Absentmindedness points to earlier warning signs of silent strokes among people at risk

February 6, 2019

Science Daily/Baycrest Centre for Geriatric Care

Adults who notice that they frequently lose their train of thought or often become sidetracked may in fact be displaying earlier symptoms of cerebral small vessel disease, otherwise known as a 'silent stroke,' suggests a recent study.

Researchers uncovered that individuals with damage to the brain's white matter, caused by silent strokes, reported poor attentiveness and being distracted more frequently on day-to-day tasks, according to a recently published paper in the journal Neurobiology of Aging. Despite these complaints, about half of the people with identified white matter damage scored within the normal range on formal laboratory assessments of attention and executive function (a person's ability to plan, stay organized and maintain focus on overall goals).

"Our results indicate that in many cases of people who were at a higher risk of silent stroke and had one, they saw a notable difference in their ability to stay focused, even before symptoms became detectable through a neuropsychological test," says Ayan Dey, lead author on the paper and a graduate student at Baycrest's Rotman Research Institute (RRI) and the University of Toronto. "If a person feels this may be the case, concerns should be brought to a doctor, especially if the person has a health condition or lifestyle that puts them at a higher risk of stroke or heart disease."

Cerebral small vessel disease is one of the most common neurological disorders of aging. This type of stroke and changes in the brain's blood flow (vascular changes) are connected to the development of vascular dementia and a higher risk of Alzheimer's disease and other dementias.

The strokes are "silent" since they don't cause lasting major changes seen with an overt stroke, such as affecting a person's ability to speak or paralysis. Despite a lack of obvious symptoms, cerebral small vessel disease causes damage to the brain's white matter (responsible for communication among regions), which can cause memory and cognitive issues over time.

Typically, this type of stroke is uncovered incidentally through MRI scans or once the brain damage has worsened, says Dey.

"There are no effective treatments for Alzheimer's disease, but brain vascular changes can be prevented or reduced through smoking cessation, exercise, diet and stress management, as well as keeping one's blood pressure, diabetes and cholesterol under control," says Dr. Brian Levine, senior author on the paper, RRI senior scientist and professor of Psychology and Neurology at the University of Toronto. "With the right diagnosis, these interventions and lifestyle changes give older adults who are at risk for cognitive decline some options for maintaining brain health."

The study looked at results from 54 adults (between the ages of 55 to 80), who also possessed at least one risk factor for a stroke, such as high blood pressure, high cholesterol, diabetes, sleep apnea, a history of smoking, past mini strokes and advanced age above 75.

Research participants had their brains scanned by MRI and scientists analyzed brain tissue damage, specifically in relation to white matter, to determine injuries caused by cerebral small vessel disease. They also took part in a number of neurocognitive tests and questionnaires that assessed their attention and executive function.

Following up on this study, researchers will analyze functional brain imaging and electrical brain activity from participants to look at the differences in brain networks. They hope to uncover why some people are still able to perform well on cognitive assessments, despite damage to the brain.

"The question that remains is whether overcoming these changes in the brain is a natural ability some people have or if this is something that can be built up over time," says Dey. "If it's something that can be developed, is it something we can train?"

https://www.sciencedaily.com/releases/2019/02/190206091417.htm

A new culprit in cognitive decline in Alzheimer's disease

Study finds blood protein destroys memory storage sites in the brain and may lead to new treatments

February 5, 2019

Science Daily/Gladstone Institutes

Scientists have shown for the first time that a blood-clotting protein called fibrinogen is responsible for a series of molecular and cellular events that can destroy connections between neurons in the brain and result in cognitive decline.

It has long been known that patients with Alzheimer's disease have abnormalities in the vast network of blood vessels in the brain. Some of these alterations may also contribute to age-related cognitive decline in people without dementia. However, the ways in which such vascular pathologies contribute to cognitive dysfunction have largely remained a mystery. Until now, that is.

Scientists at the Gladstone Institutes, led by Senior Investigator Katerina Akassoglou, PhD, showed for the first time that a blood-clotting protein called fibrinogen is responsible for a series of molecular and cellular events that can destroy connections between neurons in the brain and result in cognitive decline.

Akassoglou and her team used state-of-the-art imaging technology to study both mouse brains and human brains from patients with Alzheimer's disease. They also produced the first three-dimensional volume imaging showing that blood-brain barrier leaks occur in Alzheimer's disease.

