Bacterial metabolism of dietary soy may lower risk factor for dementia

October 22, 2020

Science Daily/University of Pittsburgh

A metabolite produced following consumption of dietary soy may decrease a key risk factor for dementia -- with the help of the right bacteria, according to a new discovery led by researchers at the University of Pittsburgh Graduate School of Public Health.

Their study, published today in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions, reports that elderly Japanese men and women who produce equol -- a metabolite of dietary soy created by certain types of gut bacteria -- display lower levels of white matter lesions within the brain.

"White matter lesions are significant risk factors for cognitive decline, dementia and all-cause mortality," said lead author Akira Sekikawa, M.D., Ph.D., associate professor of epidemiology at Pitt Public Health. "We found 50% more white matter lesions in people who cannot produce equol compared to people who can produce it, which is a surprisingly huge effect."

To obtain this result, Sekikawa's research team measured equol levels within the blood of 91 elderly Japanese participants with normal cognition. Participants were sorted by their equol production status, and then six to nine years later underwent brain imaging to detect levels of white matter lesions and deposits of amyloid-beta, which is the suspected molecular cause of Alzheimer's disease.

The researchers found that while equol production did not appear to impact levels of amyloid-beta deposited within the brain, it was associated with reduced white matter lesion volumes. Sekikawa's team also discovered that high levels of isoflavones -- soy nutrients that are metabolized into equol -- had no effect on levels of white matter lesions or amyloid-beta when equol wasn't produced.

According to Sekikawa, the ability to produce equol from soy isoflavones may be the key to unlocking protective health benefits from a soy-rich diet, and his team has previously shown that equol production is associated with a lower risk of heart disease. As heart disease is strongly associated with cognitive decline and dementia, equol production could help protect the aging brain as well as the heart.

Epidemiological studies in Japan, where soy is regularly consumed, have shown that dietary intake of soy isoflavones has been linked to a lower risk for heart disease and dementia. However, most clinical trials in America have failed to show this.

Sekikawa believes that this discrepancy may be due to the microbiome -- 40-70% of Japanese harbor gut bacteria that can convert dietary isoflavones into equol compared to only 20-30% of Americans.

Sekikawa said that equol supplements could one day be combined with existing diet-based prevention strategies that appear to lower the risk of dementia, particularly the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets.

Though Sekikawa hopes to evaluate the neuroprotective effects of equol supplements in a future randomized clinical trial, in the meantime, he urges caution to anyone who might be tempted to purchase equol supplements to stave off dementia.

"This type of study always catches people's attention, but we cannot prove that equol protects against dementia until we get a randomized clinical trial with sufficient evidence," he said.

https://www.sciencedaily.com/releases/2020/10/201022083311.htm

Gut hormone blocks brain cell formation and is linked to Parkinson's dementia

October 22, 2020

Science Daily/Swansea University

A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson's Disease.

Blood-borne factors such as hormones regulate the process of brain cell formation -- known as neurogenesis -- and cognition in adult mammals.

The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).

The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.

This research is relevant to Parkinson's as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.

The team's key overall findings were:

• the UAG form of ghrelin reduces nerve cell formation and impairs memory

• Individuals diagnosed with Parkinson's disease dementia have a reduced AG:UAG ratio in their blood

Dr Jeff Davies of Swansea University Medical School, lead researcher, said:

"Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically.

This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson's.

Our findings show that the AG:UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson's disease."

The team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson's disease patients diagnosed with dementia with cognitively intact PD patients and a control group.

They found:

• Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.

• AG helped reverse spatial memory impairments

• UAG blocks the process of brain cell formation prompted by AG

• The Parkinson's patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.

https://www.sciencedaily.com/releases/2020/10/201022183809.htm

Exercise and nutrition regimen benefit physical, cognitive health

12-week double-blind control trial in 148 Air Force airmen

October 19, 2020

Science Daily/University of Illinois at Urbana-Champaign, News Bureau

Researchers studied the effects of a 12-week exercise regimen on 148 active-duty Air Force airmen, half of whom also received a twice-daily nutrient beverage that included protein; the omega-3 fatty acid, DHA; lutein; phospholipids; vitamin D; B vitamins and other micronutrients; along with a muscle-promoting compound known as HMB. Both groups improved in physical and cognitive function, with added gains among those who regularly consumed the nutritional beverage, the team reports.

The findings appear in the journal Scientific Reports.

Participants were randomly assigned to the two groups. The exercise regimen combined strength training and high-intensity interval aerobic fitness challenges. One group received the nutritional beverage and the other consumed a placebo beverage that lacked the added nutrients. Neither the researchers nor the participants knew who received the nutrient-enriched beverage or placebo.

"The exercise intervention alone improved strength and endurance, mobility and stability, and participants also saw increases in several measures of cognitive function. They had better episodic memory and processed information more efficiently at the end of the 12 weeks. And they did better on tests that required them to solve problems they had never encountered before, an aptitude called fluid intelligence," said Aron Barbey, a professor of psychology at the University of Illinois at Urbana-Champaign who led the study with postdoctoral researcher Christopher Zwilling.

"Those who also consumed the nutritional supplement saw all of these improvements and more. For example, they were better able to retain new information in their working memory and had quicker responses on tests of fluid intelligence than those taking the placebo," Barbey said.

Physical power increased in both groups as a result of the physical training, Zwilling said.

"Power is a measure of physical fitness that is based on several factors, such as how fast a participant can pull a heavy sled over a set distance, how far they can toss a weighted ball, and how many pushups, pullups or situps they can perform in a set time period," he said.

The physical training reduced participants' body fat percentage and increased their oxygen-uptake efficiency, or VO2 max. The airmen also performed better than they had initially on several measures of cognitive function. The most notable of these was an increase in the accuracy of their responses to problems designed to measure fluid intelligence.

"But we also wanted to know whether taking the supplement conferred an advantage above and beyond the effect of exercise," Zwilling said. "We saw that it did, for example in relationship to resting heart rate, which went down more in those who took the supplement than in those who didn't."

Participants who consumed the nutritional beverage also saw greater improvements in their ability to retain and process information. And their reaction time on tests of fluid intelligence improved more than their peers who took the placebo, the researchers found.

"Our work motivates the design of novel multimodal interventions that incorporate both aerobic fitness training and nutritional supplementation, and illustrates that their benefits extend beyond improvements in physical fitness to enhance multiple measures of cognitive function," Barbey said.

The U. of I. team conducted the intervention with study co-author Adam Strang, a scientist in the Applied Neuroscience Branch of Wright-Patterson Air Force Base near Dayton, Ohio, along with his colleagues in the Air Force Research Laboratory. The U. of I. team also worked with research fellow and study co-author Tapas Das and his colleagues at Abbott Nutrition, who led the design of the nutritional beverage, which is a mixture of nutrients targeting both muscle and brain. The specially designed beverage provided ingredients that previous studies have shown are associated with improved physical cognitive function.

https://www.sciencedaily.com/releases/2020/10/201019103508.htm

Could loss of interest be sign of dementia risk?

October 14, 2020

Science Daily/American Academy of Neurology

Older adults with severe apathy, or lack of interest in usual activities, may have a greater chance of developing dementia than people with few symptoms of apathy, according to a study published in the October 14, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Apathy can be very distressing for family members, when people no longer want to get together with family or friends or don't seem interested in what they used to enjoy," said study author Meredith Bock, M.D., of the University of California, San Francisco. "More research is needed, but it's possible that these are signs that people may be at risk for Alzheimer's disease and could benefit from early interventions and efforts to reduce other risk factors."

The study involved 2,018 adults with an average age of 74. None had dementia. At the start of the study, researchers measured apathy using a survey with questions such as "In the past four weeks, how often have you been interested in leaving your home and going out?" and "In the past 4 weeks, how often have you been interested in doing your usual activities?" Participants were then divided into three groups: those with low, moderate and severe apathy. After nine years, researchers determined who had dementia by looking at medication use, hospital records and results on cognitive tests.

