the brain and that this form of memory decline can be improved by a dietary intervention.

As people age, they typically show some decline in cognitive abilities, including learning and remembering such things as the names of new acquaintances or where they parked the car or placed their keys. This normal age-related memory decline starts in early adulthood but usually does not have any noticeable impact on quality of life until people reach their fifties or sixties. Age-related memory decline is different from the often-devastating memory impairment that occurs with Alzheimer’s, in which a disease process damages and destroys neurons in various parts of the brain, including the memory circuits.

Previous work, including by the laboratory of senior author Scott A. Small, MD, had shown that changes in a specific part of the brain—the dentate gyrus—are associated with age-related memory decline. Until now, however, the evidence in humans showed only a correlational link, not a causal one. To see if the dentate gyrus is the source of age-related memory decline in humans, Dr. Small and his colleagues tested whether compounds called cocoa flavanols can improve the function of this brain region and improve memory. Flavanols extracted from cocoa beans had previously been found to improve neuronal connections in the dentate gyrus of mice.

Dr. Small is the Boris and Rose Katz Professor of Neurology (in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, the Sergievsky Center, and the Departments of Radiology and Psychiatry) and director of the Alzheimer’s Disease Research Center in the Taub Institute at CUMC.

A cocoa flavanol-containing test drink prepared specifically for research purposes was produced by the food company Mars, Incorporated, which also partly supported the research, using a proprietary process to extract flavanols from cocoa beans. Most methods of processing cocoa remove many of the flavanols found in the raw plant.

In the CUMC study, 37 healthy volunteers, ages 50 to 69, were randomized to receive either a high-flavanol diet (900 mg of flavanols a day) or a low-flavanol diet (10 mg of flavanols a day) for three months. Brain imaging and memory tests were administered to each participant before and after the study. The brain imaging measured blood volume in the dentate gyrus, a measure of metabolism, and the memory test involved a 20-minute pattern-recognition exercise designed to evaluate a type of memory controlled by the dentate gyrus.

“When we imaged our research subjects’ brains, we found noticeable improvements in the function of the dentate gyrus in those who consumed the high-cocoa-flavanol drink,” said lead author Adam M. Brickman, PhD, associate professor of neuropsychology at the Taub Institute.

The high-flavanol group also performed significantly better on the memory test. “If a participant had the memory of a typical 60-year-old at the beginning of the study, after three months that person on average had the memory of a typical 30- or 40-year-old,” said Dr. Small. He cautioned, however, that the findings need to be replicated in a larger study—which he and his team plan to do.    

Flavanols are also found naturally in tea leaves and in certain fruits and vegetables, but the overall amounts, as well as the specific forms and mixtures, vary widely.

The precise formulation used in the CUMC study has also been shown to improve cardiovascular health. Brigham and Women’s Hospital in Boston recently announced an NIH-funded study of 18,000 men and women to see whether flavanols can help prevent heart attacks and strokes.

The researchers point out that the product used in the study is not the same as chocolate, and they caution against an increase in chocolate consumption in an attempt to gain this effect.

Two innovations by the investigators made the study possible. One was a new information-processing tool that allows the imaging data to be presented in a single three-dimensional snapshot, rather than in numerous individual slices. The tool was developed in Dr. Small’s lab by Usman A. Khan, an MD-PhD student in the lab, and Frank A. Provenzano, a biomedical engineering graduate student at Columbia. The other innovation was a modification to a classic neuropsychological test, allowing the researchers to evaluate memory function specifically localized to the dentate gyrus. The revised test was developed by Drs. Brickman and Small.

Besides flavanols, exercise has been shown in previous studies, including those of Dr. Small, to improve memory and dentate gyrus function in younger people. In the current study, the researchers were unable to assess whether exercise had an effect on memory or on dentate gyrus activity. “Since we didn’t reach the intended VO2max (maximal oxygen uptake) target,” said Dr. Small, “we couldn’t evaluate whether exercise was beneficial in this context. This is not to say that exercise is not beneficial for cognition. It may be that older people need more intense exercise to reach VO2max levels that have therapeutic effects.”

Filed under aging memory decline flavanols dentate gyrus cognition memory neuroscience science

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Genes exhibit different behaviours in different stages of development

The effect that genes have on our brain depends on our age. These are the findings of a group of researchers from the MedUni Vienna. It has been known for a number of years that particular genetic variations are of importance for the functioning of neural circuits in the brain. Just how these effects differ in the various stages of life has until recently not been fully understood. This international study has been able to demonstrate that genetic variations at different times in our lives can actually have opposite effects on the brain, which provides an explanation for the differences that clinicians observe in the psychiatric symptoms and response to medications of adolescents and adults.

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The group of researchers from Vienna, in collaboration with international cooperation partners, has shown that the effect of a psychiatric risk gene on a resting state network in the forebrain depends greatly on the patient’s age.

The human forebrain is crucial for planning and action, which are closely interwoven with concentration, attention and memory functions. The nerve transmitter substance dopamine orchestrates the activity of neurons in the forebrain in order to ensure an ideal level of functioning. The amount of dopamine in the brain is not constant for life, however. Instead, it rises until adolescence and then falls by the time the individual reaches early adulthood to a much lower level. When the dopaminergic control function collapses, serious mental illnesses such as schizophrenia, depression or attention deficit / hyperactivity disorder (ADHD) can result that usually start around the period of transition to adulthood.

For a number of years, doctors have known that a risk gene involved in dopamine metabolism (COMT) can affect neuronal regulation of the forebrain in adults. Carriers of risk gene variants are more prone to dopaminergic mental illness.

