Posts tagged dementia
Articles and news from the latest research reports.
Gene variant puts women at higher risk of Alzheimer’s than it does men
Carrying a copy of a gene variant called ApoE4 confers a substantially greater risk for Alzheimer’s disease on women than it does on men, according to a new study by researchers at the Stanford University School of Medicine.
The scientists arrived at their findings by analyzing data on large numbers of older individuals who were tracked over time and noting whether they had progressed from good health to mild cognitive impairment — from which most move on to develop Alzheimer’s disease within a few years — or to Alzheimer’s disease itself.
The discovery holds implications for genetic counselors, clinicians and individual patients, as well as for clinical-trial designers. It could also help shed light on the underlying causes of Alzheimer’s disease, a progressive neurological syndrome that robs its victims of their memory and ability to reason. Its incidence increases exponentially after age 65. An estimated one in every eight people past that age in the United States has Alzheimer’s. Experts project that by mid-century, the number of Americans with Alzheimer’s will more than double from the current estimate of 5-6 million.
According to the Alzheimer’s Association, it is already the nation’s most expensive disease, costing more than $200 million annually. (The epidemiology of mild cognitive impairment is fuzzier, but this gateway syndrome is clearly more widespread than Alzheimer’s.)
New mouse model could revolutionize research in Alzheimer’s disease
In a study published today in Nature Neuroscience, a group of researchers led by Takaomi Saido of the RIKEN Brain Science Institute in Japan have reported the creation of two new mouse models of Alzheimer’s disease that may potentially revolutionize research into this disease.
Alzheimer’s disease, the primary cause of dementia in the elderly, imposes a tremendous social and economic burden on modern society. In Japan, the burden of the disease in 2050 is estimated to be a half a trillion US dollars, a figure equivalent to the government’s annual revenues.
Unfortunately, it has proven very difficult to develop drugs capable of ameliorating the disease. After a tremendous burst of progress in the 1990s, the pace of discoveries has slowed. Dr. Saido believes that part of the difficulty is the inadequacy of current mouse models to replicate the real conditions of Alzheimer’s disease and allow an understanding of the underlying mechanisms that lead to neurodegeneration. In fact, much of the research in Alzheimer’s disease over the past decade may be flawed, as it was based on unrealistic models.
The problem with older mouse models is that they overexpress a protein called amyloid precursor protein, or APP, which gives rise to the amyloid-beta (Abeta) peptides that accumulate in the brain, eventually leading to the neurodegeneration that characterizes Alzheimer’s disease. However, in mice the overexpression of APP gives rise to effects which are not seen in human Alzheimer’s disease.
For example, the APP mutant mice often die of unknown causes at a young age, and the group believes this may be related to the generation of toxic fragments of APP, such as CTF-beta. In addition, some of the fragments of APP could be neuroprotective, making it difficult to judge whether drugs are being effective due to their effect on Abeta peptides, which are known to be involved in human AD, or whether it is due to other effects that would not be seen in human disease. In addition, the gene for expressing APP is inserted in different places in the genome, and may knock out other genes, creating artifacts that are not seen in humans.
With this awareness, more than a decade ago Dr. Saido launched a project to develop a new mouse model that would allow more accurate evaluation of therapies for the disease. One of the major hurdles involved a part of the gene, intron 16, which they discovered was necessary for creating more specific models.
The first mice model they developed (NL-F/NL-F) was knocked in with two mutations found in human familial Alzheimer’s disease. The mice showed early accumulation of Abeta peptides, and importantly, were found to undergo cognitive dysfunction similar to the progression of AD seen in human patients. A second model, with the addition of a further mutation that had been discovered in a family in Sweden, showed even faster initiation of memory loss.
These new models could help in two major areas. The first model, which expresses high levels of the Abeta peptides, seems to realistically model the human form of AD, and could be used for elucidating the mechanism of Abeta deposition. The second model, which demonstrates AD pathology very early on, could be used to examine factors downstream of Abeta-40 and Abeta-42 deposition, such as tauopathy, which are believed to be involved in the neurodegeneration. These results may eventually contribute to drug development and to the discovery of new biomarkers for Alzheimer’s disease. The group is currently looking at several proteins, using the new models, which have potential to be biomarkers.
According to Dr. Saido, “We have a social responsibility to make Alzheimer’s disease preventable and curable. The generation of appropriate mouse models will be a major breakthrough for understanding the mechanism of the disease, which will lead to the establishment of presymptomatic diagnosis, prevention and treatment of the disease.”
Regular aerobic exercise boosts memory area of brain in older women
Regular aerobic exercise seems to boost the size of the area of the brain (hippocampus) involved in verbal memory and learning among women whose intellectual capacity has been affected by age, indicates a small study published online in the British Journal of Sports Medicine.