By the end of the study, 381 participants, or almost 19%, developed dementia. In the low apathy group, 111 out of 768 people, or 14%, developed dementia, compared to 143 out of 742 people, or 19%, in the moderate apathy group. In the severe apathy group, 127 out of 508 people, or 25%, developed dementia. After adjusting for age, education, cardiovascular risk factors and other factors that could affect dementia risk, they found that people with severe apathy were 80% more likely to develop dementia than people with low apathy.

Greater apathy was also associated with worse cognitive score at the beginning of the study.

"While depression has been studied more extensively as a predictor of dementia, our study adds to the research showing that apathy also deserves attention as an independent predictor of the disease," Bock said. "In fact, we believe that apathy may be a very early sign of dementia and it can be evaluated with a brief questionnaire."

A limitation of the study is that an algorithm was used to diagnose dementia, which may not be as sensitive as an in-depth evaluation by a doctor.

https://www.sciencedaily.com/releases/2020/10/201014160514.htm

One-two punch of symptoms that exacerbate Alzheimer's

Research finds that impaired blood flow in the brain is correlated with the buildup of tau tangles, a hallmark indicator of cognitive decline

October 16, 2020

Science Daily/University of Southern California

A new Alzheimer's study found that impaired blood flow in the brain is correlated with the buildup of tau tangles, a hallmark indicator of cognitive decline.

The work, published this week in the Journal of Neuroscience, suggests that treatments targeting vascular health in the brain -- as well as amyloid plaques and tau tangles -- may be more effective in preserving memory and cognitive function than single-target therapies.

"This study confirms that we should carefully consider vascular health and associated risk factors -- like high blood pressure, smoking and physical inactivity -- in the course of Alzheimer's prevention," said Judy Pa, an associate professor of neurology at the Keck School of Medicine of USC's Mark and Mary Stevens Neuroimaging and Informatics Institute (INI) and the study's senior author.

Researchers wanted to understand how restricted blood flow in the brain relates to the buildup of tau proteins characteristic of Alzheimer's disease. To do so, the team examined MRI and PET images, as well as cerebrospinal fluid, among two groups: cognitively normal individuals and those at various stages of dementia, including mild cognitive impairment and Alzheimer's disease.

Pa and her colleagues found that those with a strong overlap between vascular dysfunction and tau pathology in key Alzheimer's brain regions had the worst cognitive symptoms.

"This connection was most pronounced among those in more advanced stages of the disease, suggesting that the pathway corresponds to cognitive decline over time," Pa said.

That finding is particularly important because it suggests the pathway could be a useful biological marker for measuring Alzheimer's progression in patients. The effect was also most pronounced in amyloid-positive individuals, pointing to a relationship between cerebrovascular, tau and amyloid pathologies.

The research team included a group of experts from the INI and across the Keck School of Medicine's departments of neurology, radiology and physiology and neuroscience. Future steps include evaluating how the synergy between these pathologies relates to cognitive decline over time.

"We're now starting to fully appreciate the role of vascular dysfunction in Alzheimer's disease," said Arthur W. Toga, a coauthor of the study and director of the INI. "Controlling risk factors like smoking and high blood pressure are accessible lifestyle modifications that offer hope for those at risk."

https://www.sciencedaily.com/releases/2020/10/201016090155.htm

Evidence of Alzheimer's, Parkinson's and MND in brains of young people exposed to dirty air

October 6, 2020

Science Daily/Lancaster University

After examining the brainstems of 186 young Mexico City residents aged between 11 months and 27 years of age, researchers, found markers not only of Alzheimer's disease, but also of Parkinson's and of motor neuron disease (MND) too. These markers of disease were coupled with the presence of tiny, distinctive nanoparticles within the brainstem - their appearance and composition indicating they were likely to come from vehicle pollution.

Researchers looking at the brainstems of children and young adults exposed lifelong to air pollution in Mexico City have discovered disturbing evidence of harm.

Previous studies have linked fine particulate air pollution exposure with Alzheimer's disease, and researchers have also reported evidence of air pollution-derived nanoparticles in the frontal cortex of the brain.

But after examining the brainstems of 186 young Mexico City residents aged between 11 months and 27 years of age, researchers, including Professor Barbara Maher from Lancaster University, found markers not only of Alzheimer's disease, but also of Parkinson's and of motor neurone disease (MND) too. These markers of disease were coupled with the presence of tiny, distinctive nanoparticles within the brainstem -- their appearance and composition indicating they were likely to come from vehicle pollution.

This has led researchers to conclude that air pollution of this nature -- whether inhaled or swallowed -- puts people at risk of potential neurological harm. The brainstem is the posterior part of the brain which regulates the central nervous system, controls heart and breathing rates, and how we perceive the position and movement of our body, including, for example, our sense of balance.

Professor Maher said: "Not only did the brainstems of the young people in the study show the 'neuropathological hallmarks' of Alzheimer's, Parkinson's and MND, they also had high concentrations of iron-, aluminium- and titanium-rich nanoparticles in the brainstem -- specifically in the substantia nigra, and cerebellum.

"The iron-and aluminium-rich nanoparticles found in the brainstem are strikingly similar to those which occur as combustion- and friction-derived particles in air pollution (from engines and braking systems).

"The titanium-rich particles in the brain were different -- distinctively needle-like in shape; similar particles were observed in the nerve cells of the gut wall, suggesting these particles reach the brain after being swallowed and moving from the gut into the nerve cells which connect the brainstem with the digestive system."

The 'neuropathological hallmarks' found even in the youngest infant (11 months old) included nerve cell growths, and plaques and tangles formed by misfolded proteins in the brain. Damage to the substantia nigra is directly linked with the development of Parkinson's disease in later life. Protein misfolding linked previously with MND was also evident, suggesting common causal mechanisms and pathways of formation, aggregation and propagation of these abnormal proteins.

The one thing common to all of the young people examined in the study was their exposure to high levels of particulate air pollution. Professor Maher says that the associations between the presence of damage to cells and their individual components -- especially the mitochondria (key for generation of energy, and signalling between cells) -- and these metal-rich nanoparticles are a 'smoking gun'.

Such metal-rich particles can cause inflammation and also act as catalysts for excess formation of reactive oxygen species, which are known to cause oxidative stress and eventual death of neurons. Critically, the brainstems of age- and gender- matched controls who lived in lower-pollution areas have not shown the neurodegenerative pathology seen in the young Mexico City residents.

These new findings show that pollution-derived, metal-rich nanoparticles can reach the brainstem whether by inhalation or swallowing, and that they are associated with damage to key components of nerve cells in the brainstem, including the substantia nigra.

Even in these young Mexico City residents, the type of neurological damage associated with Alzheimer's, Parkinson's and motor neurone diseases is already evident. These data indicate the potential for a pandemic of neurological disease in high-pollution cities around the world as people experience longer lifespans, and full symptoms of earlier, chronic neurological damage develop.

Professor Barbara Maher said: "It's critical to understand the links between the nanoparticles you're breathing in or swallowing and the impacts those metal-rich particles are then having on the different areas of your brain.

"Different people will have different levels of vulnerability to such particulate exposure but our new findings indicate that what air pollutants you are exposed to, what you are inhaling and swallowing, are really significant in development of neurological damage.

"With this in mind, control of nanoparticulate sources of air pollution becomes critical and urgent."

https://www.sciencedaily.com/releases/2020/10/201006153526.htm

Older people with early, asymptomatic Alzheimer's at risk of falls

Even without cognitive problems, those with Alzheimer's-related brain damage at increased risk of falls

September 15, 2020

Science Daily/Washington University School of Medicine

Falls are the leading cause of fatal injuries in older adults, causing more than 800,000 hospitalizations and about 30,000 deaths in the U.S. every year. Some risk factors are well-known -- advanced age, problems with vision or balance, muscle weakness -- but an under-recognized factor is early Alzheimer's disease. Older people in the earliest stages of Alzheimer's, before cognitive problems arise, are more likely to suffer a fall than people who are not on track to develop dementia.

