'Rejuvenating' the Alzheimer's brain
May 25, 2021
Science Daily/Netherlands Institute for Neuroscience - KNAW
Alzheimer's disease is the main cause of dementia and current therapeutic strategies cannot prevent, slow down or cure the pathology. The disease is characterized by memory loss, caused by the degeneration and death of neuronal cells in several regions of the brain, including the hippocampus, which is where memories are initially formed. Researchers from the Netherlands Institute for Neuroscience (NIN) have identified a small molecule that can be used to rejuvenate the brain and counteract the memory loss.
New cells in old brains
The presence of adult-born cells in the hippocampus of old people was recently demonstrated in scientific studies. It suggests that, generally speaking, the so-called process of adult neurogenesis is sustained throughout adulthood. Adult neurogenesis is linked to several aspects of cognition and memory in both animal models and humans, and it was reported to sharply decrease in the brains of patients with Alzheimer's disease. Researchers also found that higher levels of adult neurogenesis in these patients seem to correlate with better cognitive performance before death. "This could suggest that the adult-born neurons in our brain may contribute to a sort of cognitive reserve that could later on provide higher resilience to memory loss," says Evgenia Salta, group leader at the NIN. Therefore, researchers from the NIN investigated if giving a boost to adult neurogenesis could help prevent or improve dementia in Alzheimer's disease.
A small molecule with big potential
Salta: "Seven years ago, while studying a small RNA molecule that is expressed in our brain, called microRNA-132, we came across a rather unexpected observation. This molecule, which we had previously found to be decreased in the brain of Alzheimer's patients, seemed to regulate homeostasis of neural stem cells in the central nervous system." Back then, Alzheimer's was thought to be a disease affecting only mature neuronal cells, so at first glance this finding did not seem to explain a possible role of microRNA-132 in the progression of Alzheimer's.
In this study, the researchers set out to address whether microRNA-132 can regulate adult hippocampal neurogenesis in healthy and Alzheimer's brains. Using distinct Alzheimer's mouse models, cultured human neural stem cells and post-mortem human brain tissue, they discovered that this RNA molecule is required for the neurogenic process in the adult hippocampus. "Decreasing the levels of microRNA-132 in the adult mouse brain or in human neural stem cells in a dish impairs the generation of new neurons. However, restoring the levels of microRNA-132 in Alzheimer's mice rescues neurogenic deficits and counteracts memory impairment related to adult neurogenesis," Sarah Snoeck, technician in the group of Salta, explains.
These results provide a proof-of-concept regarding the putative therapeutic potential of bringing about adult neurogenesis in Alzheimer's. Salta: "Our next goal is to systematically assess the efficacy and safety of targeting microRNA-132 as a therapeutic strategy in Alzheimer's disease."
https://www.sciencedaily.com/releases/2021/05/210525113701.htm
Press (re)play to remember - How the brain strengthens memories during sleep
May 25, 2021
Science Daily/University of Birmingham
While we sleep, the brain produces particular activation patterns. When two of these patterns -- slow oscillations and sleep spindles -- gear into each other, previous experiences are reactivated. The stronger the reactivation, the clearer will be our recall of past events, a new study reveals.
Scientists have long known that slow oscillations (SOs) and sleep spindles -- sudden half-second to two-second bursts of oscillatory brain activity -- play an important role in the formation and retention of new memories.
But experts in the UK and Germany have discovered that the precise combination of SOs and sleep spindles is vital for opening windows during which memories are reactivated; helping to form and cement memories in the human brain.
Researchers at the University of Birmingham and Ludwig-Maximilians-University Munich today published their findings in Nature Communications.
Co-author Dr Bernhard Staresina, from the University of Birmingham's School of Psychology, commented: "Our main means of strengthening memories while we sleep is the reactivation of previously learnt information, which allows us to solidify memories in neocortical long-term stores.
"We have discovered an intricate interplay of brain activity -- slow oscillations and sleep spindles -- which create windows of opportunity enabling this reactivation."
Co-author Dr Thomas Schreiner, from Ludwig-Maximilians-University, Munich, commented: "Memory reactivation is specifically bound to the presence of SO-spindle complexes. These results shed new light on the memory function of sleep in humans and emphasise the importance of orchestrated sleep rhythms in strengthening our powers of recall and orchestrating the creation of memories."