The interaction of genes and stages of development

As part of the study, carried out at the MedUni Vienna’s University Department of Psychiatry and Psychotherapy (led by Siegfried Kasper), the study team used magnetic resonance imaging data from a large random sample of over 200 test subjects to analyse the complex interaction between stages of development and genetic variations in the COMT gene and how it affects the resting state network of the forebrain.
Some of the magnetic resonance scans were performed in Vienna (Centre of Excellent, High-Field MR, Department of MR Physics, Head: Ewald Moser) and some as part of an EU project (Institute of Psychiatry, London, Head: Gunther Schumann). Gene analyses (COMT Val158Met) were carried out in Vienna (Univ. Dept. of Laboratory Medicine, Harald Esterbauer and colleagues) or as part of the EU project.

"Our age has a crucial influence on the effects of psychiatric risk genes. A gene that has positive effects during puberty can be bad for us in adulthood," says study leader Lukas Pezawas, describing the results. In the study, adolescents exhibited contrary gene effects on the brain compared to adults.

The study highlights the dynamism of gene effects on brain function throughout the various stages of life such as adolescence or adulthood. “These results are important for understanding the onset of illness in conditions such as schizophrenia, depression or ADHD, which mostly occur at the threshold of adulthood. Our results also show that there are fundamental differences in the dopamine system between adolescents and adults, which we need to take into account in future treatments”, explains Pezawas.

(Source: meduniwien.ac.at)

Filed under genes dopamine brain function cognition prefrontal cortex aging neuroscience science

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A rich vocabulary can protect against cognitive impairment
Some people suffer incipient dementia as they get older. To make up for this loss, the brain’s cognitive reserve is put to the test. Researchers from the University of Santiago de Compostela have studied what factors can help to improve this ability and they conclude that having a higher level of vocabulary is one such factor.
‘Cognitive reserve’ is the name given to the brain’s capacity to compensate for the loss of its functions. This reserve cannot be measured directly; rather, it is calculated through indicators believed to increase this capacity.
A research project at the University of Santiago de Compostela (USC) has studied how having a wide vocabulary influences cognitive reserve in the elderly.
As Cristina Lojo Seoane, from the USC, co-author of the study published in the journal ‘Anales de Psicología’(Annals of Psychology), explains to SINC: “We focused on level of vocabulary as it is considered an indicator of crystallised intelligence (the use of previously acquired intellectual skills). We aimed to deepen our understanding of its relation to cognitive reserve.”
The research team chose a sample of 326 subjects over the age of 50 – 222 healthy individuals and 104 with mild cognitive impairment. They then measured their levels of vocabulary, along with other measures such as their years of schooling, the complexity of their jobs and their reading habits.
They also analysed the scores they obtained in various tests, such as the vocabulary subtest of the ‘Wechsler Adult Intelligence Scale’(WAIS) and the Peabody Picture Vocabulary Test.
“With a regression analysis we calculated the probability of impairment to the vocabulary levels of the participants,” Lojo Seoane continues.
The results revealed a greater prevalence of mild cognitive impairment in participants who achieved a lower vocabulary level score.
“This led us to the conclusion that a higher level of vocabulary, as a measure of cognitive reserve, can protect against cognitive impairment,” the researcher concludes.

A rich vocabulary can protect against cognitive impairment

Some people suffer incipient dementia as they get older. To make up for this loss, the brain’s cognitive reserve is put to the test. Researchers from the University of Santiago de Compostela have studied what factors can help to improve this ability and they conclude that having a higher level of vocabulary is one such factor.

‘Cognitive reserve’ is the name given to the brain’s capacity to compensate for the loss of its functions. This reserve cannot be measured directly; rather, it is calculated through indicators believed to increase this capacity.

A research project at the University of Santiago de Compostela (USC) has studied how having a wide vocabulary influences cognitive reserve in the elderly.

As Cristina Lojo Seoane, from the USC, co-author of the study published in the journal ‘Anales de Psicología’(Annals of Psychology), explains to SINC: “We focused on level of vocabulary as it is considered an indicator of crystallised intelligence (the use of previously acquired intellectual skills). We aimed to deepen our understanding of its relation to cognitive reserve.”

The research team chose a sample of 326 subjects over the age of 50 – 222 healthy individuals and 104 with mild cognitive impairment. They then measured their levels of vocabulary, along with other measures such as their years of schooling, the complexity of their jobs and their reading habits.

They also analysed the scores they obtained in various tests, such as the vocabulary subtest of the ‘Wechsler Adult Intelligence Scale’(WAIS) and the Peabody Picture Vocabulary Test.

“With a regression analysis we calculated the probability of impairment to the vocabulary levels of the participants,” Lojo Seoane continues.

The results revealed a greater prevalence of mild cognitive impairment in participants who achieved a lower vocabulary level score.

“This led us to the conclusion that a higher level of vocabulary, as a measure of cognitive reserve, can protect against cognitive impairment,” the researcher concludes.

Filed under cognitive impairment cognitive reserve dementia aging vocabulary psychology neuroscience science

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Physical exercise in old age can stimulate brain fitness, but effect decreases with advancing age
Physical exercise in old age can improve brain perfusion as well as certain memory skills. This is the finding of Magdeburg neuroscientists who studied men and women aged between 60 and 77. In younger individuals regular training on a treadmill tended to improve cerebral blood flow and visual memory. However, trial participants who were older than 70 years of age tended to show no benefit of exercise. Thus, the study also indicates that the benefits of exercise may be limited by advancing age. Researchers of the German Center for Neurodegenerative Diseases (DZNE), the University of Magdeburg and the Leibniz Institute for Neurobiology have published these results in the current edition of the journal “Molecular Psychiatry”. Scientists at the Karolinska Institute in Stockholm and the Max Planck Institute for Human Development were also involved in the study.