Researchers at Washington University School of Medicine in St. Louis have found that, in older people without cognitive problems who experience a fall, the process of neurodegeneration that leads to Alzheimer's dementia already may have begun. The findings, available online in the Journal of Alzheimer's Disease, suggest that older people who have experienced falls should be screened for Alzheimer's and that new strategies may be needed to reduce the risk of falling for people in the disease's early stages.

"In the world of fall research, we generally say that you're at risk of falling if you lose strength and balance," said co-senior author Susan Stark, PhD, an associate professor of occupational therapy, of neurology and of social work. "If you lose strength and balance, the recommended treatment is to work on strength and balance. But if someone is falling for another reason, maybe because his or her brain has begun accumulating Alzheimer's-related damage, that person might need a different treatment entirely. We don't yet know what that treatment might be, but we hope we can use this information to come up with new treatment recommendations that will reduce the risk of falls in this population."

In 1987, John C. Morris, MD, then a trainee at Washington University, discovered that older people with Alzheimer's dementia are more than twice as likely to suffer a traumatic fall than people of the same age without dementia. Morris is now the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology and head of the university's Charles F. and Joanne Knight Alzheimer's Disease Research Center.

Since Morris' discovery more than three decades ago, scientists have learned that the brains of Alzheimer's patients start undergoing changes decades before memory loss and confusion become apparent. First, plaques of amyloid proteins form, then tangles of tau protein. Some brain areas begin to shrink, and communication networks between distant parts of the brain start to decay. Stark and colleagues have shown that the link between Alzheimer's and falling holds true even during the silent phase of the disease: People with so-called preclinical Alzheimer's are at increased risk of falling despite having no apparent cognitive problems.

To better understand why people without cognitive symptoms are at risk of falling, first author Audrey Kelemen, a graduate student in Stark's lab, and colleagues followed 83 people over age 65 for a year. All participants were assessed as cognitively normal by a qualified neurologist at the beginning of the study. Each participant filled out monthly calendars recording any falls and underwent brain scans for amyloid and for signs of atrophy and impaired connectivity.

The researchers discovered that the presence of amyloid in the brain alone did not put people at increased risk of falling but that neurodegeneration did. Participants who fell had smaller hippocampi -- brain regions that are devoted to memory and that shrink in Alzheimer's disease. Their somatomotor networks -- webs of connections that are involved in receiving sensory inputs and controlling movement -- also showed signs of decay. The researchers concluded that falling is most likely to occur in the neurodegeneration phase of preclinical Alzheimer's -- the last five years or so before memory loss and confusion arise.

"Since I started working on this project, I've started asking my patients about falls, and I can't tell you how often that has helped me start understanding what is going on with the individual," said co-senior author Beau M. Ances, MD, PhD, the Daniel J. Brennan, MD, Professor of Neurology and a professor of radiology and of biomedical engineering. Ances treats patients who have dementia and other neurological conditions on the Washington University Medical Campus.

"When a person's mobility is being diminished, even though the person looks very normal, that could be a sign that something needs further evaluation," Ances said. "It's actually a really important potential marker that should make us say, 'Wait a minute. Let's dive into this more. Are there other things that go along with it?'"

The researchers have begun further experiments to better understand why brain changes in Alzheimer's put people at risk of falling, so they can develop fall-prevention recommendations. In the meantime, simple changes could go a long way toward protecting older people from devastating falls, Stark said.

"You can prevent a lot of falls just by making the environment safer," Stark said. "Simple changes could help and can't hurt: making sure the tub isn't slippery; making sure you can get up easily off the toilet; balance and strength training; reviewing your prescriptions to see if certain medications or combinations of medications are increasing the risk of falling. Until we have specific fall-prevention treatments for people with preclinical Alzheimer's, there are still plenty of things we can do to make people safer."

https://www.sciencedaily.com/releases/2020/09/200915140133.htm

Vitamin B1 deficiency a key factor in the development of alcohol-related dementia

Hypothesis describes the role of iron deposits in the brain as the cause of dementia in alcoholics

September 9, 2020

Science Daily/Medical University of Vienna

A common consequence of chronically high alcohol consumption is a decline in cognitive function, which can even progress to full-blown dementia. However, we do not yet fully understand how alcohol damages the brain. A research group led by Stephan Listabarth from MedUni Vienna's Department of Psychiatry and Psychotherapy, Division of Social Psychiatry, has now developed a hypothesis whereby iron deposits in the brain -- resulting from alcohol-induced vitamin B1 deficiency -- can be regarded as key factors in cognitive decline. The work has now been published in the leading journal Alzheimer's and Dementia. 

In Austria, around 5% of the population are alcohol dependent from the age of 15 onwards. This means that approximately 365,000 people are affected by the dangerous health consequences associated with high alcohol consumption. One of these consequences is a decline in cognitive function, especially memory and abstraction. This is then referred to as alcohol-related dementia. However, we do not yet fully understand the exact pathomechanism, that is to say the way in which the brain is damaged by alcohol.

Researchers Stephan Listabarth, Daniel König and Benjamin Vyssoki from the Department of Psychiatry and Psychotherapy, Division of Social Psychiatry at MedUni Vienna and Simon Hametner from MedUni Vienna's Department of Neurology, Division of Neuropathology and Neurochemistry, have now advanced a plausible hypothesis to explain alcohol-induced brain damage: the cognitive deterioration is caused by iron deposits in the brain but the administration of vitamin B1 could protect the brain from these deposits.

We know from various neurodegenerative diseases that iron deposits in the brain are responsible for nerve tissue damage. These deposits can also be detected in specific regions of the brain (including the basal ganglia) in people who drink a lot of alcohol. The hypothesis advanced by the study authors now also offers an explanation as to why iron deposits are so prevalent in this patient group: high alcohol consumption results in elevated iron levels in the blood and also to vitamin B1 (thiamine) deficiency, which, among other things, is important for maintaining the blood-brain barrier. If these two situations coincide, more iron will be deposited inside the brain, ultimately leading to oxidative tissue damage.

This newly described role of vitamin B1 in this process could represent a huge step forward in our understanding of the development of alcohol-related neurological damage and, in particular, could offer a new point of attack for preventive and therapeutic approaches. It would then be conceivable to give continuous vitamin B1 substitutionin future, as a preventive measure.

The researchers believe it would also be useful to evaluate the use of drugs to reduce iron levels (e.g. chelators), as is already done in other neurodegenerative diseases. The authors of the current work have already started planning a prospective clinical study to validate the above-mentioned relationship between alcohol dependency, vitamin B1 deficiency and cerebral iron deposits and to provide a basis for further research in the field of alcohol-related dementia in the future.

https://www.sciencedaily.com/releases/2020/09/200909100248.htm

Understanding the link between hearing loss and dementia

September 1, 2020

Science Daily/Newcastle University

Scientists have developed a new theory as to how hearing loss may cause dementia and believe that tackling this sensory impairment early may help to prevent the disease.

Hearing loss has been shown to be linked to dementia in epidemiological studies and may be responsible for a tenth of the 47 million cases worldwide.

Now, published in the journal Neuron, a team at Newcastle University, UK, provide a new theory to explain how a disorder of the ear can lead to Alzheimer's disease -- a concept never looked at before.

It is hoped that this new understanding may be a significant step towards advancing research into Alzheimer's disease and how to prevent the illness for future generations.

Newcastle experts considered three key aspects; a common underlying cause for hearing loss and dementia; lack of sound-related input leading to brain shrinking; and cognitive impairment resulting in people having to engage more brain resources to compensate for hearing loss, which then become unavailable for other tasks.

The team propose a new angle which focuses on the memory centres deep in the temporal lobe. Their recent work indicates that this part of the brain, typically associated with long-term memory for places and events, is also involved in short-term storage and manipulation of auditory information.