Before this study, evidence of the brain's capacity to reactivate memories during sleep was scarce, but the team devised novel tests where participants were shown information before taking a nap and closely monitored brain activity during non-rapid eye movement (NREM) sleep using EEG recording. Those taking part were then tested on their memory recall after waking up, allowing the researchers to link the extent of memory reactivation during sleep to memory performance.
The results revealed reactivation of learning material during SO-spindle complexes, with the precision of SO-spindle coupling predicting how strongly the memory would be reactivated by the brain. This in turn predicted the level of memory consolidation across participants and the subsequent clarity of recall.
https://www.sciencedaily.com/releases/2021/05/210525084300.htm
A complex link between body mass index and Alzheimer's
Study finds combined genetic risk, lower BMI predict disease progression
May 19, 2021
Science Daily/Ohio State University
Though obesity in midlife is linked to an increased risk for Alzheimer's disease, new research suggests that a high body mass index later in life doesn't necessarily translate to greater chances of developing the brain disease.
In the study, researchers compared data from two groups of people who had been diagnosed with mild cognitive impairment -- half whose disease progressed to Alzheimer's in 24 months and half whose condition did not worsen.
The researchers zeroed in on two risk factors: body mass index (BMI) and a cluster of genetic variants associated with higher risk for Alzheimer's disease.
Their analysis showed that a higher genetic risk combined with a lower BMI was associated with a higher likelihood for progression to Alzheimer's, and that the association was strongest in men.
The finding does not suggest people should consider gaining weight in their later years as a preventive effort -- instead, researchers speculate that lower BMI in these patients was likely a consequence of neurodegeneration, the progressive damage to the brain that is a hallmark of Alzheimer's. Brain regions affected by Alzheimer's are also involved in controlling eating behaviors and weight regulation.
"We don't want people to think they can eat everything they want because of this lower BMI association," said senior study author Jasmeet Hayes, assistant professor of psychology at The Ohio State University.
"We know that maintaining a healthy weight and having a healthy diet are extremely important to keeping inflammation and oxidative stress down -- that's a risk factor that is modifiable, and it's something you can do to help improve your life and prevent neurodegenerative processes as much as possible," she said. "If you start to notice rapid weight loss in an older individual, that could actually be a reflection of a potential neurodegenerative disease process."
The study was published online recently in the Journals of Gerontology: Series A.
Previous research has found a link between obesity and negative cognitive outcomes, but in older adults closer to the age at which Alzheimer's disease is diagnosed, the results have been mixed, Hayes said. And though a variant to the gene known as APOE4 is the strongest single genetic risk factor for Alzheimer's, it explains only about 10 to 15% of overall risk, she said.
Hayes has focused her research program on looking at multiple risk factors at the same time to see how they might interact to influence risk -- and to identify health behaviors that may help reduce the risk.
"We're trying to add more and more factors. That is my goal, to one day build a more precise and better model of the different combinations of risk factors," said Hayes, also an investigator in Ohio State's Chronic Brain Injury Initiative. "Genetic risk is important, but it really explains only a small part of Alzheimer's disease, so we're really interested in looking at other factors that we can control."
For this study, the research team obtained data from the Alzheimer's Disease Neuroimaging Initiative, compiling a sample of 104 people for whom BMI and polygenic risk scores were available. Fifty-two individuals whose mild cognitive impairment (MCI) had progressed to Alzheimer's in 24 months were matched against demographically similar people whose MCI diagnosis did not change over two years. Their average age was 73.
Statistical analysis showed that individuals with mild cognitive impairment who had both a lower BMI and higher genetic risk for Alzheimer's were more likely to progress to Alzheimer's disease within 24 months compared to people with a higher BMI.
"We think there's interaction between the genetics and lower BMI, and having both of these risk factors causes more degeneration in certain brain regions to increase the likelihood of developing Alzheimer's disease," said Jena Moody, a graduate student in psychology at Ohio State and first author of the paper.
The effect of the BMI-genetic risk interaction was significant even after taking into account the presence of beta-amyloid and tau proteins in the patients' cerebrospinal fluid -- the core biomarkers of Alzheimer's disease.