The 40 test volunteers were healthy for their age, sedentary when the study commenced and divided into two groups. About half of the study participants exercised regularly on a treadmill for 3 months. The other individuals merely performed muscle relaxation sessions. In 7 out of 9 members of the exercise group who were not more than 70 years old, the training improved physical fitness and also tended to increase perfusion in the hippocampus – an area of the brain which is important for memory function. The increased perfusion was accompanied by improved visual memory: at the end of the study, these individuals found it easier to memorize abstract images than at the beginning of the training program. These effects were largely absent in older volunteers who participated in the workout as well as in the members of the control group.
The study included extensive tests of the volunteers’ physical condition and memory. Furthermore, the study participants were examined by magnetic resonance imaging (MRI). This technique enables detailed insights into the interior of the brain.
Exercising against dementia
Physical exercise is known to have considerable health benefits: the effects on the body have been researched extensively, the effects on brain function less so. An increase in brain perfusion through physical exercise had previously only been demonstrated empirically in younger people. The new study shows that some ageing brains also retain this ability to adapt, even though it seems to decrease with advancing age. Furthermore, the results indicate that changes in memory performance resulting from physical exercise are closely linked to changes in brain perfusion.
“Ultimately, we aim to develop measures to purposefully counteract dementia such as Alzheimer’s disease. This is why we want to understand the effects of physical exercise on the brain and the related neurobiological mechanisms. This is essential for developing treatments that are truly effective,” is how Professor Emrah Düzel, site speaker of the DZNE in Magdeburg and director of the Institute of Cognitive Neurology and Dementia Research at the University of Magdeburg, explains the background to the study.
The goal: new brain cells
The researchers’ goal is to cause new nerve cells to grow in the brain. This is how they intend to counter the loss of neurons typical of dementia. “The human brain is able to change and evolve throughout our lives. New nerve cells can form even in adult brains,” says Düzel. “Our aim is to stimulate this so-called neurogenesis. We don’t yet know whether our training methods promote the development of new brain cells. However, fundamental research shows that the formation of new brain cells often goes hand in hand with improved brain perfusion.”
Changes in the hippocampus
Indeed, it did turn out that the treadmill exercise sessions caused more blood to reach the hippocampus in younger participants. “This improves the supply of oxygen and nutrients and may also have other positive effects on the brain’s metabolism,” says the neuroscientist. “However, we have also seen that the effect of the training decreases with age. It is less effective in people aged over 70 than in people in their early 60s. It will be an important goal of our research to understand the causes for this and to find remedies.”
Düzel adds: “It is encouraging to see that visual memory improved as brain perfusion increased. However, effective treatments would also have to affect other brain functions. In our study, the effect was limited to visual short-term memory.”
A combined training for body and mind
Other experiments are now under way in Magdeburg in which test participants are sent on an unusual kind of scavenger hunt: they are assigned the task of finding objects concealed in a computer-generated landscape which is pictured on a large screen. Movement control in this virtual world is done with the help of a treadmill. “This complex situation makes high demands on motor skills and sense of orientation,” explains Düzel. “It challenges both the brain as well as the muscles.”
In the long term, the scientists aim to include people in the early stages of Alzheimer’s disease in their study program. “We are looking for ways of delaying or even stopping the progression of the disease. And we are also researching methods of prevention,” emphasizes Düzel. “Connecting physical activity and mental exercise may have a broad impact, and combined training might become a therapeutic approach. However, this has yet to be shown. In fact, our current results suggest that we may need pharmacological treatments to make exercise more effective.”

Physical exercise in old age can stimulate brain fitness, but effect decreases with advancing age

Physical exercise in old age can improve brain perfusion as well as certain memory skills. This is the finding of Magdeburg neuroscientists who studied men and women aged between 60 and 77. In younger individuals regular training on a treadmill tended to improve cerebral blood flow and visual memory. However, trial participants who were older than 70 years of age tended to show no benefit of exercise. Thus, the study also indicates that the benefits of exercise may be limited by advancing age. Researchers of the German Center for Neurodegenerative Diseases (DZNE), the University of Magdeburg and the Leibniz Institute for Neurobiology have published these results in the current edition of the journal “Molecular Psychiatry”. Scientists at the Karolinska Institute in Stockholm and the Max Planck Institute for Human Development were also involved in the study.

The 40 test volunteers were healthy for their age, sedentary when the study commenced and divided into two groups. About half of the study participants exercised regularly on a treadmill for 3 months. The other individuals merely performed muscle relaxation sessions. In 7 out of 9 members of the exercise group who were not more than 70 years old, the training improved physical fitness and also tended to increase perfusion in the hippocampus – an area of the brain which is important for memory function. The increased perfusion was accompanied by improved visual memory: at the end of the study, these individuals found it easier to memorize abstract images than at the beginning of the training program. These effects were largely absent in older volunteers who participated in the workout as well as in the members of the control group.

The study included extensive tests of the volunteers’ physical condition and memory. Furthermore, the study participants were examined by magnetic resonance imaging (MRI). This technique enables detailed insights into the interior of the brain.

Exercising against dementia

Physical exercise is known to have considerable health benefits: the effects on the body have been researched extensively, the effects on brain function less so. An increase in brain perfusion through physical exercise had previously only been demonstrated empirically in younger people. The new study shows that some ageing brains also retain this ability to adapt, even though it seems to decrease with advancing age. Furthermore, the results indicate that changes in memory performance resulting from physical exercise are closely linked to changes in brain perfusion.

“Ultimately, we aim to develop measures to purposefully counteract dementia such as Alzheimer’s disease. This is why we want to understand the effects of physical exercise on the brain and the related neurobiological mechanisms. This is essential for developing treatments that are truly effective,” is how Professor Emrah Düzel, site speaker of the DZNE in Magdeburg and director of the Institute of Cognitive Neurology and Dementia Research at the University of Magdeburg, explains the background to the study.

