Posts tagged dementia
Articles and news from the latest research reports.
New insight on why people with Down syndrome invariably develop Alzheimer’s disease
A new study by researchers at Sanford-Burnham Medical Research Institute reveals the process that leads to changes in the brains of individuals with Down syndrome—the same changes that cause dementia in Alzheimer’s patients. The findings, published in Cell Reports, have important implications for the development of treatments that can prevent damage in neuronal connectivity and brain function in Down syndrome and other neurodevelopmental and neurodegenerative conditions, including Alzheimer’s disease.
Down syndrome is characterized by an extra copy of chromosome 21 and is the most common chromosome abnormality in humans. It occurs in about one per 700 babies in the United States, and is associated with a mild to moderate intellectual disability. Down syndrome is also associated with an increased risk of developing Alzheimer’s disease. By the age of 40, nearly 100 percent of all individuals with Down syndrome develop the changes in the brain associated with Alzheimer’s disease, and approximately 25 percent of people with Down syndrome show signs of Alzheimer’s-type dementia by the age of 35, and 75 percent by age 65. As the life expectancy for people with Down syndrome has increased dramatically in recent years—from 25 in 1983 to 60 today—research aimed to understand the cause of conditions that affect their quality of life are essential.
"Our goal is to understand how the extra copy of chromosome 21 and its genes cause individuals with Down syndrome to have a greatly increased risk of developing dementia," said Huaxi Hu, Ph.D., professor in the Degenerative Diseases Program at Sanford-Burnham and senior author of the paper. "Our new study reveals how a protein called sorting nexin 27 (SNX27) regulates the generation of beta-amyloid—the main component of the detrimental amyloid plaques found in the brains of people with Down syndrome and Alzheimer’s. The findings are important because they explain how beta-amyloid levels are managed in these individuals."
Beta-Amyloid, Plaques and Dementia
Xu’s team found that SNX27 regulates beta-amyloid generation. Beta-amyloid is a sticky protein that’s toxic to neurons. The combination of beta-amyloid and dead neurons form clumps in the brain called plaques. Brain plaques are a pathological hallmark of Alzheimer’s disease and are implicated in the cause of the symptoms of dementia.
"We found that SNX27 reduces beta-amyloid generation through interactions with gamma-secretase—an enzyme that cleaves the beta-amyloid precursor protein to produce beta-amyloid," said Xin Wang, Ph.D., a postdoctoral fellow in Xu’s lab and first author of the publication. "When SNX27 interacts with gamma-secretase, the enzyme becomes disabled and cannot produce beta-amyloid. Lower levels of SNX27 lead to increased levels of functional gamma-secretase that in turn lead to increased levels of beta-amyloid."
SNX27’s Role in Brain Function
Previously, Xu and colleagues found that SNX27 deficient mice shared some characteristics with Down syndrome, and that humans with Down syndrome have significantly lower levels of SNX27. In the brain, SNX27 maintains certain receptors on the cell surface—receptors that are necessary for neurons to fire properly. When levels of SNX27 are reduced, neuron activity is impaired, causing problems with learning and memory. Importantly, the research team found that by adding new copies of the SNX27 gene to the brains of Down syndrome mice, they could repair the memory deficit in the mice.
The researchers went on to reveal how lower levels of SNX27 in Down syndrome are the result of an extra copy of an RNA molecule encoded by chromosome 21 called miRNA-155. miRNA-155 is a small piece of genetic material that doesn’t code for protein, but instead influences the production of SNX27.
With the current study, researchers can piece the entire process together—the extra copy of chromosome 21 causes elevated levels of miRNA-155 that in turn lead to reduced levels of SNX27. Reduced levels of SNX27 lead to an increase in the amount of active gamma-secretase causing an increase in the production of beta-amyloid and the plaques observed in affected individuals.
"We have defined a rather complex mechanism that explains how SNX27 levels indirectly lead to beta-amyloid," said Xu. "While there may be many factors that contribute to Alzheimer’s characteristics in Down syndrome, our study supports an approach of inhibiting gamma-secretase as a means to prevent the amyloid plaques in the brain found in Down syndrome and Alzheimer’s."
"Our next step is to develop and implement a screening test to identify molecules that can reduce the levels of miRNA-155 and hence restore the level of SNX27, and find molecules that can enhance the interaction between SNX27 and gamma-secretase. We are working with the Conrad Prebys Center for Chemical Genomics at Sanford-Burnham to achieve this," added Xu.
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.
New Research on Walnuts and the Fight Against Alzheimer’s Disease
A new animal study published in the Journal of Alzheimer’s Disease indicates that a diet including walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer’s disease.