The relationship between low BMI and high genetic risk and progression to Alzheimer's was stronger in males than in females, but a larger sample size and additional biological data would be needed to expand on that finding, the researchers said.
Because brain changes can begin long before cognitive symptoms surface, a better understanding of the multiple risk factors for Alzheimer's could open the door to better prevention options, Moody said.
"If you can identify people at higher risk before symptoms manifest, you could implement interventions and prevention techniques to either slow or prevent that progression from happening altogether," she said.
To date, scientists have suggested preventive steps include maintaining a healthy weight and diet and participating in activities that reduce inflammation and promote neurofunctioning, such as exercise and mentally stimulating activities.
"We're finding again and again how important inflammation is in the process," Hayes said. "Especially in midlife, trying to keep that inflammation down is such an important aspect of maintaining a healthy lifestyle and preventing accelerated aging."
https://www.sciencedaily.com/releases/2021/05/210519120835.htm
New evidence links gut bacteria and neurodegenerative conditions
May 6, 2021
Science Daily/University of Florida
Neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS affect millions of adults, but scientists still do not know what causes these diseases, which poses a significant roadblock to developing treatments or preventative measures.
Recent research suggests that people with these conditions exhibit changes in the bacterial composition of their digestive tract. However, given the vast diversity of microbes found in the human body, identifying which bacteria may be associated with neurodegeneration is like finding a needle in a haystack.
Seeking that proverbial needle, scientists at the University of Florida are looking in an unexpected place: the digestive tract of a tiny, translucent worm called Caenorhabditis elegans.
New research published in PLOS Pathogens establishes, for the first time, a link between specific bacteria species and physical manifestations of neurodegenerative diseases. The study's lead author is Alyssa Walker, a microbiology and cell science doctoral candidate in the UF/IFAS College of Agricultural and Life Sciences.
"Looking at the microbiome is a relatively new approach to investigating what causes neurodegenerative diseases. In this study, we were able to show that specific species of bacteria play a role in the development of these conditions," said Daniel Czyz, Walker's dissertation advisor.
Czyz is the senior author of the study and an assistant professor in the UF/IFAS department of microbiology and cell science.
"We also showed that some other bacteria produce compounds that counteract these 'bad' bacteria. Recent studies have shown that patients with Parkinson's and Alzheimer's disease are deficient in these 'good' bacteria, so our findings may help explain that connection and open up an area of future study," he added.
All neurodegenerative diseases can be traced to problems with the way proteins are handled in the body. If proteins are misfolded, they build up and accumulate in tissues. These protein aggregates, as scientists call them, interfere with cell functioning and lead to neurodegenerative disorders.
Czyz and his co-authors wanted to know if introducing certain bacteria into the C. elegans worms would be followed by protein aggregation in the worms' tissues.
"That is, in fact, what we observed. We have a way of marking the aggregates so they glow green under the microscope. We saw that worms colonized by certain bacteria species were lit up with aggregates that were toxic to tissues, while those colonized by the control bacteria were not," Czyz said. "This occurred not just in the intestinal tissues, where the bacteria are, but all over the worms' bodies, in their muscles, nerves and even reproductive organs."
Surprisingly, the offspring of affected worms also showed increased protein aggregation -- even though these offspring never encountered the bacteria originally associated with the condition.
"This is very interesting because it suggests that these bacteria generate some sort of a signal that can be passed along to the next generation," Czyz said.
Worms colonized by the "bad" bacteria also lost mobility, a common symptom of neurodegenerative diseases.
"A healthy worm moves around by rolling and thrashing. When you pick up a healthy worm, it will roll off the pick, a simple device that we use to handle these tiny animals. But worms with the bad bacteria couldn't do that because of the appearance of toxic protein aggregates," explained Walker, who developed this assessment method.
"You could compare the pick to an obstacle course: just as a person with a neurodegenerative disease will have trouble getting across, the same is true with these worms, just at a much smaller scale," Czyz added.
Fun fact: Human eyebrow hairs or eyelashes make for very good picks.
"The worms are very delicate, so you need a tool that won't damage them. They are also transparent and have a simple body plan. Studies like ours are possible because these worms normally feed on bacteria," Czyz said.