The goal: new brain cells

The researchers’ goal is to cause new nerve cells to grow in the brain. This is how they intend to counter the loss of neurons typical of dementia. “The human brain is able to change and evolve throughout our lives. New nerve cells can form even in adult brains,” says Düzel. “Our aim is to stimulate this so-called neurogenesis. We don’t yet know whether our training methods promote the development of new brain cells. However, fundamental research shows that the formation of new brain cells often goes hand in hand with improved brain perfusion.”

Changes in the hippocampus

Indeed, it did turn out that the treadmill exercise sessions caused more blood to reach the hippocampus in younger participants. “This improves the supply of oxygen and nutrients and may also have other positive effects on the brain’s metabolism,” says the neuroscientist. “However, we have also seen that the effect of the training decreases with age. It is less effective in people aged over 70 than in people in their early 60s. It will be an important goal of our research to understand the causes for this and to find remedies.”

Düzel adds: “It is encouraging to see that visual memory improved as brain perfusion increased. However, effective treatments would also have to affect other brain functions. In our study, the effect was limited to visual short-term memory.”

A combined training for body and mind

Other experiments are now under way in Magdeburg in which test participants are sent on an unusual kind of scavenger hunt: they are assigned the task of finding objects concealed in a computer-generated landscape which is pictured on a large screen. Movement control in this virtual world is done with the help of a treadmill. “This complex situation makes high demands on motor skills and sense of orientation,” explains Düzel. “It challenges both the brain as well as the muscles.”

In the long term, the scientists aim to include people in the early stages of Alzheimer’s disease in their study program. “We are looking for ways of delaying or even stopping the progression of the disease. And we are also researching methods of prevention,” emphasizes Düzel. “Connecting physical activity and mental exercise may have a broad impact, and combined training might become a therapeutic approach. However, this has yet to be shown. In fact, our current results suggest that we may need pharmacological treatments to make exercise more effective.”

Filed under physical activity exercise aging dementia memory hippocampus brain cells neuroscience science

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Exercise key to warding off dementia
EXERCISE is one of the best ways to protect against dementia in later life and the earlier you start, the greater the effect, research suggests.
Participating in intellectually stimulating leisure activities, paid work, volunteer work or study can also help protect against memory loss and reduce the risk of developing Alzheimer’s disease.
UWA adjunct clinical professor Nicola Lautenschlager, who led a review of strategies to delay cognitive decline, says there is a growing body of evidence that suggests exercise is beneficial for brain health.
"The knowledge we have so far basically makes it very clear that regular physical activity, even at an older age, can be very beneficial for protecting cognition," she says.
"Beyond that it’s also very effective for protecting or maintaining mental health, especially in relation to symptoms of depression or anxiety."
Prof Lautenschlager, who is based at the University of Melbourne, says older people who are well enough are advised to do 150 minutes of physical activity a week, such as going for walks.
"When it comes [to] brain health…it would be good if the walking speed isn’t very slow, so it shouldn’t be a stroll but rather what we call moderate pace," she says.
"Research has shown that the level of physical activity has to have a certain intensity so that the brain benefits."
Enjoyable hobbies key to brain health
Hobbies that keep the brain active, such as playing an instrument, going to concerts or joining a book club, can also be very helpful as long as it is an activity a person enjoys, Prof Lautenschlager says.
"The minute you prescribe an activity they hate doing…most likely the effect in terms of being beneficial for brain health is lost," she says.
"It produces so much stress in the body not wanting to do it that the stress is more harmful than the benefit of keeping the brain active."
Prof Lautenschlager says middle age is a crucial time for making lifestyle decisions that will determine a person’s health in later life.
"Usually we are talking about when you move into your 30s, definitely the 40s and also still the 50s," she says.
"Things like a high blood pressure or carrying too much weight, if you do that in these decades, it seems to harm the brain long-term in terms of how healthy a person is in their 70s or 80s."
Ideally people should aim for a healthy lifestyle from childhood but luckily research shows lifestyle changes still have an effect on brain health if a person is already old, Prof Lautenschlager says.
"Even programs…with seniors in their 70s and 80s can still make a difference," she says.
The research was published this month in the journal Maturitas.

Exercise key to warding off dementia

EXERCISE is one of the best ways to protect against dementia in later life and the earlier you start, the greater the effect, research suggests.

Participating in intellectually stimulating leisure activities, paid work, volunteer work or study can also help protect against memory loss and reduce the risk of developing Alzheimer’s disease.

UWA adjunct clinical professor Nicola Lautenschlager, who led a review of strategies to delay cognitive decline, says there is a growing body of evidence that suggests exercise is beneficial for brain health.

"The knowledge we have so far basically makes it very clear that regular physical activity, even at an older age, can be very beneficial for protecting cognition," she says.

"Beyond that it’s also very effective for protecting or maintaining mental health, especially in relation to symptoms of depression or anxiety."

Prof Lautenschlager, who is based at the University of Melbourne, says older people who are well enough are advised to do 150 minutes of physical activity a week, such as going for walks.

"When it comes [to] brain health…it would be good if the walking speed isn’t very slow, so it shouldn’t be a stroll but rather what we call moderate pace," she says.

"Research has shown that the level of physical activity has to have a certain intensity so that the brain benefits."

Enjoyable hobbies key to brain health

Hobbies that keep the brain active, such as playing an instrument, going to concerts or joining a book club, can also be very helpful as long as it is an activity a person enjoys, Prof Lautenschlager says.

"The minute you prescribe an activity they hate doing…most likely the effect in terms of being beneficial for brain health is lost," she says.