In their study, published in the scientific journal Neuron, the researchers found that fibrinogen, after leaking from the blood into the brain, activates the brain's immune cells and triggers them to destroy important connections between neurons. These connections, called synapses, are critical for neurons to communicate with one another.

Previous studies have shown that elimination of synapses causes memory loss, a common feature in Alzheimer's disease and other dementias. Indeed, the scientists showed that preventing fibrinogen from activating the brain's immune cells protected mouse models of Alzheimer's disease from memory loss.

"We found that blood leaks in the brain can cause elimination of neuronal connections that are important for memory functions," explains Akassoglou, who is also a professor of neurology at UC San Francisco (UCSF). "This could change the way we think about the cause and possible cure of cognitive decline in Alzheimer's disease and other neurological diseases."

The team showed that fibrinogen can have this effect even in brains that lack amyloid plaques, which are the focus of diverse treatment strategies that have failed in large clinical trials. The researchers showed that injecting even extremely small quantities of fibrinogen into a healthy brain caused the same kind of immune cell activation and loss of synapses they saw in Alzheimer's disease.

"Traditionally, the build-up of amyloid plaques in the brain has been seen as the root of memory loss and cognitive decline in Alzheimer's disease," says Mario Merlini, first author of the study and a staff research scientist in Akassoglou's laboratory at Gladstone. "Our work identifies an alternative culprit that could be responsible for the destruction of synapses."

The scientists' data help explain findings from recent human studies in which elderly people with vascular pathology showed similar rates of cognitive decline as age-matched people with amyloid pathology. However, patients with both types of pathology had much worse and more rapid cognitive decline. Other studies also identified vascular pathology as a strong predictor of cognitive decline that can act independently of amyloid pathology.

"Given the human data showing that vascular changes are early and additive to amyloid, a conclusion from those studies is that vascular changes may have to be targeted with separate therapies if we want to ensure maximum protection against the destruction of neuronal connections that leads to cognitive decline," says Akassoglou.

Interestingly, Akassoglou and her colleagues recently developed an antibody that blocks the interaction between fibrinogen and a molecule on the brain's immune cells. In a previous study, they showed this antibody protected mouse models of Alzheimer's disease from brain inflammation and neuronal damage.

"These exciting findings greatly advance our understanding of the contributions that vascular pathology and brain inflammation make to the progression of Alzheimer's disease," said Lennart Mucke, MD, co-author of the study and director of the Gladstone Institute of Neurological Disease. "The mechanisms our study identified may also be at work in a range of other diseases that combine leaks in the blood-brain barrier with neurological decline, including multiple sclerosis, traumatic brain injury, and chronic traumatic encephalopathy. It has far-reaching therapeutic implications."

https://www.sciencedaily.com/releases/2019/02/190205115419.htm

Scientists shed light on processes behind age-related decline in brain structures

January 31, 2019

Science Daily/Cardiff University

Aging can cause damage to support cells in the white matter, which in turn may lead to damage in the grey matter of the hippocampus, finds a new study.

The discovery gives researchers a new area to focus on in the search for treatments that can protect cognitive function.

Claudia Metzler-Baddeley, from Cardiff University's Brain Imaging Research Centre (CUBRIC), said: "The brain is made up of grey and white matter. While grey matter contains neuronal cells, which perform computations in our brain, the white matter contains connections and support cells that help the communication between different areas.

"Our new study not only confirms that aging leads to both grey matter decline in the hippocampus and white matter decline in the surrounding area, but also reveals the causal relationship between the two.

"Using a method called mediation analysis, we discovered that ageing of the white matter was accounting for ageing of hippocampal grey matter and not the other way around. Our results suggest that damage to the support cells may affect tissue health in the hippocampus, a region important for memory and involved in Alzheimer's disease.

"This is an exciting find. If hard-working support cells in the white matter start to misfunction with age, then therapies that protect these support cells may aid in the fight against the damage that ageing can do to our cognitive ability."