"The worms are only one millimeter long, and they each have exactly 959 cells," Czyz said. "But in many ways, they are a lot like us humans -- they have intestines and muscles and nerves, but instead of being composed of billions of cells, each organ is just a handful of cells. They are like living test tubes. Their small size allows us to do experiments in a much more controlled way and answer important questions we can apply in future experiments with higher organisms and, eventually, people."
Currently the Czyz lab is testing hundreds of strains of bacteria found in the human gut to see how they affect protein aggregation in C. elegans. The group is also investigating how bacteria associated with neurodegeneration cause protein misfolding at the molecular level.
Czyz is also interested in possible connections between antibiotic-resistant bacteria and protein misfolding.
"Almost all of the bacteria we found associated with protein misfolding are also associated with antibiotic-resistant infections in people. However, it will take many more years of research before we can understand what, if any, connection there is between antibiotic resistance and neurodegenerative diseases," Czyz said.
https://www.sciencedaily.com/releases/2021/05/210506142109.htm
Meditative practice and spiritual wellbeing may preserve cognitive function in aging
May 11, 2021
Science Daily/IOS Press
It is projected that up to 152 million people worldwide will be living with Alzheimer's disease (AD) by 2050. To date there are no drugs that have a substantial positive impact on either the prevention or reversal of cognitive decline. A growing body of evidence finds that targeting lifestyle and vascular risk factors have a beneficial effect on overall cognitive performance. A new review in the Journal of Alzheimer's Disease, published by IOS Press, examines research that finds spiritual fitness, a new concept in medicine that centers on psychological and spiritual wellbeing, and Kirtan Kriya, a simple 12-minute meditative practice, may reduce multiple risk factors for AD.
"The key point of this review is that making a commitment to a brain longevity lifestyle, including spiritual fitness, is a critically important way for aging Alzheimer's disease free," explain authors Dharma Singh Khalsa, MD, Alzheimer's Research and Prevention Foundation, Tucson, AZ, USA, and Andrew B. Newberg, MD, Department of Integrative Medicine and Nutritional Sciences, Department of Radiology, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, USA. "We hope this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability."
Research reveals that religious and spiritual involvement can preserve cognitive function as we age. The authors observe that today, spirituality is often experienced outside the context of an organized religion and may be part of every religion or separate to it. Spiritual fitness is a new dimension in AD prevention, interweaving basic, psychological and spiritual wellbeing. The authors discuss the research on how these factors affect brain function and cognition. For example, psychological wellbeing may reduce inflammation, cardiovascular disease, and disability. Significantly, individuals who have a high score on a "purpose in life" (PIL) measure, a component of psychological wellbeing, were 2.4 times more likely to remain free of AD than individuals with low PIL. In another study, participants who reported higher levels of PIL exhibited better cognitive function, and further, PIL protected those with already existing pathological conditions, thus slowing their decline.
Stress and stress management are under-discussed topics in AD prevention, yet the authors point out that there is ample evidence that physical, psychological, and emotional effects of stress may elevate AD risk. Kirtan Kriya (KK) is a 12-minute singing meditation that involves four sounds, breathing, and repetitive finger movements. It has multiple documented effects on stress, such as improving sleep, decreasing depression, and increasing wellbeing. It has also been found to increase blood flow to areas of the brain involved in cognition and emotional regulation and increases grey matter volume and decreases ventricular size in long-term practitioners, which may slow brain aging. Research in healthy individuals, caregivers, and those with cognitive decline found that the practice improves cognition, slows memory loss, and improves mood.
The overall relationship between spiritual fitness and a person's complete physical and mental health is a topic of investigation in the emerging field of study called neurotheology. Early work has focused on the development of models regarding which brain areas are affected through spiritual practices such as meditation or prayer. Over the last 20 years, there has been an extensive growth in neuroimaging and other physiological studies evaluating the effect of meditation, spiritual practices, and mystical experiences. A neuroimaging study of KK found long term brain effects, during meditation and afterwards. Neurotheological studies can help understanding of how a practice such as KK can lead to more permanent effects in brain function that support spiritual fitness, according to Dr. Khalsa and Dr. Newberg.