Research led by Abha Chauhan, PhD, head of the Developmental Neuroscience Laboratory at the New York State Institute for Basic Research in Developmental Disabilities (IBR), found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet.
The researchers suggest that the high antioxidant content of walnuts (3.7 mmol/ounce) may have been a contributing factor in protecting the mouse brain from the degeneration typically seen in Alzheimer’s disease. Oxidative stress and inflammation are prominent features in this disease, which affects more than five million Americans.
“These findings are very promising and help lay the groundwork for future human studies on walnuts and Alzheimer’s disease – a disease for which there is no known cure,” said lead researcher Dr. Abha Chauhan, PhD. “Our study adds to the growing body of research that demonstrates the protective effects of walnuts on cognitive functioning.”
The research group examined the effects of dietary supplementation on mice with 6 percent or 9 percent walnuts, which are equivalent to 1 ounce and 1.5 ounces per day, respectively, of walnuts in humans. This research stemmed from a previous cell culture study led by Dr. Chauhan that highlighted the protective effects of walnut extract against the oxidative damage caused by amyloid beta protein. This protein is the major component of amyloid plaques that form in the brains of those with Alzheimer’s disease.
Someone in the United States develops Alzheimer’s disease every 67 seconds, and the number of Americans with Alzheimer’s disease and other dementias are expected to rapidly escalate in coming years as the baby boom generation ages. By 2050, the number of people age 65 and older with Alzheimer’s disease may nearly triple, from five million to as many as 16 million, emphasizing the importance of determining ways to prevent, slow or stop the disease. Estimated total payments in 2014 for all individuals with Alzheimer’s disease and other dementias are $214 billion.
Walnuts have other nutritional benefits as they contain numerous vitamins and minerals and are the only nut that contains a significant source of alpha-linolenic acid (ALA) (2.5 grams per ounce), an omega-3 fatty acid with heart and brain-health benefits. The researchers also suggest that ALA may have played a role in improving the behavioral symptoms seen in the study.
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.”
![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.](http://31.media.tumblr.com/6aefc29f7bda88b832996d3c6bc84bc3/tumblr_ndc345d4151rog5d1o1_500.jpg)
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.
MRI Technique Detects Evidence of Cognitive Decline Before Symptoms Appear
A magnetic resonance imaging (MRI) technique can detect signs of cognitive decline in the brain even before symptoms appear, according to a new study published online in the journal Radiology. The technique has the potential to serve as a biomarker in very early diagnosis of preclinical dementia.
The World Health Organization estimates that dementia affects more than 35 million people worldwide, a number expected to more than double by 2030. Problems in the brain related to dementia, such as reduced blood flow, might be present for years but are not evident because of cognitive reserve, a phenomenon where other parts of the brain compensate for deficits in one area. Early detection of cognitive decline is critical, because treatments for Alzheimer’s disease, the most common type of dementia, are most effective in this early phase.
Researchers recently studied arterial spin labeling (ASL), a promising MRI technique that doesn’t require injection of a contrast agent. ASL measures brain perfusion, or penetration of blood into the tissue.
"ASL MRI is simple to perform, doesn’t require special equipment and only adds a few minutes to the exam," said study author Sven Haller, M.D., from the University of Geneva in Geneva, Switzerland.
The study group included 148 healthy elderly participants and 65 people with mild cognitive impairment (MCI). The participants underwent brain MRI and a neuropsychological assessment, a common battery of tests used to determine cognitive ability.
Of the 148 healthy individuals, 75 remained stable, while 73 deteriorated cognitively at 18 months clinical follow-up. Those who deteriorated had shown reduced perfusion at their baseline ASL MRI exams, particularly in the posterior cingulate cortex, an area in the middle of the brain that is associated with the default mode network, the neural network that is active when the brain is not concentrating on a specific task. Declines in this network are seen in MCI patients and are more pronounced in those with Alzheimer’s disease.
The pattern of reduced perfusion in the brains of healthy individuals who went on to develop cognitive deficits was similar to that of patients with MCI.
"There is a known close link between neural activity and brain perfusion in the posterior cingulate cortex," Dr. Haller said. "Less perfusion indicates decreased neural activity."
The results suggest that individuals with decreased perfusion detected with ASL MRI may temporarily maintain their cognitive status through the mobilization of their cognitive reserve, but will eventually develop subtle cognitive deficits.
Previous research done with positron emission tomography (PET), the current gold standard for brain metabolism imaging, found that patients with Alzheimer’s disease had reduced metabolism in the same area of the brain where the perfusion abnormalities were found using ASL MRI. This points to a close link between brain metabolism and perfusion, according to Dr. Haller.
ASL MRI has potential as a standalone test or as an adjunct to PET for dementia screening, Dr. Haller said. While PET can identify markers of Alzheimer’s disease in the brain and cerebrospinal fluid, it exposes the patient to radiation. ASL does not expose the patient to radiation and is easy to perform in routine clinical settings.