The study, which looked at the brains of 166 healthy volunteers, was carried out using state-of-the-art brain imaging techniques at CUBRIC and was jointly funded by the Alzheimer's Society and the BRACE Alzheimer's charity.

https://www.sciencedaily.com/releases/2019/01/190131104936.htm

Lowering blood pressure reduces risk of cognitive impairment

January 28, 2019

Science Daily/Wake Forest Baptist Medical Center

Intensive control of blood pressure in older people significantly reduced the risk of developing mild cognitive impairment (MCI), a precursor of early dementia, in a clinical trial led by scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health. However, the National Institutes of Health-supported Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND) study did not prove that treating blood pressure to a goal of 120 mm Hg or less statistically reduced the risk of dementia. This result may have been due to too few new cases of dementia occurring in the study, the authors noted.

The results were reported in the Jan. 28 edition of the Journal of the American Medical Association.

MCI is defined as a decline in memory and thinking skills that is greater than expected with normal aging and is a risk factor for dementia. Dementia is defined as a group of symptoms associated with a decline in memory or other thinking skills severe enough to reduce a person's ability to perform everyday activities.

"As doctors treating older patients, we are encouraged to finally have a proven intervention to lower someone's risk for MCI," said the study's principal investigator, Jeff Williamson, M.D., professor of gerontology and geriatric medicine at Wake Forest School of Medicine. "In the study, we found that just three years of lowering blood pressure not only dramatically helped the heart but also helped the brain."

The objective of SPRINT MIND was to evaluate the effect of intensive blood pressure control on risk of dementia. Hypertension, which affects more than half of people over age 50 and more than 75 percent of those older than 65, has been identified as a potentially modifiable risk factor for MCI and dementia in previous observational studies.

The clinical trial, which enrolled 9361 volunteers, was conducted at 102 sites in the United States and Puerto Rico among adults 50 and older with hypertension but without diabetes or history of stroke. The participating group was 35.6 percent female, 30 percent black and 10.5 percent Hispanic and thus representative of the broader U.S. population.

Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm HG (intensive treatment) or less than 140 mm HG (standard treatment). They were then classified after five years as having no cognitive impairment, MCI or probable dementia.

"Although the study showed a 15 percent reduction in dementia in the intensively controlled group, we were disappointed that the results did not achieve statistical significance for this outcome," Williamson said. "Last week the Alzheimer's Association agreed to fund additional follow-up of SPRINT MIND participants in the hope that sufficient dementia cases will accrue, allowing for a more definitive statement on these outcomes."

SPRINT was stopped early due to the success of the trial in reducing cardiovascular disease. As a result, participants were on intensive blood pressure lowering treatment for a shorter period than originally planned. The authors concluded that the shorter time may have made it difficult to accurately determine the role of intensive blood pressure control on dementia cases.

Williamson said some caution should be exercised in interpreting the study result both because MCI was not the primary cognitive focus of the trial and because it is not clear what intensive blood pressure control may mean for the longer-term incidence of dementia. Although MCI considerably increases the risk of dementia, this progression is not inevitable and reversion to normal cognition is possible, he said.

https://www.sciencedaily.com/releases/2019/01/190128111703.htm

Physical activity keeps hippocampus healthy those at risk for Alzheimer's disease

April 23, 2014

Science Daily/University of Maryland

A study of older adults at increased risk for Alzheimer's disease shows that moderate physical activity may protect brain health and stave off shrinkage of the hippocampus- the brain region responsible for memory and spatial orientation that is attacked first in Alzheimer's disease. Dr. J. Carson Smith, a kinesiology researcher in the University of Maryland School of Public Health who conducted the study, says that while all of us will lose some brain volume as we age, those with an increased genetic risk for Alzheimer's disease typically show greater hippocampal atrophy over time. The findings are published in the open-access journal Frontiers in Aging Neuroscience.

"The good news is that being physically active may offer protection from the neurodegeneration associated with genetic risk for Alzheimer's disease," Dr. Smith suggests. "We found that physical activity has the potential to preserve the volume of the hippocampus in those with increased risk for Alzheimer's disease, which means we can possibly delay cognitive decline and the onset of dementia symptoms in these individuals. Physical activity interventions may be especially potent and important for this group."

Dr. Smith and colleagues, including Dr. Stephen Rao from the Cleveland Clinic, tracked four groups of healthy older adults ages 65-89, who had normal cognitive abilities, over an 18-month period and measured the volume of their hippocampus (using structural magnetic resonance imaging, or MRI) at the beginning and end of that time period. The groups were classified both for low or high Alzheimer's risk (based on the absence or presence of the apolipoprotein E epsilon 4 allele) and for low or high physical activity levels.