"Mitigating the extensive negative biochemical effects of stress with meditation practices, in tandem with the creation of heightened levels of spiritual fitness, may help lower the risk of AD. Small shifts in one's daily routine can make all the difference in AD prevention," Dr. Khalsa and Dr. Newberg conclude. "We are optimistic this article will inspire future research on the topic of spiritual fitness and AD."
https://www.sciencedaily.com/releases/2021/05/210511123727.htm
Alzheimer's study: A Mediterranean diet might protect against memory loss and dementia
May 6, 2021
Science Daily/DZNE - German Center for Neurodegenerative Diseases
In Alzheimer's disease, neurons in the brain die. Largely responsible for the death of neurons are certain protein deposits in the brains of affected individuals: So-called beta-amyloid proteins, which form clumps (plaques) between neurons, and tau proteins, which stick together the inside of neurons. The causes of these deposits are as yet unclear. In addition, a rapidly progressive atrophy, i.e. a shrinking of the brain volume, can be observed in affected persons. Alzheimer's symptoms such as memory loss, disorientation, agitation and challenging behavior are the consequences.
Scientists at the DZNE led by Prof. Michael Wagner, head of a research group at the DZNE and senior psychologist at the memory clinic of the University Hospital Bonn, have now found in a study that a regular Mediterranean-like dietary pattern with relatively more intake of vegetables, legumes, fruit, cereals, fish and monounsaturated fatty acids, such as from olive oil, may protect against protein deposits in the brain and brain atrophy. This diet has a low intake of dairy products, red meat and saturated fatty acids.
A total of 512 subjects with an average age of around seventy years took part in the study. 169 of them were cognitively healthy, while 343 were identified as having a higher risk of developing Alzheimer's disease -- due to subjective memory impairment, mild cognitive impairment that is the precursor to dementia, or first-degree relationship with patients diagnosed with Alzheimer's disease. The nutrition study was funded by the Diet-Body-Brain competence cluster of the German Federal Ministry of Education and Research (BMBF) and took place as part of the so-called DELCODE study of the DZNE, which does nationwide research on the early phase of Alzheimer's disease -- that period before pronounced symptoms appear.
"People in the second half of life have constant eating habits. We analyzed whether the study participants regularly eat a Mediterranean diet -- and whether this might have an impact on brain health ," said Prof. Michael Wagner. The participants first filled out a questionnaire in which they indicated which portions of 148 different foods they had eaten in the past months. Those who frequently ate healthy foods typical of the Mediterranean diet, such as fish, vegetables and fruit, and only occasionally consumed foods such as red meat, scored highly on a scale.
An extensive test series
The scientists then investigated brain atrophy: they performed brain scans with magnetic resonance imaging (MRI) scanners to determine brain volume. In addition, all subjects underwent various neuropsychological tests in which cognitive abilities such as memory functions were examined. The research team also looked at biomarker levels (measured values) for amyloid beta proteins and tau proteins in the so-called cerebrospinal fluid (CSF) of 226 subjects.
The researchers, led by Michael Wagner, found that those who ate an unhealthy diet had more pathological levels of these biomarkers in the cerebrospinal fluid than those who regularly ate a Mediterranean-like diet. In the memory tests, the participants who did not adhere to the Mediterranean diet also performed worse than those who regularly ate fish and vegetables. "There was also a significant positive correlation between a closer adherence to a Mediterranean-like diet and a higher volume of the hippocampus. The hippocampus is an area of the brain that is considered the control center of memory. It shrinks early and severely in Alzheimer's disease," explained Tommaso Ballarini, PhD, postdoctoral fellow in Michael Wagner's research group and lead author of the study.
Continuation of nutrition study is planned
"It is possible that the Mediterranean diet protects the brain from protein deposits and brain atrophy that can cause memory loss and dementia. Our study hints at this," Ballarini said. "But the biological mechanism underlying this will have to be clarified in future studies." As a next step, Ballarini and Wagner now plan to re-examine the same study participants in four to five years to explore how their nutrition -- Mediterranean-like or unhealthy -- affects brain aging over time.
https://www.sciencedaily.com/releases/2021/05/210506105355.htm
Your neighborhood may affect your brain health
Study finds evidence of more brain aging in people living in disadvantaged areas
April 19, 2021
Science Daily/American Academy of Neurology
Middle-age and older people living in more disadvantaged neighborhoods -- areas with higher poverty levels and fewer educational and employment opportunities -- had more brain shrinkage on brain scans and showed faster decline on cognitive tests than people living in neighborhoods with fewer disadvantages, according to a study published in the April 14, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology. Researchers say such brain aging may be a sign of the earliest stages of dementia.