"It produces so much stress in the body not wanting to do it that the stress is more harmful than the benefit of keeping the brain active."

Prof Lautenschlager says middle age is a crucial time for making lifestyle decisions that will determine a person’s health in later life.

"Usually we are talking about when you move into your 30s, definitely the 40s and also still the 50s," she says.

"Things like a high blood pressure or carrying too much weight, if you do that in these decades, it seems to harm the brain long-term in terms of how healthy a person is in their 70s or 80s."

Ideally people should aim for a healthy lifestyle from childhood but luckily research shows lifestyle changes still have an effect on brain health if a person is already old, Prof Lautenschlager says.

"Even programs…with seniors in their 70s and 80s can still make a difference," she says.

The research was published this month in the journal Maturitas.

Filed under exercise aging dementia alzheimer's disease cognitive decline neuroscience science

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Decreased ability to identify odors can predict death

For older adults, being unable to identify scents is a strong predictor of death within five years, according to a study published October 1, 2014, in the journal PLOS ONE. Thirty-nine percent of study subjects who failed a simple smelling test died during that period, compared to 19 percent of those with moderate smell loss and just 10 percent of those with a healthy sense of smell.

image

The hazards of smell loss were “strikingly robust,” the researchers note, above and beyond most chronic diseases. Olfactory dysfunction was better at predicting mortality than a diagnosis of heart failure, cancer or lung disease. Only severe liver damage was a more powerful predictor of death. For those already at high risk, lacking a sense of smell more than doubled the probability of death.

"We think loss of the sense of smell is like the canary in the coal mine," said the study’s lead author Jayant M. Pinto, MD, an associate professor of surgery at the University of Chicago who specializes in the genetics and treatment of olfactory and sinus disease. "It doesn’t directly cause death, but it’s a harbinger, an early warning that something has gone badly wrong, that damage has been done. Our findings could provide a useful clinical test, a quick and inexpensive way to identify patients most at risk."

The study was part of the National Social Life, Health and Aging Project (NSHAP), the first in-home study of social relationships and health in a large, nationally representative sample of men and women ages 57 to 85.

In the first wave of NSHAP, conducted in 2005-06, professional survey teams from the independent research organization NORC at the University of Chicago used a well-validated test — adapted by Martha K. McClintock, PhD, the study’s senior author — for this field survey of 3,005 participants. It measured their ability to identify five distinct common odors.

The modified smell tests used “Sniffin’Sticks,” odor-dispensing devices that resemble a felt-tip pen but are loaded with aromas rather than ink. Subjects were asked to identify each smell, one at a time, from a set of four choices. The five odors, in order of increasing difficulty, were peppermint, fish, orange, rose and leather.

Measuring smell with this test, they learned that:

  • Almost 78 percent of those tested were classified as “normosmic,” having normal smelling; 45.5 percent correctly identified five out of five odors and 29 percent identified four out of five.
  • Almost 20 percent were considered “hyposmic.” They got two or three out of five correct.
  • The remaining 3.5 percent were labelled “anosmic.” They could identify just one of the five scents (2.4%), or none (1.1%).

The interviewers also assessed participants’ age, physical and mental health, social and financial resources, education, and alcohol or substance abuse through structured interviews, testing and questionnaires. As expected, performance on the scent test declined steadily with age; 64 percent of 57-year-olds correctly identified all five smells. That fell to 25 percent of 85-year-olds.

In the second wave, during 2010-11, the survey team carefully confirmed which participants were still alive. During that five-year gap, 430 (12.5%) of the original 3005 study subjects had died; 2,565 were still alive.

When the researchers adjusted for demographic variables such as age, gender, socioeconomic status (as measured by education or assets), overall health, and race, those with greater smell loss when first tested were substantially more likely to have died five years later. Even mild smell loss was associated with greater risk.

"This evolutionarily ancient special sense may signal a key mechanism that affects human longevity," noted McClintock, the David Lee Shillinglaw Distinguished Service Professor of Psychology, who has studied olfactory and pheromonal communication throughout her career.

Age-related smell loss can have a substantial impact on lifestyle and wellbeing, according to Pinto, a member of the university’s otolaryngology-head and neck surgery team. “Smells impact how foods taste. Many people with smell deficits lose the joy of eating. They make poor food choices, get less nutrition. They can’t tell when foods have spoiled or detect odors that signal danger, like a gas leak or smoke. They may not notice lapses in personal hygiene.”

"Of all human senses," Pinto said, "smell is the most undervalued and underappreciated — until it’s gone."

Precisely how smell loss contributes to mortality is unclear. “Obviously, people don’t die just because their olfactory system is damaged,” McClintock said.

The research team, which includes biopsychologists, physicians, sociologists and statisticians, is considering several hypotheses. The olfactory nerve, the only cranial nerve directly exposed to the environment, may serve as a conduit, they suggest, exposing the central nervous system to pollution, airborne toxins, pathogens or particulate matter.

McClintock noted that the olfactory system also has stem cells which self-regenerate, so “a decrease in the ability to smell may signal a decrease in the body’s ability to rebuild key components that are declining with age and lead to all-cause mortality.”

(Source: uchospitals.edu)

Filed under sense of smell olfaction olfactory system aging neuroscience science

516 notes

Memory loss associated with Alzheimer’s reversed for first time
Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.
The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.
The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.
In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.
Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.
While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”
The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.
The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.
Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.
“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well—the drug may have worked, a single “hole” may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”
Bredesen’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:
(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.
The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”
The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.
Cognitive decline is a major concern of the aging population. Already, Alzheimer’s disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it’s estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease is on the rise—recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.
(Image: Corbis)

Memory loss associated with Alzheimer’s reversed for first time

Since its first description over 100 years ago, Alzheimer’s disease has been without effective treatment. That may finally be about to change: in the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants, including the ones above, displayed subjective or objective improvement in their memories beginning within 3-to-6 months after the program’s start. Of the six patients who had to discontinue working or were struggling with their jobs at the time they joined the study, all were able to return to work or continue working with improved performance. Improvements have been sustained, and as of this writing the longest patient follow-up is two and one-half years from initial treatment. These first ten included patients with memory loss associated with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI; when a patient reports cognitive problems). One patient, diagnosed with late stage Alzheimer’s, did not improve.