Of all four groups studied, only those at high genetic risk for Alzheimer's who did not exercise experienced a decrease in hippocampal volume (3%) over the 18-month period. All other groups, including those at high risk for Alzheimer's but who were physically active, maintained the volume of their hippocampus.

"This is the first study to look at how physical activity may impact the loss of hippocampal volume in people at genetic risk for Alzheimer's disease," says Dr. Kirk Erickson, an associate professor of psychology at the University of Pittsburgh. "There are no other treatments shown to preserve hippocampal volume in those that may develop Alzheimer's disease. This study has tremendous implications for how we may intervene, prior to the development of any dementia symptoms, in older adults who are at increased genetic risk for Alzheimer's disease."

Individuals were classified as high risk for Alzheimer's if a DNA test identified the presence of a genetic marker -- having one or both of the apolipoprotein E-epsilon 4 allele (APOE-e4 allele) on chromosome 19 -- which increases the risk of developing the disease. Physical activity levels were measured using a standardized survey, with low activity being two or fewer days/week of low intensity activity, and high activity being three or more days/week of moderate to vigorous activity.

"We know that the majority of people who carry the APOE-e4 allele will show substantial cognitive decline with age and may develop Alzheimer's disease, but many will not. So, there is reason to believe that there are other genetic and lifestyle factors at work," Dr. Smith says. "Our study provides additional evidence that exercise plays a protective role against cognitive decline and suggests the need for future research to investigate how physical activity may interact with genetics and decrease Alzheimer's risk."

Dr. Smith has previously shown that a walking exercise intervention for patients with mild cognitive decline improved cognitive function by improving the efficiency of brain activity associated with memory. He is planning to conduct a prescribed exercise intervention in a population of healthy older adults with genetic and other risk factors for Alzheimer's disease and to measure the impact on hippocampal volume and brain function.

http://www.sciencedaily.com/releases/2014/04/140423102746.htm

Eating fish reduces risk of Alzheimer's disease

December 1, 2011

Science Daily/Radiological Society of North America

People who eat baked or broiled fish on a weekly basis may be improving their brain health and reducing their risk of developing mild cognitive impairment and Alzheimer's disease, according to a new study.

"This is the first study to establish a direct relationship between fish consumption, brain structure and Alzheimer's risk," said Cyrus Raji, M.D., Ph.D., from the University of Pittsburgh Medical Center and the University of Pittsburgh School of Medicine. "The results showed that people who consumed baked or broiled fish at least one time per week had better preservation of gray matter volume on MRI in brain areas at risk for Alzheimer's disease."

Alzheimer's disease is an incurable, progressive brain disease that slowly destroys memory and cognitive skills. According to the National Institute on Aging, as many as 5.1 million Americans may have Alzheimer's disease. In MCI, memory loss is present but to a lesser extent than in Alzheimer's disease. People with MCI often go on to develop Alzheimer's disease.

The findings showed that consumption of baked or broiled fish on a weekly basis was positively associated with gray matter volumes in several areas of the brain. Greater hippocampal, posterior cingulate and orbital frontal cortex volumes in relation to fish consumption reduced the risk for five-year decline to MCI or Alzheimer's by almost five-fold.

"Consuming baked or broiled fish promotes stronger neurons in the brain's gray matter by making them larger and healthier," Dr. Raji said. "This simple lifestyle choice increases the brain's resistance to Alzheimer's disease and lowers risk for the disorder." The results also demonstrated increased levels of cognition in people who ate baked or broiled fish.

"Working memory, which allows people to focus on tasks and commit information to short-term memory, is one of the most important cognitive domains," Dr. Raji said. "Working memory is destroyed by Alzheimer's disease. We found higher levels of working memory in people who ate baked or broiled fish on a weekly basis, even when accounting for other factors, such as education, age, gender and physical activity." Eating fried fish, on the other hand, was not shown to increase brain volume or protect against cognitive decline.

http://www.sciencedaily.com/releases/2011/11/111130095257.htm

Common irregular heartbeat raises risk of dementia

August 30, 2011

Science Daily/Group Health Research Institute

The most common kind of chronically irregular heartbeat, known as atrial fibrillation, is associated with a greater risk of dementia, including Alzheimer's disease, according to a new study.