"Worldwide, dementia is a major cause of illness and a devastating diagnosis," said study author Amy J. H. Kind M.D., Ph.D., of the University of Wisconsin School of Medicine and Public Health in Madison. "There are currently no treatments to cure the disease, so identifying possible modifiable risk factors is important. Compelling evidence exists that the social, economic, cultural and physical conditions in which humans live may affect health. We wanted to determine if these neighborhood conditions increase the risk for the neurodegeneration and cognitive decline associated with the earliest stages of Alzheimer's disease and dementia."
For the study, researchers identified 601 people from two larger studies of Wisconsin residents. Participants had an average age of 59 and no thinking or memory problems at the start of the study, although 69% had a family history of dementia. They were followed for 10 years.
Participants had an initial MRI brain scan and then additional scans every three to five years. With each scan, researchers measured brain volume in areas of the brain linked to the development of Alzheimer's dementia. Participants also took thinking and memory tests every two years, including tests that measured processing speed, mental flexibility and executive function.
Researchers used the residential address of each participant and a measure called the Area Deprivation Index to determine if each participant lived in an advantaged or disadvantaged neighborhood. Neighborhoods in the index are determined by census areas of 1,500 residents. The index incorporates information on the socioeconomic conditions of each neighborhood and its residents, ranking neighborhoods based on 17 indicators including income, employment, education and housing quality.
Of all participants, 19 people lived in the 20% most disadvantaged neighborhoods in their state and 582 people lived in the 80% of all other neighborhoods in their state. People in the first group were then matched one to four to people in the second group for race, sex, age and education and compared.
At the start of the study, there was no difference in brain volume between people living in the most disadvantaged neighborhoods and those in other neighborhoods. But at the end, researchers found brain shrinkage in areas of the brain associated with dementia in people in the most disadvantaged neighborhoods, while there was no shrinkage in the other group. Researchers also found a higher rate of decline on tests that measure risk of Alzheimer's disease.
"Our findings suggest that increased vigilance by healthcare providers for early signs of dementia may be particularly important in this vulnerable population," said Kind. "Some possible causes of these brain changes may include air pollution, lack of access to healthy food and healthcare and stressful life events. Further research into possible social and biological pathways may help physicians, researchers and policymakers identify effective avenues for prevention and intervention in Alzheimer's disease and related dementia."
Limitations of the study included a small number of participants from highly disadvantaged neighborhoods and a limited geographic setting. Future studies should involve larger and more diverse groups of people over longer periods of time.
https://www.sciencedaily.com/releases/2021/04/210419110148.htm
Exercise boosts blood flow to the brain
The results add to growing evidence that exercise programs may help older adults slow the onset of memory loss and dementia
March 23, 2021
Science Daily/UT Southwestern Medical Center
It's not just your legs and heart that get a workout when you walk briskly; exercise affects your brain as well. A new study by researchers at UT Southwestern shows that when older adults with mild memory loss followed an exercise program for a year, the blood flow to their brains increased. The results were published online today in the Journal of Alzheimer's Disease.
"This is part of a growing body of evidence linking exercise with brain health," says study leader Rong Zhang, Ph.D., professor of neurology at UTSW. "We've shown for the first time in a randomized trial in these older adults that exercise gets more blood flowing to your brain."
As many as one-fifth of people age 65 and older have some level of mild cognitive impairment (MCI) -- slight changes to the brain that affect memory, decision-making, or reasoning skills. In many cases, MCI progresses to dementia, including Alzheimer's disease.
Scientists have previously shown that lower-than-usual levels of blood flow to the brain, and stiffer blood vessels leading to the brain, are associated with MCI and dementia. Studies have also suggested that regular aerobic exercise may help improve cognition and memory in healthy older adults. However, scientists have not established whether there is a direct link between exercise, stiffer blood vessels, and brain blood flow.