The study, which comes jointly from the UCLA Mary S. Easton Center for Alzheimer’s Disease Research and the Buck Institute for Research on Aging, is the first to suggest that memory loss in patients may be reversed, and improvement sustained, using a complex, 36-point therapeutic program that involves comprehensive changes in diet, brain stimulation, exercise, optimization of sleep, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.

The findings, published in the current online edition of the journal Aging, “are very encouraging. However, at the current time the results are anecdotal, and therefore a more extensive, controlled clinical trial is warranted,” said Dale Bredesen, the Augustus Rose Professor of Neurology and Director of the Easton Center at UCLA, a professor at the Buck Institute, and the author of the paper.

In the case of Alzheimer’s disease, Bredesen notes, there is not one drug that has been developed that stops or even slows the disease’s progression, and drugs have only had modest effects on symptoms. “In the past decade alone, hundreds of clinical trials have been conducted for Alzheimer’s at an aggregate cost of over a billion dollars, without success,” he said.

Other chronic illnesses such as cardiovascular disease, cancer, and HIV, have been improved through the use of combination therapies, he noted. Yet in the case of Alzheimer’s and other memory disorders, comprehensive combination therapies have not been explored. Yet over the past few decades, genetic and biochemical research has revealed an extensive network of molecular interactions involved in AD pathogenesis. “That suggested that a broader-based therapeutics approach, rather than a single drug that aims at a single target, may be feasible and potentially more effective for the treatment of cognitive decline due to Alzheimer’s,” said Bredesen.

While extensive preclinical studies from numerous laboratories have identified single pathogenetic targets for potential intervention, in human studies, such single target therapeutic approaches have not borne out. But, said Bredesen, it’s possible addressing multiple targets within the network underlying AD may be successful even when each target is affected in a relatively modest way. “In other words,” he said, “the effects of the various targets may be additive, or even synergistic.”

The uniform failure of drug trials in Alzheimer’s influenced Bredesen’s research to get a better understanding of the fundamental nature of the disease. His laboratory has found evidence that Alzheimer’s disease stems from an imbalance in nerve cell signaling: in the normal brain, specific signals foster nerve connections and memory making, while balancing signals support memory loss, allowing irrelevant information to be forgotten. But in Alzheimer’s disease, the balance of these opposing signals is disturbed, nerve connections are suppressed, and memories are lost.

The model of multiple targets and an imbalance in signaling runs contrary to the popular dogma that Alzheimer’s is a disease of toxicity, caused by the accumulation of sticky plaques in the brain. Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain – as part of a larger set of molecules that promotes signals that cause nerve connections to lapse. Thus the increase in the peptide that occurs in Alzheimer’s disease shifts the memory-making vs. memory-breaking balance in favor of memory loss.

Given all this, Bredesen thought that rather than a single targeted agent, the solution might be a systems type approach, the kind that is in line with the approach taken with other chronic illnesses—a multiple-component system.

“The existing Alzheimer’s drugs affect a single target, but Alzheimer’s disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well—the drug may have worked, a single “hole” may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

Bredesen’s approach is personalized to the patient, based on extensive testing to determine what is affecting the plasticity signaling network of the brain. As one example, in the case of the patient with the demanding job who was forgetting her way home, her therapeutic program consisted of some, but not all of the components involved with Bredesen’s therapeutic program, and included:

(1) eliminating all simple carbohydrates, leading to a weight loss of 20 pounds; (2) eliminating gluten and processed food from her diet, with increased vegetables, fruits, and non-farmed fish; (3) to reduce stress, she began yoga; (4) as a second measure to reduce the stress of her job, she began to meditate for 20 minutes twice per day; (5) she took melatonin each night; (6) she increased her sleep from 4-5 hours per night to 7-8 hours per night; (7) she took methylcobalamin each day; (8) she took vitamin D3 each day; (9) fish oil each day; (10) CoQ10 each day; (11) she optimized her oral hygiene using an electric flosser and electric toothbrush; (12) following discussion with her primary care provider, she reinstated hormone replacement therapy that had been discontinued; (13) she fasted for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime; (14) she exercised for a minimum of 30 minutes, 4-6 days per week.

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results are anecdotal, and therefore a more extensive, controlled clinical trial is needed.

The downside to this program is its complexity. It is not easy to follow, with the burden falling on the patients and caregivers, and none of the patients were able to stick to the entire protocol. The significant diet and lifestyle changes, and multiple pills required each day, were the two most common complaints. The good news, though, said Bredesen, are the side effects: “It is noteworthy that the major side effect of this therapeutic system is improved health and an optimal body mass index, a stark contrast to the side effects of many drugs.”

The results for nine of the 10 patients reported in the paper suggest that memory loss may be reversed, and improvement sustained with this therapeutic program, said Bredesen. “This is the first successful demonstration,” he noted, but he cautioned that the results need to be replicated. “The current, anecdotal results require a larger trial, not only to confirm or refute the results reported here, but also to address key questions raised, such as the degree of improvement that can be achieved routinely, how late in the course of cognitive decline reversal can be effected, whether such an approach may be effective in patients with familial Alzheimer’s disease, and last, how long improvement can be sustained,” he said.