"Both atrial fibrillation and dementia increase with age," said Sascha Dublin, MD, PhD, a Group Health Research Institute assistant investigator who led the research. "Before our prospective cohort study, we knew that atrial fibrillation can cause stroke, which can lead to dementia. Now we've learned that atrial fibrillation may increase dementia risk in other, more subtle ways as well."

The results of Dr. Dublin's study suggest a relationship between atrial fibrillation and dementia beyond the connection through stroke. The people in the study had a mean age of 74 years when the study began. None had dementia or a history of stroke. At the beginning of the study, 4.3 percent had atrial fibrillation, and an additional 12.2 percent developed it during the study.

In the course of the study, 18.8 percent developed some type of dementia. People with atrial fibrillation were more likely to have other cardiovascular risk factors and disease than were those without the condition. So the researchers looked to see if atrial fibrillation increased dementia risk more than just through its association with other kinds of heart disease.

http://www.sciencedaily.com/releases/2011/08/110808104621.htm

Probing the Secrets of Sharp Memory in Old Age

March 24, 2010

Science Daily/American Chemical Society

A study of the brains of people who stayed mentally sharp into their 80s and beyond challenges the notion that brain changes linked to mental decline and Alzheimer's disease are a normal, inevitable part of aging.

In a presentation given at the 239th National Meeting of the American Chemical Society (ACS) in San Fransisco March 23, Changiz Geula, Ph.D. and colleagues described their discovery of elderly people with super-sharp memory -- so-called "super-aged" individuals -- who somehow escaped formation of brain "tangles."

The tangles consist of an abnormal form of a protein called "tau" that damages and eventually kills nerve cells. Named for their snarled, knotted appearance under a microscope, tangles increase with advancing age and peak in people with Alzheimer's disease.

"This discovery is very exciting," said Geula, principal investigator of the Northwestern University Super Aging Project and a professor of neuroscience at the Cognitive Neurology and Alzheimer's Disease Center. "It is the first study of its kind and its implications are vast.

We always assumed that the accumulation of tangles is a progressive phenomenon throughout the normal aging process. Healthy people develop moderate numbers of tangles, with the most severe cases linked to Alzheimer's disease. But now we have evidence that some individuals are immune to tangle formation.

The evidence also supports the notion that the presence of tangles may influence cognitive performance. Individuals with the fewest tangles perform at superior levels. Those with more appear to be normal for their age."’

The scientists found that super-aged people appear to fall into two subgroups: Those who are almost immune to tangle formation and those that have few tangles.

"One group of super-aged seems to dodge tangle formation," Geula explained. "Their brains are virtually clean, which doesn't happen in normal-aged individuals. The other group seems to get tangles but it's less than or equal to the amount in the normal elderly. But for some reason, they seem to be protected against its effects."

http://www.sciencedaily.com/releases/2010/03/100323212139.htm

Longevity hormone is lower in stressed, depressed women

June 16, 2015

Science Daily/University of California - San Francisco

Women under chronic stress have significantly lower levels of klotho, a hormone that regulates aging and enhances cognition, researchers have found in a study comparing mothers of children on the autism spectrum to low-stress controls.

The researchers found that the women in their study with clinically significant depressive symptoms had even lower levels of klotho in their blood than those who were under stress but not experiencing such symptoms.

The study, published June 16, in Translational Psychiatry, is the first to show a relationship between psychological influences and klotho, which performs a wide variety of functions in the body.

"Our findings suggest that klotho, which we now know is very important to health, could be a link between chronic stress and premature disease and death," said lead author, Aric Prather, PhD, an assistant professor of psychiatry at UCSF. "Since our study is observational, we cannot say that chronic stress directly caused lower klotho levels, but the new connection opens avenues of research that converge upon aging, mental health, and age-related diseases."

Scientists know from their work in mice and worms that, when klotho is disrupted, it promotes symptoms of aging, such as hardening of the arteries and the loss of muscle and bone, and when klotho is made more abundant, the animals live longer.

In previous work, senior author Dena Dubal, MD, PhD, showed that a genetic variant carried by one in five people is associated with having more klotho in the bloodstream, better cognitive function and a larger region of the prefrontal cortex. Carriers also tend to live longer and have lower rates of age-related disease. Dubal and colleagues found that increasing klotho in mice boosted their cognition and increased resilience to Alzheimer-related toxins, suggesting a therapeutic role for klotho in the brain.