"There is still a lot we don't know about the effects of exercise on cognitive decline later in life," says C. Munro Cullum, Ph.D., professor of psychiatry at UTSW and co-senior author of the study. "MCI and dementia are likely to be influenced by a complex interplay of many factors, and we think that, at least for some people, exercise is one of those factors."
In the study, Zhang, Cullum, and their colleagues followed 70 men and women aged 55 to 80 who had been diagnosed with MCI. Participants underwent cognitive exams, fitness tests, and brain magnetic resonance imaging (MRI) scans. Then they were randomly assigned to either follow a moderate aerobic exercise program or a stretching program for one year. The exercise program involved three to five exercise sessions a week, each with 30-40 minutes of moderate exercise such as a brisk walk.
In both programs, exercise physiologists supervised participants for the first four to six weeks, then had the patients record their exercises and wear a heart rate monitor during exercise.
Forty-eight study participants -- 29 in the stretching group and 19 in the aerobic exercise group -- completed the full year of training and returned for follow-up tests. Among them, those who performed aerobic exercise showed decreased stiffness of blood vessels in their neck and increased overall blood flow to the brain. The more their oxygen consumption (one marker of aerobic fitness) increased, the greater the changes to the blood vessel stiffness and brain blood flow. Changes in these measurements were not found among people who followed the stretching program.
While the study didn't find any significant changes in memory or other cognitive function, the researchers say that may be because of the small size or short length of the trial. Changes to blood flow could precede changes to cognition, they say. They're already carrying out a larger two-year study, Risk Reduction for Alzheimer's Disease (rrAD), that further investigates the link between exercise and cognitive decline.
"There are likely some people who benefit more from exercise than others," says Cullum. "But with the sample size in this study, it was hard to analyze subgroups of people to make those conclusions."
Still, the data are important to help explain the effects of exercise on the brain and why it can be beneficial, say Zhang and Cullum, who are members of the Peter O'Donnell Jr. Brain Institute.
"Having physiological findings like this can also be useful for physicians when they talk to their patients about the benefits of exercise," says Zhang. "We now know, based on a randomized, controlled trial, that exercise can increase blood flow to the brain, which is a good thing."
https://www.sciencedaily.com/releases/2021/03/210323131213.htm
Aluminum is intricately associated with the neuropathology of familial Alzheimer's disease
April 9, 2021
Science Daily/IOS Press
A new study published in the Journal of Alzheimer's Disease Reports continues to support a growing body of evidence that aluminum contributes to the pathogenesis of Alzheimer's disease (AD). Researchers found aluminum co-located with phosphorylated tau protein, which is an early initiator of AD. This study builds upon two earlier published studies (including Mold et al., 2020, Journal of Alzheimer's Disease) from the same group.
The new data demonstrate that aluminum is co-located with phosphorylated tau protein, present as tangles within neurons in the brains of early-onset or familial Alzheimer's disease. "The presence of these tangles is associated with neuronal cell death, and observations of aluminum in these tangles may highlight a role for aluminum in their formation," explained lead investigator Matthew John Mold, PhD, Birchall Centre, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.
The earlier research highlighted widespread co-localization of aluminum and amyloid-β in brain tissue in familial AD. The researchers used a highly-selective method of immunolabelling in the current study, combined with aluminum-specific fluorescence microscopy. Phosphorylated tau in tangles co-located with aluminum in the brain tissue of the same cohort of Colombian donors with familial AD were identified. "It is of interest and perhaps significance with respect to aluminum's role in AD that its unequivocal association with tau is not as easily recognizable as with amyloid-β. There are many more aggregates of aluminum with amyloid-β than with tau in these tissues and the latter are predominantly intracellular," remarked co-author, Professor Christopher Exley.
George Perry, PhD, Editor-in-Chief of the Journal of Alzheimer's Disease, comments: "Aluminum accumulation has been associated with Alzheimer's disease for nearly half a century, but it is the meticulously specific studies of Drs. Mold and Exley that are defining the exact molecular interaction of aluminum and other multivalent metals that may be critical to formation of the pathology of Alzheimer's disease."