The hippocampus has become a focus of interest in dementia research because it is the area of the brain involved in verbal memory and learning, but it is very sensitive to the effects of ageing and neurological damage.
The researchers tested the impact of different types of exercise on the hippocampal volume of 86 women who said they had mild memory problems, known as mild cognitive impairment - and a common risk factor for dementia.
All the women were aged between 70 and 80 years old and were living independently at home.
Roughly equal numbers of them were assigned to either twice weekly hour long sessions of aerobic training (brisk walking); or resistance training, such as lunges, squats, and weights; or balance and muscle toning exercises, for a period of six months.
The size of their hippocampus was assessed at the start and the end of the six month period by means of an MRI scan, and their verbal memory and learning capacity was assessed before and afterward using a validated test (RAVLT).
Only 29 of the women had before and after MRI scans, but the results showed that the total volume of the hippocampus in the group who had completed the full six months of aerobic training was significantly larger than that of those who had lasted the course doing balance and muscle toning exercises.
No such difference in hippocampal volume was seen in those doing resistance training compared with the balance and muscle toning group.
However, despite an earlier finding in the same sample of women that aerobic exercise improved verbal memory, there was some evidence to suggest that an increase in hippocampal volume was associated with poorer verbal memory.
This suggests that the relationship between brain volume and cognitive performance is complex, and requires further research, say the authors.
But at the very least, aerobic exercise seems to be able to slow the shrinkage of the hippocampus and maintain the volume in a group of women who are at risk of developing dementia, they say.
And they recommend regular aerobic exercise to stave off mild cognitive decline, which is especially important, given the mounting evidence showing that regular exercise is good for cognitive function and overall brain health, and the rising toll of dementia.
Worldwide, one new case of dementia is diagnosed every four seconds, with the number of those afflicted set to rise to more than 115 million by 2050, they point out.
Older People with Faster Decline In Memory and Thinking Skills May Have Lower Risk of Cancer Death
Older people who are starting to have memory and thinking problems, but do not yet have dementia may have a lower risk of dying from cancer than people who have no memory and thinking problems, according to a study published in the April 9, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Studies have shown that people with Alzheimer’s disease are less likely to develop cancer, but we don’t know the reason for that link,” said study author Julián Benito-León, MD, PhD, of University Hospital 12 of October in Madrid, Spain. “One possibility is that cancer is underdiagnosed in people with dementia, possibly because they are less likely to mention their symptoms or caregivers and doctors are focused on the problems caused by dementia. The current study helps us discount that theory.”
The study involved 2,627 people age 65 and older in Spain who did not have dementia at the start of the study. They took tests of memory and thinking skills at the start of the study and again three years later, and were followed for an average of almost 13 years. The participants were divided into three groups: those whose scores on the thinking tests were declining the fastest, those whose scores improved on the tests, and those in the middle.
During the study, 1,003 of the participants died, including 339 deaths, or 34 percent, among those with the fastest decline in thinking skills and 664 deaths, or 66 percent, among those in the other two groups. A total of 21 percent of those in the group with the fastest decline died of cancer, according to their death certificates, compared to 29 percent of those in the other two groups.
People in the fastest declining group were still 30 percent less likely to die of cancer when the results were adjusted to control for factors such as smoking, diabetes and heart disease, among others.
“We need to understand better the relationship between a disease that causes abnormal cell death and one that causes abnormal cell growth,” Benito-León said. “With the increasing number of people with both dementia and cancer, understanding this association could help us better understand and treat both diseases.”
New research suggests connection between white matter and cognitive health
A multidisciplinary group of scientists from the Sanders-Brown Center on Aging at the University of Kentucky have identified an interesting connection between the health of the brain tissue that supports cognitive functioning and the presence of dementia in adults with Down syndrome.
Published in the Neurobiology of Aging, the study, which focused on detecting changes in the white matter connections of the brain, offers tantalizing potential for the identification of biomarkers connected to the development of dementia, including Alzheimer’s disease.
"We used magnetic resonance imaging to compare the health of the brain’s white matter and how strongly it connects different parts of the brain," explains Elizabeth Head, Ph.D., the study’s senior author. "The results indicate a compelling progression of deterioration in the integrity of white matter in the brains of our study participants commensurate with their cognitive health."
Research team member David Powell, PhD, compared the brain scans of three groups of volunteers: persons with Down syndrome but no dementia, persons with Down syndrome and dementia, and a healthy control group.