The current study included 90 high-stress caregivers and 88 low-stress controls, most of whom were in their 30s and 40s and otherwise healthy. Klotho is known to decline with age, but in this cross-sectional study of relatively young women, this decline only happened among the high-stress women. The low-stress women did not show a significant reduction in klotho with aging.

"Chronic stress transmits risk for bad health outcomes in aging, including cardiovascular and Alzheimer's disease," said Dubal, an assistant professor in the UCSF Department of Neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease. "It will be important to figure out if higher levels of klotho can benefit mind and body health as we age. If so, therapeutics or lifestyle interventions that increase the longevity hormone could have a big impact on people's lives."

The researchers hypothesized that lower levels of klotho could contribute to stress and depression, since klotho acts on a variety of cellular, molecular and neural pathways that link to stress and depression.

http://www.sciencedaily.com/releases/2015/06/150616155903.htm

Brains evolved to need exercise

June 26, 2017

Science Daily/University of Arizona

Mounting scientific evidence shows that exercise is good not only for our bodies, but for our brains. Yet, exactly why physical activity benefits the brain is not well understood. Researchers suggest that the link between exercise and the brain is a product of our evolutionary history and our past as hunter-gatherers.

In a new article published in the journal Trends in Neurosciences, University of Arizona researchers suggest that the link between exercise and the brain is a product of our evolutionary history and our past as hunter-gatherers.

UA anthropologist David Raichlen and UA psychologist Gene Alexander, who together run a research program on exercise and the brain, propose an "adaptive capacity model" for understanding, from an evolutionary neuroscience perspective, how physical activity impacts brain structure and function.

Their argument: As humans transitioned from a relatively sedentary apelike existence to a more physically demanding hunter-gatherer lifestyle, starting around 2 million years ago, we began to engage in complex foraging tasks that were simultaneously physically and mentally demanding, and that may explain how physical activity and the brain came to be so connected.

"We think our physiology evolved to respond to those increases in physical activity levels, and those physiological adaptations go from your bones and your muscles, apparently all the way to your brain," said Raichlen, an associate professor in the UA School of Anthropology in the College of Social and Behavioral Sciences.

"It's very odd to think that moving your body should affect your brain in this way -- that exercise should have some beneficial impact on brain structure and function -- but if you start thinking about it from an evolutionary perspective, you can start to piece together why that system would adaptively respond to exercise challenges and stresses," he said.

Having this underlying understanding of the exercise-brain connection could help researchers come up with ways to enhance the benefits of exercise even further, and to develop effective interventions for age-related cognitive decline or even neurodegenerative diseases such as Alzheimer's.

Notably, the parts of the brain most taxed during a complex activity such as foraging -- areas that play a key role in memory and executive functions such as problem solving and planning -- are the same areas that seem to benefit from exercise in studies.

"Foraging is an incredibly complex cognitive behavior," Raichlen said. "You're moving on a landscape, you're using memory not only to know where to go but also to navigate your way back, you're paying attention to your surroundings. You're multitasking the entire time because you're making decisions while you're paying attention to the environment, while you are also monitoring your motor systems over complex terrain. Putting all that together creates a very complex multitasking effort."

The adaptive capacity model could help explain research findings such as those published by Raichlen and Alexander last year showing that runners' brains appear to be more connected than brains of non-runners.

The model also could help inform interventions for the cognitive decline that often accompanies aging -- in a period in life when physical activity levels tend to decline as well.

"What we're proposing is, if you're not sufficiently engaged in this kind of cognitively challenging aerobic activity, then this may be responsible for what we often see as healthy brain aging, where people start to show some diminished cognitive abilities," said Alexander, a UA professor of psychology, psychiatry, neuroscience and physiological sciences. "So the natural aging process might really be part of a reduced capacity in response to not being engaged enough."

Reduced capacity refers to what can happen in organ systems throughout the body when they are deprived of exercise.

"Our organ systems adapt to the stresses they undergo," said Raichlen, an avid runner and expert on running. "For example, if you engage in exercise, your cardiovascular system has to adapt to expand capacity, be it through enlarging your heart or increasing your vasculature, and that takes energy. So if you're not challenging it in that way -- if you're not engaging in aerobic exercise -- to save energy, your body simply reduces that capacity."

In the case of the brain, if it is not being stressed enough it may begin to atrophy. This may be especially concerning, considering how much more sedentary humans' lifestyles have become.