They consider explanations for how changes in brain activity due to hearing loss might directly promote the presence of abnormal proteins that cause Alzheimer's disease, therefore triggering the disease.

Professor Tim Griffiths, from Newcastle University's Faculty of Medical Sciences, said: "The challenge has been to explain how a disorder of the ear can lead to a degenerative problem in the brain.

"We suggest a new theory based on how we use what is generally considered to be the memory system in the brain when we have difficulty listening in real-world environments."

Work on mechanisms for difficult listening is a central theme for the research group, including members in Newcastle, UCL and Iowa University, that has been supported by a Medical Research Council programme grant.

Dr Will Sedley, from Newcastle University's Faculty of Medical Sciences, said: "This memory system engaged in difficult listening is the most common site for the onset of Alzheimer's disease.

"We propose that altered activity in the memory system caused by hearing loss and the Alzheimer's disease process trigger each other.

"Researchers now need to examine this mechanism in models of the pathological process to test if this new theory is right."

The experts developed the theory of this important link with hearing loss by bringing together findings from a variety of human studies and animal models. Future work will continue to look at this area.

https://www.sciencedaily.com/releases/2020/09/200901112218.htm

Higher dementia risk in women with prolonged fertility

September 17, 2020

Science Daily/University of Gothenburg

Women with a longer reproductive period had an elevated risk for dementia in old age, compared with those who were fertile for a shorter period, a population-based study from the University of Gothenburg shows.

"Our results may explain why women have a higher risk of developing dementia and Alzheimer's disease than men after age 85, and provide further support for the hypothesis that estrogen affect the risk of dementia among women," says Jenna Najar, a medical doctor and doctoral student at Sahlgrenska Academy who also works at AgeCap, the Centre for Ageing and Health at the University of Gothenburg.

The study, now published in the journal Alzheimer's & Dementia, covers 1,364 women who were followed between 1968 and 2012 in the population studies collectively known as the "Prospective Population-based Study of Women in Gothenburg" (PPSW) and the "Gothenburg H70 Birth Cohort Studies in Sweden" (the H70 studies). The "reproduction period" spans the years between menarche (onset of menstruation) and menopause, when menstruation ceases.

Of the women studied with a shorter reproductive period (32.6 years or less), 16 percent (53 of 333 individuals) developed dementia. In the group of women who were fertile a longer period (38 years or more), 24 percent (88 of 364) developed dementia. The difference was thus 8 percentage points.

The study shows that risk for dementia and Alzheimer's disease increases successively for every additional year that the woman remains fertile. The association was strongest for those with dementia onset after age 85, and the effect was most strongly associated with age at menopause.

These results persisted after adjustment for other factors with an influence, such as educational attainment, physical activity, BMI, smoking, and cardiovascular disease. On the other hand, no association was found between dementia risk and age at menarche, number of pregnancies, duration of breastfeeding, or exogenous estrogen taken in the form of hormonal replacement therapy (HRT) or oral contraceptives.

Several studies have investigated how estrogen in the form of HRT affects dementia risk. Some studies show that dementia risk falls and others that it rises, especially in women who take estrogen late in life.

In the current study Jenna Najar has, instead, investigated the long-term association between factors related to endogenous estrogen and dementia.

"What's novel about this study, too, is that we've had access to information about several events in a woman's life that can affect her estrogen levels. Examples are pregnancies, births, and breastfeeding. Being pregnant boosts estrogen levels tremendously; then they decline once the baby is born, and if women breastfeed the levels fall to extremely low levels. The more indicators we capture, the more reliable our results are," Najar says.

Ingmar Skoog, professor of psychiatry at Sahlgrenska Academy, University of Gothenburg and head of AgeCap, led the study.

"The varying results for estrogen may be due to it having a protective effect early in life but being potentially harmful once the disease has begun."

At the same time, Skoog points out that the duration of women's fertile periods is one risk factor for dementia among many.

Most women whose menopause is delayed do not develop dementia because of this factor alone. However, the study may provide a clue as to why women are at higher risk than men for dementia after age 85, the most common age of onset. Alzheimer's disease, on the other hand, starts developing some 20 years before symptoms of the disorder become apparent.

"Most people affected are over 80 and female," Najar says.

"As a result of global ageing, the number of people affected by dementia will increase. To be able to implement preventive strategies, we need to identify people with an elevated risk of dementia."

https://www.sciencedaily.com/releases/2020/09/200917105419.htm

Education may be protective for people with gene for familial early onset Alzheimer's

August 5, 2020

Science Daily/American Academy of Neurology

Even for people who carry the gene for early onset Alzheimer's disease, more years of education may slow the development of beta-amyloid plaques in the brain that are associated with the disease, according to a new study published in the August 5, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

About 1-6% of people with Alzheimer's disease have rare genes that cause the disease in everyone who has them. This is called familial Alzheimer's disease. It leads to an early onset of the disease, when people are in their 30s to 50s.

"Because we've assumed that the effects of these genes can't be changed, very little research has been done on whether we can modify the trajectory of the disease," said study author Sylvia Villeneuve, PhD, of the McGill University in Montreal, Canada. "It's exciting to see that education may play a role in delaying the start of this devastating disease, which affects people during the prime of life."

Most people diagnosed with Alzheimer's have the sporadic form of the disease, which is thought to be caused by a combination of both environmental and genetic factors, including a gene variant called APOE ?4, or apolipoprotein E ?4. Having this gene variant is known to increase the development of amyloid plaques in the brain, even though it does not guarantee that the person will develop symptoms of Alzheimer's disease.

The study involved two groups: one group of 106 people with an average age of 67 who had a parent diagnosed with the sporadic form of Alzheimer's disease, of whom 39% had the APOE ?4 gene variant; and another group of 117 people with an average age of 35 who had the gene mutations linked to familial early onset Alzheimer's disease, of whom 31% also had the APOE ?4 gene variant. Each group had an average 15 years of education. None of the participants showed symptoms of the disease at the start of the study.

Participants had brain scans to determine levels of amyloid plaques.

Researchers found that in the people with familial early onset Alzheimer's, increasing levels of education were associated with lower levels of amyloid plaques in the brain. The strength of the association between education and plaque levels was similar to the strength of this same association in people at risk of sporadic Alzheimer's disease.

In both groups, people with less than 10 years of education had about twice the amount of amyloid plaques when compared to people with more than 16 years of education.

"While it has been believed that people with familial Alzheimer's disease, with its strong genetic causes, may have few ways to slow development of the disease, our study shows that education may be somewhat protective, perhaps promoting brain resistance against these plaques, just as it has been shown to be in people with unknown causes of the disease," said Villeneuve.

A limitation of the study was that most participants were white, so results may not be the same for all people. Also, the quality of education may be affected by other factors like socioeconomic status, so future studies should look more closely at other factors in addition to years of education to determine whether other environmental factors may be at play to explain these study results.

https://www.sciencedaily.com/releases/2020/08/200805160829.htm

Can sleep protect us from forgetting old memories?

Computational models examine how sleep encodes new memories while preventing damage to old ones

August 4, 2020

Science Daily/University of California - San Diego

From lowering your risk of obesity and cardiovascular disease to improving your concentration and overall daily performance, sleep has been proven to play a critical role in our health. In a new study, researchers at University of California San Diego School of Medicine report that sleep may also help people to learn continuously through their lifetime.

Writing in the August 4, 2020 online issue of eLife, researchers used computational models capable of simulating different brain states, such as sleep and awake, to examine how sleep consolidates newly encoded memories and prevents damage to old memories.

"The brain is very busy when we sleep, repeating what we have learned during the day. Sleep helps reorganize memories and presents them in the most efficient way. Our findings suggest that memories are dynamic, not static. In other words, memories, even old memories, are not final. Sleep constantly updates them," said Maksim Bazhenov, PhD, lead author of the study and professor of medicine at UC San Diego. "We predict that during the sleep cycle, both old and new memories are spontaneously replayed, which prevents forgetting and increases recall performance."