Using MRI technologies, brain scans of subjects with Down syndrome showed some compromise in the tissues of brain’s frontal lobe compared to those from the control group. When people with Down syndrome and dementia were compared to people with Down syndrome without dementia, those same white matter connections were even less healthy.
Perhaps the most intriguing aspect of the study was the correlation between the cognitive abilities of participants with Down Syndrome and the integrity of their white matter– those who had higher motor skill coordination and better learning and memory ability had healthier frontal white matter connections.
Persons with Down syndrome are at an extremely high risk for developing Alzheimer’s disease after the age of 40. The team hopes their work might eventually lead to the identification of biomarkers for the development of Alzheimer’s disease in people with Down syndrome and, potentially, extend that to the general population as well.
Head cautions that these results are to some extent exploratory due to the small cohort of 30 participants. But, she says, “If we are able to identify people who, based on biomarkers, have a higher risk of developing Alzheimer’s disease, we might be able to intervene at an earlier point to retard the progression of the disease.”
Green tea is said to have many putative positive effects on health. Now, researchers at the University of Basel are reporting first evidence that green tea extract enhances the cognitive functions, in particular the working memory. The Swiss findings suggest promising clinical implications for the treatment of cognitive impairments in psychiatric disorders such as dementia. The academic journal Psychopharmacology has published their results.
In the past the main ingredients of green tea have been thoroughly studied in cancer research. Recently, scientists have also been inquiring into the beverage’s positive impact on the human brain. Different studies were able to link green tea to beneficial effects on the cognitive performance. However, the neural mechanisms underlying this cognitive enhancing effect of green tea remained unknown.
Better memory
In a new study, the researcher teams of Prof. Christoph Beglinger from the University Hospital of Basel and Prof. Stefan Borgwardt from the Psychiatric University Clinics found that green tea extract increases the brain’s effective connectivity, meaning the causal influence that one brain area exerts over another. This effect on connectivity also led to improvement in actual cognitive performance: Subjects tested significantly better for working memory tasks after the admission of green tea extract.
For the study healthy male volunteers received a soft drink containing several grams of green tea extract before they solved working memory tasks. The scientists then analyzed how this affected the brain activity of the men using magnetic resonance imaging (MRI). The MRI showed increased connectivity between the parietal and the frontal cortex of the brain. These neuronal findings correlated positively with improvement in task performance of the participants. «Our findings suggest that green tea might increase the short-term synaptic plasticity of the brain», says Borgwardt.
Clinical implications
The research results suggest promising clinical implications: Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in neuropsychiatric disorders such as dementia.
High-fat diet in pregnancy linked to Alzheimer’s brain changes in offspring
A new study from scientists in Southampton has suggested that diet during pregnancy may affect an offspring’s risk of brain changes linked to Alzheimer’s disease. The research, which was funded by Alzheimer’s Research UK, studied adult mice whose mothers were fed either a normal or a high-fat diet during pregnancy and lactation. The study is due to be presented at Alzheimer’s Research UK Conference 2014 in Oxford this week.
Led by Dr Cheryl Hawkes at the University of Southampton, the team set out to investigate the links between obesity and Alzheimer’s. Obesity has been linked to a higher risk of the disease, and previous research has suggested that a mother’s diet during pregnancy may affect a child’s risk of obesity and conditions such as heart disease and diabetes in adulthood.
The researchers studied mice which were fed either a standard diet or a high-fat diet, and whose mothers were also fed either a high fat or standard diet during pregnancy and lactation. They then looked at markers of cholesterol and problems with blood vessels in the brain, both of which have been linked to Alzheimer’s.
They found that mice whose mothers ate a high-fat diet during pregnancy were more likely to have vascular changes in their brains later in life. Furthermore, when the offspring of mothers with a high-fat diet were also fed a high-fat diet, their brains’ blood vessels became less efficient at clearing the protein amyloid – a hallmark feature of the disease.
Dr Hawkes, an Alzheimer’s Research UK Senior Research Fellow at the University of Southampton, said: “Our preliminary findings suggest that mothers’ diets during pregnancy may have long-term effects on their children’s brains and vascular health. We still need to do more work to understand how our findings translate to humans, but we have known for some time that protecting mothers’ health during pregnancy can help lower the risk of health problems for their children. Our next step will be to investigate how our findings could relate to Alzheimer’s disease in people. We hope these results could provide a new lead for research to understand how to prevent the disease.”
Alzheimer’s Research UK is the UK’s leading dementia research charity, funding more than £20m of pioneering research into the condition across the UK. The charity’s annual conference on 25 and 26 March is the largest of its kind in the UK, and will see leading dementia scientists share their progress in the drive to defeat dementia.