Cognitive decline is a major concern of the aging population. Already, Alzheimer’s disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it’s estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer’s disease is on the rise—recent estimates suggest that AD has become the third leading cause of death in the United States behind cardiovascular disease and cancer.

(Image: Corbis)

Filed under alzheimer's disease memory loss aging cognitive decline neuroscience science

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Scientists Identify the Signature of Aging in the Brain

How the brain ages is still largely an open question – in part because this organ is mostly insulated from direct contact with other systems in the body, including the blood and immune systems. In research that was recently published in Science, Weizmann Institute researchers Prof. Michal Schwartz of the Neurobiology Department and Dr. Ido Amit of Immunology Department found evidence of a unique “signature” that may be the “missing link” between cognitive decline and aging. The scientists believe that this discovery may lead, in the future, to treatments that can slow or reverse cognitive decline in older people.

image

(Image caption: Immunofluorescence microscope image of the choroid plexus. Epithelial cells are in green and chemokine proteins (CXCL10) are in red)

Until a decade ago, scientific dogma held that the blood-brain barrier prevents the blood-borne immune cells from attacking and destroying brain tissue. Yet in a long series of studies, Schwartz’s group had shown that the immune system actually plays an important role both in healing the brain after injury and in maintaining the brain’s normal functioning. They have found that this brain-immune interaction occurs across a barrier that is actually a unique interface within the brain’s territory.

This interface, known as the choroid plexus, is found in each of the brain’s four ventricles, and it separates the blood from the cerebrospinal fluid. Schwartz: “The choroid plexus acts as a ‘remote control’ for the immune system to affect brain activity. Biochemical ‘danger’ signals released from the brain are sensed through this interface; in turn, blood-borne immune cells assist by communicating with the choroid plexus. This cross-talk is important for preserving cognitive abilities and promoting the generation of new brain cells.”

This finding led Schwartz and her group to suggest that cognitive decline over the years may be connected not only to one’s “chronological age” but also to one’s “immunological age,” that is, changes in immune function over time might contribute to changes in brain function – not necessarily in step with the count of one’s years.

To test this theory, Schwartz and research students Kuti Baruch and Aleksandra Deczkowska teamed up with Amit and his research group in the Immunology Department. The researchers used next-generation sequencing technology to map changes in gene expression in 11 different organs, including the choroid plexus, in both young and aged mice, to identify and compare pathways involved in the aging process.

That is how they identified a strikingly unique “signature of aging” that exists solely in the choroid plexus – not in the other organs. They discovered that one of the main elements of this signature was interferon beta – a protein that the body normally produces to fight viral infection. This protein appears to have a negative effect on the brain: When the researchers injected an antibody that blocks interferon beta activity into the cerebrospinal fluid of the older mice, their cognitive abilities were restored, as was their ability to form new brain cells. The scientists were also able to identify this unique signature in elderly human brains. The scientists hope that this finding may, in the future, help prevent or reverse cognitive decline in old age, by finding ways to rejuvenate the “immunological age” of the brain.

(Source: wis-wander.weizmann.ac.il)

Filed under aging cognitive decline brain function blood-brain barrier choroid plexus gene expression neuroscience science

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Compound from hops aids cognitive function in young animals

Xanthohumol, a type of flavonoid found in hops and beer, has been shown in a new study to improve cognitive function in young mice, but not in older animals.

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The research was just published in Behavioral Brain Research by scientists from the Linus Pauling Institute and College of Veterinary Medicine at Oregon State University. It’s another step toward understanding, and ultimately reducing the degradation of memory that happens with age in many mammalian species, including humans.

Flavonoids are compounds found in plants that often give them their color. The study of them – whether in blueberries, dark chocolate or red wine - has increased in recent years due to their apparent nutritional benefits, on issues ranging from cancer to inflammation or cardiovascular disease. Several have also been shown to be important in cognition.

Xanthohumol has been of particular interest because of possible value in treating metabolic syndrome, a condition associated with obesity, high blood pressure and other concerns, including age-related deficits in memory. The compound has been used successfully to lower body weight and blood sugar in a rat model of obesity.

The new research studied use of xanthohumol in high dosages, far beyond what could be obtained just by diet. At least in young animals, it appeared to enhance their ability to adapt to changes in the environment. This cognitive flexibility was tested with a special type of maze designed for that purpose.

“Our goal was to determine whether xanthohumol could affect a process we call palmitoylation, which is a normal biological process but in older animals may become harmful,” said Daniel Zamzow, a former OSU doctoral student and now a lecturer at the University of Wisconsin/Rock County.

“Xanthohumol can speed the metabolism, reduce fatty acids in the liver and, at least with young mice, appeared to improve their cognitive flexibility, or higher level thinking,” Zamzow said. “Unfortunately it did not reduce palmitoylation in older mice, or improve their learning or cognitive performance, at least in the amounts of the compound we gave them.”

Kathy Magnusson, a professor in the OSU Department of Biomedical Sciences, principal investigator with the Linus Pauling Institute and corresponding author on this study, said that xanthohumol continues to be of significant interest for its biological properties, as are many other flavonoids.

“This flavonoid and others may have a function in the optimal ability to form memories,” Magnusson said. “Part of what this study seems to be suggesting is that it’s important to begin early in life to gain the full benefits of healthy nutrition.”

It’s also important to note, Magnusson said, that the levels of xanthohumol used in this study were only possible with supplements. As a fairly rare micronutrient, the only normal dietary source of it would be through the hops used in making beer, and “a human would have to drink 2000 liters of beer a day to reach the xanthohumol levels we used in this research.”

In this and other research, Magnusson’s research has primarily focused on two subunits of the NMDA receptor, called GluN1 and GluN2B. Their decline with age appears to be related to the decreased ability to form and quickly recall memories.