Bazhenov said that memory replay during sleep plays a protective role against forgetting by allowing the same populations of neurons to store multiple interfering memories. "We learn many new things on a daily basis and those memories compete with old memories. To accommodate all memories, we need sleep."

For example, imagine learning how to navigate to a parking lot by going left at one stop sign and right at one traffic light. The next day, you have to learn how to get to a different parking lot using different directions. Bazhenov said sleep consolidates those memories to allow recollection of both.

"When you play tennis, you have a certain muscle memory. If you then learn how to play golf, you have to learn how to move the same muscles in a different way. Sleep makes sure that learning golf does not erase how to play tennis and makes it possible for different memories to coexist in the brain," said Bazhenov.

The authors suggest that the restorative value of sleep may be what is lacking in current state-of-the-art computer systems that power self-driving cars and recognize images with performances that far exceed humans. However, these artificial intelligence systems lack the ability to learn continuously and will forget old knowledge when new information is learned. "We may need to add a sleep-like state to computer and robotic systems to prevent forgetting after new learning and to make them able to learn continuously," said Bazhenov.

Bazhenov said the study results could lead to developing new stimulation techniques during sleep to improve memory and learning. This may be particularly important in older adults or persons suffering from learning disabilities.

"While sleep is certainly involved in many important brain and body functions, it may be critical for making possible what we call human intelligence -- the ability to learn continuously from experience, to create new knowledge and to adapt as the world changes around us," said Bazhenov.

https://www.sciencedaily.com/releases/2020/08/200804122233.htm

New study shows how infrared lasers destroy harmful protein aggregates in Alzheimer's

August 4, 2020

Science Daily/Tokyo University of Science

The agglomeration of proteins into structures called amyloid plaques is a common feature of many neurodegenerative diseases, including Alzheimer's. Now, scientists reveal, through experiments and simulations, how resonance with an infrared laser, when it is tuned to a specific frequency, causes amyloid fibrils to disintegrate from the inside out. Their findings open doors to novel therapeutic possibilities for amyloid plaque-related neurodegenerative diseases that have thus far been incurable.

A notable characteristic of several neurodegenerative diseases, such as Alzheimer's and Parkinson's, is the formation of harmful plaques that contain aggregates -- also known as fibrils -- of amyloid proteins. Unfortunately, even after decades of research, getting rid of these plaques has remained a herculean challenge. Thus, the treatment options available to patients with these disorders are limited and not very effective.

In recent years, instead of going down the chemical route using drugs, some scientists have turned to alternative approaches, such as ultrasound, to destroy amyloid fibrils and halt the progression of Alzheimer's disease. Now, a research team led by Dr Takayasu Kawasaki (IR-FEL Research Center, Tokyo University of Science, Japan) and Dr Phuong H. Nguyen (Centre National de la Recherche Scientifique, France), including other researchers from the Aichi Synchrotron Radiation Center and the Synchrotron Radiation Research Center, Nagoya University, Japan, has used novel methods to show how infrared-laser irradiation can destroy amyloid fibrils.

In their study, published in Journal of Physical Chemistry B, the scientists present the results of laser experiments and molecular dynamics simulations. This two-pronged attack on the problem was necessary because of the inherent limitations of each approach, as Dr Kawasaki explains, "While laser experiments coupled with various microscopy methods can provide information about the morphology and structural evolution of amyloid fibrils after laser irradiation, these experiments have limited spatial and temporal resolutions, thus preventing a full understanding of the underlying molecular mechanisms. On the other hand, though this information can be obtained from molecular simulations, the laser intensity and irradiation time used in simulations are very different from those used in actual experiments. It is therefore important to determine whether the process of laser-induced fibril dissociation obtained through experiments and simulations is similar."

The scientists used a portion of a yeast protein that is known to form amyloid fibrils on its own. In their laser experiments, they tuned the frequency of an infrared laser beam to that of the "amide I band" of the fibril, creating resonance. Scanning electron microscopy images confirmed that the amyloid fibrils disassembled upon laser irradiation at the resonance frequency, and a combination of spectroscopy techniques revealed details about the final structure after fibril dissociation.

For the simulations, the researchers employed a technique that a few members of the current team had previously developed, called "nonequilibrium molecular dynamics (NEMD) simulations." Its results corroborated those of the experiment and additionally clarified the entire amyloid dissociation process down to very specific details. Through the simulations, the scientists observed that the process begins at the core of the fibril where the resonance breaks intermolecular hydrogen bonds and thus separates the proteins in the aggregate. The disruption to this structure then spreads outward to the extremities of the fibril.

Together, the experiment and simulation make a good case for a novel treatment possibility for neurodegenerative disorders. Dr Kawasaki remarks, "In view of the inability of existing drugs to slow or reverse the cognitive impairment in Alzheimer's disease, developing non-pharmaceutical approaches is very desirable. The ability to use infrared lasers to dissociate amyloid fibrils opens up a promising approach."

The team's long-term goal is to establish a framework combining laser experiments with NEMD simulations to study the process of fibril dissociation in even more detail, and new works are already underway. All these efforts will hopefully light a beacon of hope for those dealing with Alzheimer's or other neurodegenerative diseases.

https://www.sciencedaily.com/releases/2020/08/200804111501.htm

Baby boomers show concerning decline in cognitive functioning

Trend reverses progress over several generations, study finds

August 3, 2020

Science Daily/Ohio State University

In a reversal of trends, American baby boomers scored lower on a test of cognitive functioning than did members of previous generations, according to a new nationwide study.

Findings showed that average cognition scores of adults aged 50 and older increased from generation to generation, beginning with the greatest generation (born 1890-1923) and peaking among war babies (born 1942-1947).

Scores began to decline in the early baby boomers (born 1948-1953) and decreased further in the mid baby boomers (born 1954-1959).

While the prevalence of dementia has declined recently in the United States, these results suggest those trends may reverse in the coming decades, according to study author Hui Zheng, professor of sociology at The Ohio State University.

"It is shocking to see this decline in cognitive functioning among baby boomers after generations of increases in test scores," Zheng said.

"But what was most surprising to me is that this decline is seen in all groups: men and women, across all races and ethnicities and across all education, income and wealth levels."

Results showed lower cognitive functioning in baby boomers was linked to less wealth, along with higher levels of loneliness, depression, inactivity and obesity, and less likelihood of being married.

The study was published online recently in the Journals of Gerontology: Social Sciences.

Zheng analyzed data on 30,191 Americans who participated in the 1996 to 2014 Health and Retirement Survey, conducted by the University of Michigan. People over 51 years old were surveyed every two years.

As part of the study, participants completed a cognitive test in which they had to recall words they had heard earlier, count down from 100 by 7s, name objects they were shown and perform other tasks.

Other research has shown that overall rates of mortality and illness have increased in baby boomers, but generally found that the highly educated and wealthiest were mostly spared.

"That's why it was so surprising to me to see cognitive declines in all groups in this study," Zheng said. "The declines were only slightly lower among the wealthiest and most highly educated."

Zheng also compared cognition scores within each age group across generations so that scores are not skewed by older people who tend to have poorer cognition. Even in this analysis, the baby boomers came out on bottom.

"Baby boomers already start having lower cognition scores than earlier generations at age 50 to 54," he said.

The question, then, is what has happened to baby boomers? Zheng looked for clues across the lifetimes of those in the study.

Increasing cognition scores in previous generations could be tied to beneficial childhood conditions -- conditions that were similar for baby boomers, Zheng said.

Baby boomers' childhood health was as good as or better than previous generations and they came from families that had higher socioeconomic status. They also had higher levels of education and better occupations.

"The decline in cognitive functioning that we're seeing does not come from poorer childhood conditions," Zheng said.

The biggest factors linked to lower cognition scores among baby boomers in the study were lower wealth, higher levels of self-reported loneliness and depression, lack of physical activity and obesity.