"Our evolutionary history suggests that we are, fundamentally, cognitively engaged endurance athletes, and that if we don't remain active we're going to have this loss of capacity in response to that," said Alexander, who studies brain aging and Alzheimer's disease as a member of the UA's Evelyn F. McKnight Brain Institute. "So there really may be a mismatch between our relatively sedentary lifestyles of today and how we evolved."

Alexander and Raichlen say future research should look at how different levels of exercise intensity, as well as different types of exercise, or exercise paired specifically with cognitive tasks, affect the brain.

For example, exercising in a novel environment that poses a new mental challenge, may prove to be especially beneficial, Raichlen said.

"Most of the research in this area puts people in a cognitively impoverished environment. They put people in a lab and have them run on a treadmill or exercise bike, and you don't really have to do as much, so it's possible that we're missing something by not increasing novelty," he said.

Alexander and Raichlen say they hope the adaptive capacity model will help advance research on exercise and the brain.

"This evolutionary neuroscience perspective is something that's been generally lacking in the field," Alexander said. "And we think this might be helpful to advance research and help develop some new specific hypotheses and ways to identify more universally effective interventions that could be helpful to everyone."

https://www.sciencedaily.com/releases/2017/06/170626155729.htm

Copper on the brain at rest

November 26, 2014

Science Daily/DOE/Lawrence Berkeley National Laboratory

Proper copper levels are essential to the health of the brain at rest, new research shows. The brain consumes 20-percent of the oxygen taken in through respiration. This high demand for oxygen and oxidative metabolism has resulted in the brain harboring the body's highest levels of copper, as well as iron and zinc. Over the past few years, researchers have developed a series of fluorescent probes for molecular imaging of copper in the brain.

In recent years it has been established that copper plays an essential role in the health of the human brain. Improper copper oxidation has been linked to several neurological disorders including Alzheimer's, Parkinson's, Menkes' and Wilson's. Copper has also been identified as a critical ingredient in the enzymes that activate the brain's neurotransmitters in response to stimuli. Now a new study by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) has shown that proper copper levels are also essential to the health of the brain at rest.

"The results of our study show that there are significant and similar preventive effects of PE and CT," the authors conclude. "Our finding suggests that delaying the intervention does not increase the risk of chronic PTSD…Thus, a delayed intervention is an acceptable option when early clinical interventions cannot be provided (e.g., during wars, disasters, or continuous hostilities)."

The results of this study suggest that the mismanagement of copper in the brain that has been linked to Wilson's, Alzheimer's and other neurological disorders can also contribute to misregulation of signaling in cell−to-cell communications.

"Our results hold therapeutic implications in that whether a patient needs copper supplements or copper chelators depends on how much copper is present and where in the brain it is located," Chang says. "These findings also highlight the continuing need to develop molecular imaging probes as pilot screening tools to help uncover unique and unexplored metal biology in living systems."

http://www.sciencedaily.com/releases/2014/11/141126124411.htm

A changing society: 100 is the new 80

Centenarians healthier than previously thought during last years of life

July 20, 2017

Science Daily/Charité - Universitätsmedizin Berlin

When it comes to aging successfully and remaining in good health, are centenarians the perfect role models? Researchers have been studying illness trajectories in centenarians during the final years of their lives. According to their findings, people who died aged 100 or older suffered fewer diseases than those who died aged 90 to 99, or 80 to 89.

Forty years ago, life expectancy was such that, in the industrialized world, only (approximately) one in 10,000 people were expected to reach the age of 100 or more. Today's estimates suggest that half of all children born in the developed world during this century will live to at least 100. Therefore, the question that poses itself is whether extreme old age is necessarily associated with increased morbidity. There is evidence to suggest that centenarians develop fewer diseases than younger cohorts of extreme old people. In discussions surrounding the issues associated with aging populations, this is referred to as the 'compression of morbidity' hypothesis -- a term which describes the phenomenon of the onset of disability and age-related diseases being increasingly being well into old age, resulting in a shortening (or compression) of this phase. "Our aim was to gain a better understanding of multimorbidity, i.e. the number and severity of chronic diseases affecting centenarians towards the end of their lives," explains Dr. Paul Gellert of Charité's Institute of Medical Sociology and Rehabilitation Science.