"ASL might replace the classic yet unspecific fluordesoxyglucose PET that measures brain metabolism. Instead, PET could be done with the new and specific amyloid PET tracers," Dr. Haller said.
The results also support a role for ASL MRI as an alternative to neuropsychological testing.
The researchers plan to perform follow-up studies on the patient group to learn more about ASL and long-term cognitive changes.
Worry, jealousy, moodiness linked to higher risk of Alzheimer’s in women
Women who are anxious, jealous, or moody and distressed in middle age may be at a higher risk of developing Alzheimer’s disease later in life, according to a nearly 40-year-long study published in the October 1, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
"Most Alzheimer’s research has been devoted to factors such as education, heart and blood risk factors, head trauma, family history and genetics," said study author Lena Johannsson, PhD, of the University of Gothenburg in Gothenburg, Sweden. "Personality may influence the individual’s risk for dementia through its effect on behavior, lifestyle or reactions to stress."
For the study, 800 women with an average age of 46 were followed for 38 years and given personality tests that looked at their level of neuroticism and extraversion or introversion, along with memory tests. Of those, 19 percent developed dementia.
Neuroticism involves being easily distressed and personality traits such as worrying, jealousy or moodiness. People who are neurotic are more likely to express anger, guilt, envy, anxiety or depression. Introversion is described as shyness and reserve and extraversion is associated with being outgoing.
The women were also asked if they had experienced any period of stress that lasted one month or longer in their work, health, or family situation. Stress referred to feelings of irritability, tension, nervousness, fear, anxiety or sleep disturbances. Responses were categorized as zero to five, with zero representing never experiencing any period of stress, to five, experiencing constant stress during the last five years. Women who chose responses from 3 and 5 were considered to have distress.
The study found that women who scored highest on the tests for neuroticism had double the risk of developing dementia compared to those who scored lowest on the tests. However, the link depended on long-standing stress.
Being either withdrawn or outgoing did not appear to raise dementia risk alone, however, women who were both easily distressed and withdrawn had the highest risk of Alzheimer’s disease in the study. A total of 16 of the 63 women, or 25 percent, who were easily distressed and withdrawn developed Alzheimer’s disease, compared to eight out of the 64 people, or 13 percent, of those who were not easily distressed and were outgoing.
(Image: Corbis)
Protein that Causes Frontotemporal Dementia also Implicated in Alzheimer’s Disease
Researchers at the Gladstone Institutes have shown that low levels of the protein progranulin in the brain can increase the formation of amyloid-beta plaques (a hallmark of Alzheimer’s disease), cause neuroinflammation, and worsen memory deficits in a mouse model of this condition. Conversely, by using a gene therapy approach to elevate progranulin levels, scientists were able to prevent these abnormalities and block cell death in this model.
Progranulin deficiency is known to cause another neurodegenerative disorder, frontotemporal dementia (FTD), but its role in Alzheimer’s disease was previously unclear. Although the two conditions are similar, FTD is associated with greater injury to cells in the frontal cortex, causing behavioral and personality changes, whereas Alzheimer’s disease predominantly affects memory centers in the hippocampus and temporal cortex.
Earlier research showed that progranulin levels were elevated near plaques in the brains of patients with Alzheimer’s disease, but it was unknown whether this effect counteracted or exacerbated neurodegeneration. The new evidence, published today in Nature Medicine, shows that a reduction of the protein can severely aggravate symptoms, while increases in progranulin may be the brain’s attempt at fighting the inflammation associated with the disease.
According to first author S. Sakura Minami, PhD, a postdoctoral fellow at the Gladstone Institutes, “This is the first study providing evidence for a protective role of progranulin in Alzheimer’s disease. Prior research had shown a link between Alzheimer’s and progranulin, but the nature of the association was unclear. Our study demonstrates that progranulin deficiency may promote Alzheimer’s disease, with decreased levels rendering the brain vulnerable to amyloid-beta toxicity.”
In the study, the researchers manipulated several different mouse models of Alzheimer’s disease, genetically raising or lowering their progranulin levels. Reducing progranulin markedly increased amyloid-beta plaque deposits in the brain as well as memory impairments. Progranulin deficiency also triggered an over-active immune response in the brain, which can contribute to neurological disorders. In contrast, increasing progranulin levels via gene therapy effectively lowered amyloid beta levels, protecting against cell toxicity and reversing the cognitive deficits typically seen in these Alzheimer’s models.