Living without a spouse, being married more than once in their lives, having psychiatric problems and cardiovascular risk factors including strokes, hypertension, heart disease and diabetes were also associated with lower cognitive functioning among people in this generation.

"If it weren't for their better childhood health, move favorable family background, more years of education and higher likelihood of having a white-collar occupation, baby boomers would have even worse cognitive functioning," Zheng said.

There were not enough late baby boomers (born in 1960 or later) to include in this study, but Zheng said he believes they will fare no better. The same might be true for following generations unless we find a solution for the problems found here, he said.

While many of the problems linked to lower cognitive functioning are symptoms of modern life, like less connection with friends and family and growing economic inequality, other problems found in this study are unique to the United States, Zheng said. One example would be the lack of universal access and high cost of health care.

"Part of the story here are the problems of modern life, but it is also about life in the U.S.," he said.

One of the biggest concerns is that cognitive functioning when people are in their 50s and 60s is related to their likelihood of having dementia when they are older.

"With the aging population in the United States, we were already likely to see an increase in the number of people with dementia," Zheng said.

"But this study suggests it may be worse than we expected for decades to come."

https://www.sciencedaily.com/releases/2020/08/200803092125.htm

Memory loss reversed or abated in those with cognitive decline

July 31, 2020

Science Daily/IOS Press

Researchers sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

Latest research from Affirmativ Health succeeds in treating cognitive decline using personalized, precision medicine.

Affirmativ Health sought to determine whether a comprehensive and personalized program, designed to mitigate risk factors of Alzheimer's disease could improve cognitive and metabolic function in individuals experiencing cognitive decline. Findings provided evidence that this approach can improve risk factor scores and stabilize cognitive function.

July 31, 2020/Sonoma, CA Cognitive decline is a major concern of the aging population. Already, Alzheimer's disease affects approximately 5.4 million Americans and 30 million people globally. Without effective prevention and treatment, the prospects for the future are bleak. By 2050, it is estimated that 160 million people globally will have the disease, including 13 million Americans, leading to potential bankruptcy of the Medicare system. Unlike several other chronic illnesses, Alzheimer's disease is on the rise -- recent estimates suggest that Alzheimer's disease has become the third leading cause of death in the United States behind cardiovascular disease and cancer. Since its first description over 100 years ago, Alzheimer's disease has been without effective treatment. While researchers continue to seek out a cure, it is becoming clear that there are effective treatment options. More and more research supports the conclusion that Alzheimer's disease is not a disease of only Beta Amyloid plaques and Tao tangles but a complex and systemic disease. In this study of patients with varying levels of cognitive decline, it is demonstrated how a precision and personalized approach results in either stabilization or improvement in memory.

Interventions to stop the progression of Alzheimer's disease have been marginally successful at best. This study uses a more comprehensive, personalized approach addressing each participant's unique risk factors. "The findings, published in the Journal of Alzheimer's Disease Reports (Journal of Alzheimer's Disease Reports 4(1)), are encouraging and indicate that a more extensive clinical study is warranted," said Brian Kennedy, PhD, Director of The Centre for Healthy Aging, National University Health System, Singapore and Chief Scientific Officer, Affirmativ Health.

The Affirmativ Health scientific team, after thorough review of published research, has developed a comprehensive approach to addressing scientifically supported risk factors that have been rigorously defined as interventions to promote prevention, increased resiliency, and stabilization of brain function in the realm of AD and dementia. Utilizing cutting edge technology in concert with in-person coaching and consultation, we are demonstrating that a multi-modal and personalized approach promotes an improved resiliency and restoration of optimal brain function. The personalized therapeutic program includes genetics, an extensive blood panel, medical history and lifestyle data to evaluate relevant metabolic risk factors and nutrient levels associated with cognitive health. "Target laboratory levels differ from standard laboratory ranges as the goal is to reach optimized levels for cognitive health," Ginger Schechter, MD, Chief Medical Officer, Affirmativ Health

The study approach considers more than 35 factors known to contribute to cognitive decline. Results demonstrate that certain of those factors are more affected than others again demonstrating the need for a more precise treatment plan. "This study supports the need for an approach that focuses on a one-size fits one, not a one-size fits all, approach that comprehensively assesses all involved risk factors affecting memory loss," Denise M Kalos, CEO Affirmativ Health

In conjunction with the publication of this vital study, and to expose alternative treatment options for Alzheimer's disease and cognitive decline, the team at Affirmativ Health has written a book, Outsmart your Brain -- an Insider's Guide to Life-Long Memory. "Memory is not something that should diminish with age; you are never too young to start developing healthy habits that can ultimately impact your cognition," Outsmart Your Brain. This book leverages the foundation of Affirmativ Health's research to deliver a tips and tools guide for the maintenance of good cognitive health. "Far too few people understand how critical lifestyle and dietary choices are for brain function. 'Outsmart Your Brain' is an important tool to get this information into the hands of those who should know it, everyone!, in easy-to-understand language," Ryan R. Fortna, MD, PhD, Chief Medical/Scientific Officer, ADx Healthcare.

https://www.sciencedaily.com/releases/2020/07/200731104124.htm

Forty percent of dementia cases could be prevented or delayed by targeting 12 risk factors throughout life

July 30, 2020

Science Daily/University of Southern California - Health Sciences

Modifying 12 risk factors over a lifetime could delay or prevent 40% of dementia cases, according to an updated report by the Lancet Commission on dementia prevention, intervention and care presented at the Alzheimer's Association International Conference (AAIC 2020).

Twenty-eight world-leading dementia experts added three new risk factors in the new report -- excessive alcohol intake and head injury in mid-life and air pollution in later life. These are in addition to nine factors previously identified by the commission in 2017: less education early in life; mid-life hearing loss, hypertension and obesity; and smoking, depression, social isolation, physical inactivity and diabetes later in life (65 and up).

"We are learning that tactics to avoid dementia begin early and continue throughout life, so it's never too early or too late to take action," says commission member and AAIC presenter Lon Schneider, MD, co-director of the USC Alzheimer Disease Research Center's clinical core and professor of psychiatry and the behavioral sciences and neurology at the Keck School of Medicine of USC.

Dementia affects some 50 million people globally, a number that is expected to more than triple by 2050, particularly in low- and middle-income countries where approximately two-thirds of people with dementia live, according to the report. Women are also more likely to develop dementia than men.

However, in certain countries, such as the United States, England and France, the proportion of older people with dementia has fallen, probably in part due to lifestyle changes, demonstrating the possibility of reducing dementia through preventative measures, Schneider says.

Schneider and commission members recommend that policymakers and individuals adopt the following interventions:

• Aim to maintain systolic blood pressure of 130 mm Hg or less from the age of 40.

• Encourage use of hearing aids for hearing loss and reduce hearing loss by protecting ears from high noise levels.

• Reduce exposure to air pollution and second-hand tobacco smoke.

• Prevent head injury (particularly by targeting high-risk occupations).

• Limit alcohol intake to no more than 21 units per week (one unit of alcohol equals 10 ml or 8 g pure alcohol).

• Stop smoking and support others to stop smoking.

• Provide all children with primary and secondary education.

• Lead an active life into mid-life and possibly later life.

• Reduce obesity and the linked condition of diabetes.

The report also advocates for holistic, individualized and evidenced-based care for patients with dementia, who typically have more hospitalizations for conditions that are potentially manageable at home and are at greater risk for COVID-19. In addition, it recommends providing interventions for family caregivers who are at risk for depression and anxiety.

The commission members conducted a thorough investigation of all the best evidence in the field, including systematic literature reviews, meta-analyses and individual studies, to reach their conclusions.

https://www.sciencedaily.com/releases/2020/07/200730123651.htm

New blood test shows great promise in the diagnosis of Alzheimer's disease

July 29, 2020

Science Daily/Lund University

A new blood test demonstrated remarkable promise in discriminating between persons with and without Alzheimer's disease and in persons at known genetic risk may be able to detect the disease as early as 20 years before the onset of cognitive impairment, according to a large international study published today in the Journal of the American Medical Association (JAMA) and simultaneously presented at the Alzheimer's Association International Conference.