In humans, many adults start to experience deficits in memory around the age of 50, and some aspects of cognition begin to decline around age 40, the researchers noted in their report.

(Source: oregonstate.edu)

Filed under cognitive function xanthohumol memory aging NMDA receptor animal studies neuroscience science

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Study links physical activity in older adults to brain white-matter integrity
Like everything else in the body, the white-matter fibers that allow communication between brain regions also decline with age. In a new study, researchers found a strong association between the structural integrity of these white-matter tracts and an older person’s level of daily activity – not just the degree to which he or she engaged in moderate or vigorous exercise, but also whether the person was sedentary the rest of the time.
The study, reported in the journal PLOS ONE, tracked physical activity in 88 healthy but “low-fit” participants aged 60 to 78. The participants agreed to wear accelerometers during most of their waking hours over the course of a week, and also submitted to brain imaging.
“To our knowledge, this is the first study of its kind that uses an objective measure of physical activity along with multiple measures of brain structure,” said University of Illinois postdoctoral researcher Agnieszka Burzynska, who conducted the research with U. of I. Beckman Institute director Arthur Kramer and kinesiology and community health professor Edward McAuley.
Most studies ask subjects to describe how much physical activity they get, which is subjective and imprecise, Burzynska said. The accelerometer continuously tracks a person’s movement, “so it’s not what they say they do or what they think they do, but we have measured what they are actually doing,” she said.
The researchers assumed that participants’ activity levels over a week accurately reflected their overall engagement, or lack of engagement, in physical activity.
The study also relied on two types of brain imaging. The first, diffusion tensor imaging, offers insight into the structural integrity of a tissue by revealing how water is diffused in the tissue. The second method looks for age-related changes in white matter, called lesions. Roughly 95 percent of adults aged 65 and older have such lesions, Burzynska said. While they are a normal part of aging, their early onset or rapid accumulation may spell trouble, she said.
The team found that the brains of older adults who regularly engaged in moderate-to-vigorous exercise generally “showed less of the white-matter lesions,” Burzynska said.
The association between physical activity and white-matter structural integrity was region-specific, the researchers reported. Older adults who engaged more often in light physical activity had greater structural integrity in the white-matter tracts of the temporal lobes, which lie behind the ears and play a key role in memory, language, and the processing of visual and auditory information.
In contrast, those who spent more time sitting had lower structural integrity in the white-matter tracts connecting the hippocampus, “a structure crucial for learning and memory,” Burzynska said.
“This relationship between the integrity of tracts connecting the hippocampus and sedentariness is significant even when we control for age, gender and aerobic fitness,” she said. “It suggests that the physiological effect of sitting too much, even if you still exercise at the end of the day for half an hour, will have a detrimental effect on your brain.”
The findings suggest that engaging in physical activity and avoiding a sedentary lifestyle are both important for brain health in older age, Burzynska said.
“We hope that this will encourage people to take better care of their brains by being more active,” she said.

Study links physical activity in older adults to brain white-matter integrity

Like everything else in the body, the white-matter fibers that allow communication between brain regions also decline with age. In a new study, researchers found a strong association between the structural integrity of these white-matter tracts and an older person’s level of daily activity – not just the degree to which he or she engaged in moderate or vigorous exercise, but also whether the person was sedentary the rest of the time.

The study, reported in the journal PLOS ONE, tracked physical activity in 88 healthy but “low-fit” participants aged 60 to 78. The participants agreed to wear accelerometers during most of their waking hours over the course of a week, and also submitted to brain imaging.

“To our knowledge, this is the first study of its kind that uses an objective measure of physical activity along with multiple measures of brain structure,” said University of Illinois postdoctoral researcher Agnieszka Burzynska, who conducted the research with U. of I. Beckman Institute director Arthur Kramer and kinesiology and community health professor Edward McAuley.

Most studies ask subjects to describe how much physical activity they get, which is subjective and imprecise, Burzynska said. The accelerometer continuously tracks a person’s movement, “so it’s not what they say they do or what they think they do, but we have measured what they are actually doing,” she said.

The researchers assumed that participants’ activity levels over a week accurately reflected their overall engagement, or lack of engagement, in physical activity.

The study also relied on two types of brain imaging. The first, diffusion tensor imaging, offers insight into the structural integrity of a tissue by revealing how water is diffused in the tissue. The second method looks for age-related changes in white matter, called lesions. Roughly 95 percent of adults aged 65 and older have such lesions, Burzynska said. While they are a normal part of aging, their early onset or rapid accumulation may spell trouble, she said.

The team found that the brains of older adults who regularly engaged in moderate-to-vigorous exercise generally “showed less of the white-matter lesions,” Burzynska said.

The association between physical activity and white-matter structural integrity was region-specific, the researchers reported. Older adults who engaged more often in light physical activity had greater structural integrity in the white-matter tracts of the temporal lobes, which lie behind the ears and play a key role in memory, language, and the processing of visual and auditory information.

In contrast, those who spent more time sitting had lower structural integrity in the white-matter tracts connecting the hippocampus, “a structure crucial for learning and memory,” Burzynska said.

“This relationship between the integrity of tracts connecting the hippocampus and sedentariness is significant even when we control for age, gender and aerobic fitness,” she said. “It suggests that the physiological effect of sitting too much, even if you still exercise at the end of the day for half an hour, will have a detrimental effect on your brain.”

The findings suggest that engaging in physical activity and avoiding a sedentary lifestyle are both important for brain health in older age, Burzynska said.

“We hope that this will encourage people to take better care of their brains by being more active,” she said.

Filed under physical activity exercise white matter brain structure neuroimaging aging neuroscience science

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