"The new data may suggest that the association of aluminum with extracellular senile plaques precedes that with intracellular aggregates of tau. These relationships with both amyloid-β and tau may account for the high levels of aluminum observed in the brain tissue of donors with familial AD versus those without a diagnosis of neurodegenerative disease," said Dr. Mold. "Tau and amyloid-beta are known to act in synergy to produce neurotoxicity in AD and our data provide new evidence for a role of aluminum in this process."
https://www.sciencedaily.com/releases/2021/04/210409124748.htm
Fighting dementia with play
April 9, 2021
Science Daily/ETH Zurich
A dementia diagnosis turns the world upside down, not only for the person affected but also for their relatives, as brain function gradually declines. Those affected lose their ability to plan, remember things or behave appropriately. At the same time, their motor skills also deteriorate. Ultimately, dementia patients are no longer able to handle daily life alone and need comprehensive care. In Switzerland alone, more than 150,000 people share this fate, and each year a further 30,000 new cases are diagnosed.
To date, all attempts to find a drug to cure this disease have failed. Dementia, including Alzheimer's -- the most common of several forms of dementia -- remains incurable. However, a clinical study carried out in Belgium with the involvement of ETH researcher Eling de Bruin has now shown for the first time that cognitive motor training improves both the cognitive and physical skills of significantly impaired dementia patients. A fitness game, known as "Exergame," developed by the ETH spin-off Dividat was used in the study.
Better cognitive ability thanks to training
In 2015, a team of scientists led by ETH researcher Patrick Eggenberger showed that older people who train both body and mind simultaneously demonstrate better cognitive performance and can thereby also prevent cognitive impairment (as reported by ETH News). However, this study was carried out on healthy subjects only.
"It has been suspected for some time that physical and cognitive training also have a positive effect on dementia," explains de Bruin, who worked with Eggenberger at the Institute of Human Movement Sciences and Sport at ETH Zurich. "However, in the past it has been difficult to motivate dementia patients to undertake physical activity over extended periods."
ETH spin-off combines exercise and fun
With a view to changing this, Eva van het Reve, a former ETH doctoral student, founded the ETH spin-off Dividat in 2013 together with her PhD supervisor Eling de Bruin and another doctoral student. "We wanted to devise a customised training programme that would improve the lives of older people," says van het Reve. Fun exercises were developed in order to encourage people who were already experiencing physical and cognitive impairments to participate in training, and the Senso training platform was born.
The platform consists of a screen with the game software and a floor panel with four fields that measure steps, weight displacement and balance. The users attempt to complete a sequence of movements with their feet as indicated on the screen, enabling them to train both physical movement and cognitive function simultaneously. The fact that the fitness game is also fun makes it easier to motivate the subjects to practice regularly.
Eight weeks' training for dementia patients
An international team led by Nathalie Swinnen, a doctoral student at KU Leuven, and co-supervised by ETH researcher de Bruin, recruited 45 subjects for the study. The subjects were residents of two Belgian care homes, aged 85 years on average at the time of the study and all with severe dementia symptoms.
"The participants were divided into two groups on a random basis," explains de Bruin. "The first group trained for 15 minutes with the Dividat Senso three times a week for eight weeks, while the second group listened to and watched music videos of their choice." Following the eight-week training programme, the physical, cognitive and mental capacity of all subjects was measured in comparison with the start of the study.
Regular play has an effect
The results offer hope to dementia patients and their relatives: training with this machine indeed enhanced cognitive skills, such as attention, concentration, memory and orientation. "For the first time, there's hope that through targeted play we will be able not only to delay but also weaken the symptoms of dementia," emphasises de Bruin.
It is particularly striking that the control group deteriorated further over the eight-week period, while significant improvements were recorded in the training group. "These highly encouraging results are in line with the expectation that dementia patients are more likely to deteriorate without training," adds de Bruin.
But playful training not only has a positive impact on cognitive ability -- researchers were also able to measure positive effects on physical capability, such as reaction time. After just eight weeks, the subjects in the training group reacted significantly more quickly, while the control group deteriorated. This is encouraging in that the speed with which older people respond to impulses is critical in determining whether they can to avoid a fall.
A better understanding of brain processes
The research group led by de Bruin is currently working on replicating the results of this pilot study with people with mild cognitive impairment -- a precursor of dementia. The aim is to use MRI scans to investigate more closely the neural processes in the brain responsible for the cognitive and physical improvement.
https://www.sciencedaily.com/releases/2021/04/210409093607.htm