These effects appear to be linked to progranulin’s involvement in phagocytosis, a type of cellular house-keeping whereby cells “eat” other dead cells, debris, and large molecules. Low levels of progranulin can impair this process, leading to increased amyloid beta deposition. Conversely, increasing progranulin levels enhanced phagocytosis, decreasing the plaque load and preventing neuron death.
“The profound protective effects of progranulin against both amyloid-beta deposits and cell toxicity have important therapeutic implications,” said senior author Li Gan, PhD, an associate investigator at Gladstone and associate professor of neurology at the University of California, San Francisco. “The next step will be to develop progranulin-enhancing approaches that can be used as potential novel treatments, not only for frontotemporal dementia, but also for Alzheimer’s disease.”
(Source: gladstoneinstitutes.org)
Scientists Develop First Animal Model for ALS Dementia
The first animal model for ALS dementia, a form of ALS that also damages the brain, has been developed by Northwestern Medicine scientists. The advance will allow researchers to directly see the brains of living mice, under anesthesia, at the microscopic level. This will allow direct monitoring of test drugs to determine if they work.
This is one of the latest research findings since the ALS Ice Bucket Challenge heightened interest in the disease and the need for expanded research and funding.
“This new model will allow rapid testing and direct monitoring of drugs in real time,” said Northwestern scientist and study senior author Teepu Siddique, MD. “This will allow scientists to move quickly and accelerate the testing of drug therapies.”
The new mouse model has the pathological hallmarks of the disease in humans with mutations in the genes for UBQLN2 (ubliqulin 2) and SQSTM1 (P62) that Siddique and colleagues identified in 2011. That pathology was linked to all forms of ALS and ALS/dementia.
Dr. Siddique and Han-Xiang Deng, MD, the corresponding authors on the paper, said they have reproduced behavioral, neurophysiological and pathological changes in a mouse that mimic this form of dementia associated with ALS (amyotrophic lateral sclerosis).
Dr. Siddique is the Les Turner ALS Foundation/Herbert C. Wenske Professor of Neurology at Northwestern University Feinberg School of Medicine and a neurologist at Northwestern Memorial Hospital. Dr. Deng is a research professor in Neurology at Feinberg.
The study was published Sept. 22 in the Proceedings of the National Academy of Sciences.
It’s been difficult for scientists to reproduce the genetic mutations of ALS, especially ALS/dementia in animal models, Dr. Siddique noted, which has hampered drug therapy testing.
Five percent or more of ALS cases, also known as Lou Gherig’s disease, also have ALS/dementia.
“ALS with dementia is an even more vicious disease than ALS alone because it attacks the brain causing changes in behavior and language well as causing paralysis,” Dr. Siddique said.
ALS affects an estimated 350,000 people worldwide, with an average survival of three years. In this progressive neurological disorder, the degeneration of neurons leads to muscle weakness and impaired speaking, swallowing and breathing, eventually causing paralysis and death. The associated dementia affects behavior and may affect decision-making, judgment, insight and language.
(Source: feinberg.northwestern.edu)
Think You Have Alzheimer’s? UK Study Suggests You May Be Right
New research by scientists at the University of Kentucky’s Sanders-Brown Center on Aging suggests that people who notice their memory is slipping may be on to something.
The research, led by Richard Kryscio, Ph.D., chair of the Department of of Biostatistics and associate director of the Alzheimer’s Disease Center at UK, appears to confirm that self-reported memory complaints are strong predictors of clinical memory impairment later in life.
Kryscio and his group asked 531 people with an average age of 73 and free of dementia if they had noticed any changes in their memory in the prior year. The participants were also given annual memory and thinking tests for an average of 10 years. After death, participants’ brains were examined for evidence of Alzheimer’s disease.
During the study, 56 percent of the participants reported changes in their memory, at an average age of 82. The study found that participants who reported changes in their memory were nearly three times more likely to develop memory and thinking problems. About one in six participants developed dementia during the study, and 80 percent of those first reported memory changes.
"What’s notable about our study is the time it took for the transition from self-reported memory complaint to dementia or clinical impairment — about 12 years for dementia and nine years for clinical impairment — after the memory complaints began," Kryscio said. "That suggests that there may be a significant window of opportunity for intervention before a diagnosable problem shows up."
Kryscio points out that while these findings add to a growing body of evidence that self-reported memory complaints can be predictive of cognitive impairment later in life, there isn’t cause for immediate alarm if you can’t remember where you left your keys.
"Certainly, someone with memory issues should report it to their doctor so they can be followed. Unfortunately, however, we do not yet have preventative therapies for Alzheimer’s disease or other illnesses that cause memory problems."
The research, which was supported by grants from the National Institutes of Health, the National Institute on Aging, and the National Center for Advancing Translational Sciences, was published in the Sept. 24, 2014, online issue of Neurology.
(Source: uknow.uky.edu)