Dr Eric Karran, Director of Research at Alzheimer’s Research UK, said: “It’s important to remember that this research is in mice, but these results add to existing evidence suggesting that the risk of Alzheimer’s disease in later life is affected by our health earlier in life. This study goes one step further by suggesting that what happens in the womb may also be important. We’re pleased to have funded this research, which has shed new light on the complex picture of Alzheimer’s risk.
“Alzheimer’s is a complicated disease and it’s likely that our risk is affected by a number of different genetic and environmental factors. Research to understand these factors can help equip us to take steps to prevent the disease, but in the meantime, evidence suggests we can lower our risk by eating a healthy, balanced diet, doing regular exercise, not smoking and keeping our blood pressure and weight in check.”
The Aging Brain Needs REST
Why do neurodegenerative diseases such as Alzheimer’s affect only the elderly? Why do some people live to be over 100 with intact cognitive function while others develop dementia decades earlier?
Image: A new study shows that a gene regulator called REST, dormant in the brains of young people (left), switches on in normal aging brains (center) to protect against various stresses, including abnormal proteins associated with neurodegenerative diseases. REST is lost in critical brain regions of people with Alzheimer’s (right). Credit: Yankner Lab
More than a century of research into the causes of dementia has focused on the clumps and tangles of abnormal proteins that appear in the brains of people with neurodegenerative diseases. However, scientists know that at least one piece of the puzzle has been missing because some people with these abnormal protein clumps show few or no signs of cognitive decline.
A new study offers an explanation for these longstanding mysteries. Researchers have discovered that a gene regulator active during fetal brain development, called REST, switches back on later in life to protect aging neurons from various stresses, including the toxic effects of abnormal proteins. The researchers also showed that REST is lost in critical brain regions of people with Alzheimer’s and mild cognitive impairment.
(Source: hms.harvard.edu)
After death, twin brains show similar patterns of neuropathologic changes
Despite widespread use of a single term, Alzheimer’s disease is actually a diverse collection of diseases, symptoms and pathological changes. What’s happening in the brain often varies widely from patient to patient, and a trigger for one person may be harmless is another.
In a unique study, an international team of researchers led by USC psychologist Margaret Gatz compared the brains of twins where one or both died of Alzheimer’s disease. They found that many of the twin pairs not only had similar progressions of Alzheimer’s disease and dementia prior to death, but they also had similar combinations of pathologies — two-or-more unconnected areas of damage to the brain.
The paper is part of Gatz’s landmark body of work on aging and cognition with the Swedish Twin Registry, a large cohort study of more than 14,000 Swedish twins, now over the age of 65. Across nearly 30 years, Gatz’s work with twins — including genetically identical pairs — has shifted the study of Alzheimer’s disease to include the entire lifespan, including the effects of developmental exposure, periodontal disease, mental health, obesity and diabetes on later-life Alzheimer’s risk.
The current paper provides more evidence that there may not be a single smoking-gun cause of Alzheimer’s, but rather a range of potential causes to which we may be susceptible largely depending on our genetics. It appears in the current issue of the journal Brain Pathology.
“We try to make inferences based on tests and diagnoses, but we have to assume that what we’re seeing is a manifestation of what’s going on in these twins’ brains,” said Gatz, professor of psychology, gerontology and preventive medicine in USC Dornsife College. “For this reason, we wanted to compare the brains of twins to ask whether identical twins’ brains are actually more identical?”
The researchers had the rare opportunity to directly autopsy the brains of seven pairs of twins who both died after being receiving diagnostic evaluations over many years, including a pair of identical twins who were both diagnosed with Alzheimer’s and died within a year of one another at the age of 98.
“There may be risk factors that start to accumulate but don’t lead to a clinical diagnosis,” explained lead author Diego Iacono of the Karolinska Institute in Sweden and the Biomedical Research Institute. “We found that the presence of Alzheimer’s disease doesn’t preclude the presence of other damage. Looking at co-pathologies in twin pairs may present new areas for research aside from the typical factors.”
For example, while there’s wide consensus among experts about the course of Alzheimer’s disease and the presence of amyloid plaques and tangles in the brain, what starts the process going is less clear, including the role of lesions, Lewy bodies and vascular or ventricle damage, more often associated with specific types of dementia such as Parkinson’s disease.
“Identical twins tended to have similar combinations of pathologies. We looked not just at the hallmark indicators of Alzheimer’s, but at all the other damage in the brain. Across the whole array of neuropathological changes, the identical twins appeared to have more similar pathologies,” Gatz said. “This is fascinating: it’s not just a key pathology related to the twins’ diagnoses but the combination of things happening in their brains. We’re going to keep looking for what these combinations are.”
(Image: Getty)