For many years, the diagnosis of Alzheimer's has been based on the characterization of amyloid plaques and tau tangles in the brain, typically after a person dies. An inexpensive and widely available blood test for the presence of plaques and tangles would have a profound impact on Alzheimer's research and care. According to the new study, measurements of phospho-tau217 (p-tau217), one of the tau proteins found in tangles, could provide a relatively sensitive and accurate indicator of both plaques and tangles -- corresponding to the diagnosis of Alzheimer's -- in living people.

"The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting."

Researchers evaluated a new p-tau217 blood test in 1,402 cognitively impaired and unimpaired research participants from well-known studies in Arizona, Sweden, and Colombia. The study, which was coordinated from Lund University in Sweden, included 81 Arizona participants in Banner Sun Health Research Institute's Brain Donation program who had clinical assessments and provided blood samples in their last years of life and then had neuropathological assessments after they died; 699 participants in the Swedish BioFINDER Study who had clinical, brain imaging, cerebrospinal fluid (CSF), and blood-based biomarker assessments; and 522 Colombian autosomal dominant Alzheimer's disease (ADAD)-causing mutation carriers and non-carriers from the world's largest ADAD cohort.

• In the Arizona (Banner Sun Health Research Institute) Brain Donation Cohort, the plasma p-tau217 assay discriminated between Arizona Brain donors with and without the subsequent neuropathological diagnosis of "intermediate or high likelihood Alzheimer's" (i.e., characterized by plaques, as well as tangles that have at least spread to temporal lobe memory areas or beyond) with 89% accuracy; it distinguished between those with and without a diagnosis of "high likelihood Alzheimer's" with 98% accuracy; and higher ptau217 measurements were correlated with higher brain tangle counts only in those persons who also had amyloid plaques.

• In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of Alzheimer's and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements; and it distinguished between those with and without an abnormal tau PET scan with 93% accuracy.

• In the Colombia Cohort, the assay began to distinguish between mutation carriers and non-carriers 20 years before their estimated age at the onset of mild cognitive impairment.

In each of these analyses, p-tau217 (a major component of Alzheimer's disease-related tau tangles) performed better than p-tau181 (another component of tau tangles and a blood test recently found to have promise in the diagnosis of Alzheimer's) and several other studied blood tests.

Other study leaders include Jeffrey Dage, PhD, from Eli Lilly and Company, who developed the p-tau217 assay, co-first authors Sebastian Palmqvist, MD, PhD, and Shorena Janelidz, PhD, from Lund University, and Eric Reiman, MD, Banner Alzheimer's Institute, who organized the analysis of Arizona and Colombian cohort data.

In the last two years, researchers have made great progress in the development of amyloid blood tests, providing valuable information about one of the two cardinal features of Alzheimer's. While more work is needed before the test is ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of Alzheimer's. It has the potential to advance the disease's research and care in other important ways.

"Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author on the study.

"While there's more work to do, I anticipate that their impact in both the research and clinical setting will become readily apparent within the next two years."

Alzheimer's is a debilitating and incurable disease that affects an estimated 5.8 million Americans age 65 and older. Without the discovery of successful prevention therapies, the number of U.S. cases is projected to reach nearly 14 million by 2050.

https://www.sciencedaily.com/releases/2020/07/200729114404.htm

Flu, pneumonia vaccinations tied to lower risk of Alzheimer's dementia

July 27, 2020

Science Daily/Alzheimer's Association

Flu (influenza) and pneumonia vaccinations are associated with reduced risk of Alzheimer's disease, according to new research reported at the Alzheimer's Association International Conference® (AAIC®) 2020.

Three research studies reported at AAIC 2020 suggest:

At least one flu vaccination was associated with a 17% reduction in Alzheimer's incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer's incidence.

Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer's risk by up to 40% depending on individual genes.

Individuals with dementia have a higher risk of dying (6-fold) after infections than those without dementia (3-fold).

"With the COVID-19 pandemic, vaccines are at the forefront of public health discussions. It is important to explore their benefit in not only protecting against viral or bacterial infection but also improving long-term health outcomes," said Maria C. Carrillo, Ph.D., Alzheimer's Association chief science officer.

"It may turn out to be as simple as if you're taking care of your health in this way -- getting vaccinated -- you're also taking care of yourself in other ways, and these things add up to lower risk of Alzheimer's and other dementias," Carrillo said. "This research, while early, calls for further studies in large, diverse clinical trials to inform whether vaccinations as a public health strategy decrease our risk for developing dementia as we age."

Seasonal Flu Vaccine May Reduce Incidence of Alzheimer's Dementia 

Previous research has suggested vaccinations may have a protective factor against cognitive decline, but there have been no large, comprehensive studies focused on the influenza (flu) vaccine and Alzheimer's disease risk, specifically. To address this gap, Albert Amran, a medical student at McGovern Medical School at The University of Texas Health Science Center at Houston, and team, investigated a large American health record dataset (n=9,066).

Amran and team found having one flu vaccination was associated with a lower prevalence of Alzheimer's (odds ratio 0.83, p<0.0001), and among vaccinated patients receiving the flu vaccine more frequently was associated with an even lower prevalence of Alzheimer's (odds ratio 0.87, p=0.0342). Thus, people that consistently got their annual flu shot had a lower risk of Alzheimer's. This translated to an almost 6% reduced risk of Alzheimer's disease for patients between the ages of 75-84 for 16 years.

The researchers found the protective association between the flu vaccine and the risk of Alzheimer's was strongest for those who received their first vaccine at a younger age -- for example, the people who received their first documented flu shot at age 60 benefitted more than those who received their first flu shot at age 70.

"Our study suggests that regular use of a very accessible and relatively cheap intervention -- the flu shot -- may significantly reduce risk of Alzheimer's dementia," Amran said. "More research is needed to explore the biological mechanism for this effect -- why and how it works in the body -- which is important as we explore effective preventive therapies for Alzheimer's."

Pneumonia Vaccine May Reduce Alzheimer's Risk Later in Life

Repurposing of existing vaccines may be a promising approach to Alzheimer's disease prevention. Svetlana Ukraintseva, Ph.D., Associate Research Professor in the Biodemography of Aging Research Unit (BARU) at Duke University Social Science Research Institute, and team, investigated associations between pneumococcal vaccination, with and without an accompanying seasonal flu shot, and the risk of Alzheimer's disease among 5,146 participants age 65+ from the Cardiovascular Health Study. The team also took into account a known genetic risk factor for Alzheimer's -- the rs2075650 G allele in the TOMM40 gene.

The researchers found that pneumococcal vaccination between ages 65-75 reduced risk of developing Alzheimer's by 25-30% after adjusting for sex, race, birth cohort, education, smoking, and number of G alleles. The largest reduction in the risk of Alzheimer's (up to 40%) was observed among people vaccinated against pneumonia who were non-carriers of the risk gene. Total number of vaccinations against pneumonia and the flu between ages 65 and 75 was also associated with a lower risk of Alzheimer's; however, the effect was not evident for the flu shot alone.

"Vaccinations against pneumonia before age 75 may reduce Alzheimer's risk later in life, depending on individual genotype," Ukraintseva said. "These data suggest that pneumococcal vaccine may be a promising candidate for personalized Alzheimer's prevention, particularly in non-carriers of certain risk genes."

Infection Substantially Increases Mortality in People with Dementia 

People living with dementia commonly experience other health conditions including viral, bacterial, and other infections. There is a growing trend in research to investigate whether infections might be worsening, more life-threatening or possibly causing dementia.