Using diagnoses and health care utilization data routinely collected by the German statutory health insurance company Knappschaft, the researchers studied relevant events during the final six years of life of approximately 1,400 of the oldest old. For the purposes of analysis, this cohort was then divided into three groups. Data on persons who had died aged 100 or older were compared with random samples of persons who had died in their eighties or nineties. The analysis, which included data on very old persons living in their own homes as well as data on those living in residential care, focused on comorbid conditions classified by the Elixhauser Comorbidity Index as being usually associated with in-hospital mortality. "According to the data, centenarians suffered from an average of 3.3 such conditions during the three months prior to their deaths, compared with an average of 4.6 conditions for those who had died in their eighties," says Dr. Gellert, summarizing the findings. "Our results also show that the increase in conditions seen during the last few years of life was lower in centenarians than in those who had died between the ages of 90 and 99, or 80 and 89."

If one includes disorders commonly associated with extreme old age, such as different types of dementia and musculoskeletal disorders, approximately half of all centenarians recorded a total of five or more comorbid conditions. The same number of comorbid conditions was found in 60 percent of persons who had died in their nineties and 66 percent of persons who had died in their eighties. While different types of dementia and heart failure were found to be more common among centenarians than among the younger cohorts, high blood pressure, cardiac arrhythmia, renal failure, and chronic diseases were less common in those who had died after reaching 100 years of age. The incidence of musculoskeletal disorders was found to be similar in all three age groups. While there appears to be a clear link between extreme old age and the number of diseases recorded, the extent to which this is the case requires careful analysis.

https://www.sciencedaily.com/releases/2017/07/170720103148.htm

Moderate drinking may protect against Alzheimer's and cognitive impairment

August 19, 2011

Science Daily/Loyola University Health System

Moderate social drinking may significantly reduce the risk of dementia and cognitive impairment, suggests a new analysis of 143 studies.

Wine was more beneficial than beer or spirits. But this finding was based on a relatively small number of studies, because most papers did not distinguish among different types of alcohol.

Heavy drinking (more than 3 to 5 drinks per day) was associated with a higher risk of cognitive impairment and dementia, but this finding was not statistically significant. "We don't recommend that nondrinkers start drinking," Neafsey said. "But moderate drinking -- if it is truly moderate -- can be beneficial." Moderate drinking is defined as a maximum of two drinks per day for men and 1 drink per day for women.

The researchers note that there are other things besides moderate drinking that can reduce the risk of dementia, including exercise, education and a Mediterranean diet high in fruits, vegetables, cereals, beans, nuts and seeds. Even gardening has been shown to reduce the risk of dementia.

http://www.sciencedaily.com/releases/2011/08/110816112134.htm

Exercise may help prevent brain damage caused by Alzheimer's disease

August 15, 2011

Science Daily/Elsevier

Regular exercise could help prevent brain damage associated with neurodegenerative diseases like Alzheimer's, according to new research.

"Exercise allows the brain to rapidly produce chemicals that prevent damaging inflammation," said Professor Jean Harry, who led the study at the National Institute of Environmental Health Sciences in the United States. "This could help us develop a therapeutic approach for early intervention in preventing damage to the brain."

Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults.

The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.

http://www.sciencedaily.com/releases/2011/08/110815095727.htm

Over half of Alzheimer's cases may be preventable

July 19, 2011

Science Daily/University of California - San Francisco

Over half of all Alzheimer's disease cases could potentially be prevented through lifestyle changes and treatment or prevention of chronic medical conditions, according to a new study.

Analyzing data from studies around the world involving hundreds of thousands of participants, Barnes concluded that worldwide, the biggest modifiable risk factors for Alzheimer's disease are, in descending order of magnitude, low education, smoking, physical inactivity, depression, mid-life hypertension, diabetes and mid-life obesity.

In the United States, Barnes found that the biggest modifiable risk factors are physical inactivity, depression, smoking, mid-life hypertension, mid-life obesity, low education and diabetes.

Together, these risk factors are associated with up to 51 percent of Alzheimer's cases worldwide (17.2 million cases) and up to 54 percent of Alzheimer's cases in the United States (2.9 million cases), according to Barnes.

"What's exciting is that this suggests that some very simple lifestyle changes, such as increasing physical activity and quitting smoking, could have a tremendous impact on preventing Alzheimer's and other dementias in the United States and worldwide," said Barnes, who is also an associate professor of psychiatry at the University of California, San Francisco.

http://www.sciencedaily.com/releases/2011/07/110719072809.htm