Janet Janbek, a Ph.D. student at the Danish Dementia Research Centre, Rigshospitalet and the University of Copenhagen in Denmark, and team, used data from national health registries to investigate mortality in Danish residents over age 65 (n=1,496,436) who had visited the hospital with an infection. They found that people with both dementia and such hospital visits died at a 6.5 times higher rate compared with people who had neither. Study participants with either dementia alone or infection-related contacts alone had a threefold increased rate. The rate of mortality was highest within the first 30 days following the hospital visit.

The researchers also found that for people living with dementia the mortality rates remained elevated for 10 years after the initial infection-related hospital visit, and mortality rates from all infections (including major infections like sepsis to minor ear infections) were higher compared with people without dementia or without an infection-related hospital visit.

"Our study supports the need to investigate these relations even further; to find out why infections are linked to higher mortality in people with dementia, specifically which risk factors and biological mechanisms are involved. This will help advance our understanding of the role of infections in dementia," said Janbek.

"Our study suggests that the health care system -- as well as relatives of people with dementia -- should have increased awareness of people with dementia who get infections, so they get the medical care they need. People with dementia require more specialized treatment even when their hospital visits are not directly due to their dementia but to what might appear to be an unrelated infection," Janbek added.

https://www.sciencedaily.com/releases/2020/07/200727114726.htm

What happens around an Alzheimer plaque?

July 22, 2020

Science Daily/VIB (the Flanders Institute for Biotechnology)

The brains of people living with Alzheimer's are riddled with plaques: protein aggregates consisting mainly of amyloid beta. Despite decades of research, the real contribution of these plaques to the disease process is still not clear. A research team led by Bart De Strooper and Mark Fiers at the VIB-KU Leuven Center for Brain & Disease Research in Leuven, Belgium used pioneering technologies to study in detail what happens in brain cells in the direct vicinity of plaques. Their findings, published in the prestigious journal Cell, show how different cell types in the brain work together to mount a complex response to amyloid plaques which is likely protective at first, but later on damaging to the brain.

The role of amyloid plaques in Alzheimer's disease has puzzled scientists ever since Alois Alzheimer first described them in the brain of a woman with young onset dementia. Now, over a century later, we have learned a lot about the molecular processes that lead to neurodegeneration and subsequent memory loss, but the relationship between the plaques and the disease process in the brain is still ambiguous.

"Amyloid plaques might act as a trigger or as a driver of disease, and the accumulation of amyloid beta in the brain likely initiates a complex multicellular neurodegenerative process," says professor Bart De Strooper (VIB-KU Leuven). His team set out to map the molecular changes that take place in cells near amyloid plaques.

"We used the latest technologies to analyze genome-wide transcriptomic changes induced by amyloid plaques in hundreds of small tissue domains," explains Mark Fiers, co-lead on the study. "In this way, we could generate a large data set of transcriptional changes that occur in response to increasing amyloid pathology, both in mouse and human brains."

Two co-expression networks

"We focused on the transcriptomic changes in the immediate neighborhood of the amyloid plaques, with a 50 micrometer perimeter," explains Wei-Ting Chen, a postdoc in De Strooper's team. In a well-studied genetic mouse model showing amyloid pathology, the scientists identified two novel gene co-expression networks that appeared highly sensitive to amyloid beta deposition.

Chen: "With increasing amyloid beta deposition, a multicellular co-expressed gene response was established encompassing no less than 57 plaque-induced genes." These genes were mainly expressed in astroglia and microglia, two types of supportive brain cells, and were not co-expressed in the absence of amyloid plaques.

"We also found interesting alterations in a second network, expressed mainly by another type of cells, namely oligodendrocytes," adds Ashley Lu, PhD student in the team. "This gene network was activated under mild amyloid stress but depleted in microenvironments with high amyloid accumulation."

"Many of the genes in both networks show similar alterations in human brain samples, strengthening our observations," adds Fiers.

Targeting plaques

"Our data demonstrate that amyloid plaques are not innocent bystanders of the disease, as has been sometimes suggested, but in fact induce a strong and coordinated response of all surrounding cell types," says De Strooper.

"Further work is needed to understand whether, and when, removal of amyloid plaques -- for instance by antibody therapy currently in development to treat amyloid plaques -- is sufficient to reverse these ongoing cellular processes."

Whether antibody binding to amyloid plaques could also modulate these glial responses remains to be determined. "It would in any case complicate the interpretation of the outcome of clinical trials as these cellular effects might be different between different antibodies," adds De Strooper.

https://www.sciencedaily.com/releases/2020/07/200722134916.htm

Physical stress on the job linked with brain and memory decline in older age

July 22, 2020

Science Daily/Colorado State University

A new study out of Colorado State University has found that physical stress in one's job may be associated with faster brain aging and poorer memory.

Aga Burzynska, an assistant professor in the Department of Human Development and Family Studies, and her research team connected occupational survey responses with brain-imaging data from 99 cognitively normal older adults, age 60 to 79. They found that those who reported high levels of physical stress in their most recent job had smaller volumes in the hippocampus and performed poorer on memory tasks. The hippocampus is the part of the brain that is critical for memory and is affected in both normal aging and in dementia.

Their findings were published this summer in Frontiers in Human Neuroscience under the research topic "Work and Brain Health Across the Lifespan."

"We know that stress can accelerate physical aging and is the risk factor for many chronic illnesses," Burzynska said. "But this is the first evidence that occupational stress can accelerate brain and cognitive aging."

She added that it is important to understand how occupational exposures affect the aging of our brains.

"An average American worker spends more than eight hours at work per weekday, and most people remain in the workforce for over 40 years," Burzynska said. "By pure volume, occupational exposures outweigh the time we spend on leisure social, cognitive and physical activities, which protect our aging minds and brains."

PHYSICAL DEMANDS AT WORK

Burzynska explained that the association between "physical stress" and brain/memory were driven by physical demands at work. These included excessive reaching, or lifting boxes onto shelves, not necessarily aerobic activity. This is important because earlier work by Burzynska and her colleagues showed that leisure aerobic exercise is beneficial for brain health and cognition, from children to very old adults. Therefore, the researchers controlled for the effects of leisure physical activity and exercise.

As expected, leisure physical activity was associated with greater hippocampal volume, but the negative association with physical demands at work persisted.

"This finding suggests that physical demands at work may have parallel yet opposing associations with brain health," Burzynska explained. "Most interventions for postponing cognitive decline focus on leisure, not on your job. It's kind of unknown territory, but maybe future research can help us make some tweaks to our work environment for long-term cognitive health."

She added that the results could have important implications for society.

"Caring for people with cognitive impairment is so costly, on economic, emotional and societal levels," Burzynska said. "If we can support brain health earlier, in middle-aged workers, it could have an enormous impact."

The researchers considered and corrected for several other factors that could be related to work environment, memory and hippocampus, such as age, gender, brain size, educational level, job title, years in the occupation and general psychological stress.

ONE PIECE OF THE PUZZLE

"The research on this topic is so fragmented," Burzynska said. "One previous study linked mid-life managerial experience with greater hippocampus volume in older age. Another showed that taxi drivers had larger hippocampi than a city's bus drivers, presumably due to the need to navigate. In our study, job complexity and psychological stress at work were not related to hippocampal volume and cognition. Clearly, our study is just one piece of the puzzle, and further research is needed."

The magnetic resonance imaging (MRI) data used for the study was collected at the University of Illinois Urbana-Champaign between 2011 and 2014.

CSU researchers now can collect MRI data with the new 3T scanner at the University's Translational Medicine Institute.

With this new capability, Burzynska, along with Michael Thomas and Lorann Stallones of CSU's Department of Psychology, is launching a new project, "Impact of Occupational Exposures and Hazards on Brain and Cognitive Health Among Aging Agricultural Workers," which will involve collecting MRI brain scans and identifying risk and protective factors that could help the agricultural community age successfully. The project recently obtained funding as an Emerging Issues Short-Term Project from the High Plains Intermountain Center for Agricultural Health and Safety.

https://www.sciencedaily.com/releases/2020/07/200722093448.htm