Brain-belly connection: Gut health may influence likelihood of developing Alzheimer's

May 11, 2023

Science Daily/University of Nevada, Las Vegas

Could changing your diet play a role in slowing or even preventing the development of dementia? We're one step closer to finding out, thanks to a new UNLV study that bolsters the long-suspected link between gut health and Alzheimer's disease.

The analysis -- led by a team of researchers with the Nevada Institute of Personalized Medicine (NIPM) at UNLV and published this spring in the Nature journal Scientific Reports -- examined data from dozens of past studies into the belly-brain connection. The results? There's a strong link between particular kinds of gut bacteria and Alzheimer's disease.

Between 500 and 1,000 species of bacteria exist in the human gut at any one time, and the amount and diversity of these microorganisms can be influenced by genetics and diet.

The UNLV team's analysis found a significant correlation between 10 specific types of gut bacteria and the likelihood of developing Alzheimer's disease. Six categories of bacteria -- Adlercreutzia, Eubacterium nodatum group, Eisenbergiella, Eubacterium fissicatena group, Gordonibacter, and Prevotella9 -- were identified as protective, and four types of bacteria -- Collinsella, Bacteroides, Lachnospira, and Veillonella -- were identified as a risk factor for Alzheimer's disease.

Certain bacteria in humans' guts can secrete acids and toxins that thin and seep through the intestinal lining, interact with the APOE(a gene identified as a major risk factor for Alzheimer's disease), and trigger a neuroinflammatory response -- affecting brain health and numerous immune functions, and potentially promoting development of the neurodegenerative disorder.

Researchers said their novel discovery of the distinct bacterial groups associated with Alzheimer's disease provides new insights into the relationship between gut microbiota and the world's most common form of dementia. The findings also advance scientists' understanding of how an imbalance of that bacteria may play a role in the disorder's development.

"Most of the microorganisms in our intestines are considered good bacteria that promote health, but an imbalance of those bacteria can be toxic to a person's immune system and linked to various diseases, such as depression, heart disease, cancer, and Alzheimer's disease," said UNLV research professor Jingchun Chen. "The take-home message here is that your genes not only determine whether you have a risk for a disease, but they can also influence the abundance of bacteria in your gut."

While their analysis established overarching categories of bacteria typically associated with Alzheimer's disease, the UNLV team said further research is needed to drill down into the specific bacterial species that influence risk or protection.

The hope is to one day develop treatments that are customized for an individual patient and their genetic makeup, such as medications or lifestyle change. Studies have shown that changes in gut microbiome through probiotic use and dietary adjustments can positively impact the immune system, inflammation, and even brain function.

"With more research it would be possible to identify a genetic trajectory that could point to a gut microbiome that would be more or less prone to developing diseases such as Alzheimer's," said study lead author and UNLV graduate student Davis Cammann, "but we also have to remember that the gut biome is influenced by many factors including lifestyle and diet."

https://www.sciencedaily.com/releases/2023/05/230511164633.htm

Deep sleep may mitigate Alzheimer's memory loss

May 4, 2023

Science Daily/University of California - Berkeley

A deep slumber might help buffer against memory loss for older adults facing a heightened burden of Alzheimer's disease, new research from the University of California, Berkeley, suggests.

Deep sleep, also known as non-REM slow-wave sleep, can act as a "cognitive reserve factor" that may increase resilience against a protein in the brain called beta-amyloid that is linked to memory loss caused by dementia. Disrupted sleep has previously been associated with faster accumulation of beta-amyloid protein in the brain. However, the new research from a team at UC Berkeley reveals that superior amounts of deep, slow-wave sleep can act as a protective factor against memory decline in those with existing high amounts of Alzheimer's disease pathology -- a potentially significant advance that experts say could help alleviate some of dementia's most devastating outcomes.

"With a certain level of brain pathology, you're not destined for cognitive symptoms or memory issues," said Zsófia Zavecz, a postdoctoral researcher at UC Berkeley's Center for Human Sleep Science. "People should be aware that, despite having a certain level of pathology, there are certain lifestyle factors that will help moderate and decrease the effects.

"One of those factors is sleep and, specifically, deep sleep."

The research, published Wednesday in the journal BMC Medicine, is the latest in a large body of work aimed at finding a cure for Alzheimer's disease and preventing it altogether.

As the most prevalent form of dementia, Alzheimer's disease destroys memory pathways and, in advanced forms, interferes with a person's ability to perform basic daily tasks. Roughly one in nine people over age 65 have the progressive disease -- a proportion that is expected to grow rapidly as the baby boomer generation ages.

In recent years, scientists have probed the ways that deposits of beta-amyloid associate with Alzheimer's disease and how such deposits also affect memory more generally. In addition to sleep being a foundational part of memory retention, the team at UC Berkeley previously discovered that the declining amount of a person's deep sleep could act as a "crystal ball" to forecast a faster rate of future beta-amyloid buildup in the brain, after which dementia is more likely set in.

Years of education, physical activity and social engagement are widely believed to shore up a person's resilience to severe brain pathology -- essentially keeping the mind sharp, despite the decreased brain health. These are called cognitive reserve factors. However, most of them, such as past years of education or the size of one's social network, cannot be easily changed or modified retroactively.

That idea of cognitive reserve became a compelling target for sleep researchers, said Matthew Walker, a UC Berkeley professor of neuroscience and psychology and senior author of the study.

"If we believe that sleep is so critical for memory," Walker said, "could sleep be one of those missing pieces in the explanatory puzzle that would tell us exactly why two people with the same amounts of vicious, severe amyloid pathology have very different memory?"

"If the findings supported the hypothesis, it would be thrilling, because sleep is something we can change," he added. "It is a modifiable factor."

To test that question, the researchers recruited 62 older adults from the Berkeley Aging Cohort Study. Participants, who were healthy adults and not diagnosed with dementia, slept in a lab while researchers monitored their sleep waves with an electroencephalography (EEG) machine. Researchers also used a positron emission tomography (PET) scan to measure the amount of beta-amyloid deposits in the participants' brains. Half of the participants had high amounts of amyloid deposits; the other half did not.

After they slept, the participants completed a memory task involving matching names to faces.

Those with high amounts of beta-amyloid deposits in their brain who also experienced higher levels of deep sleep performed better on the memory test than those with the same amount of deposits but who slept worse. This compensatory boost was limited to the group with amyloid deposits. In the group without pathology, deep sleep had no additional supportive effect on memory, which was understandable as there was no demand for resilience factors in otherwise intact cognitive function.

In other words, deep sleep bent the arrow of cognition upward, blunting the otherwise detrimental effects of beta-amyloid pathology on memory.

In their analysis, the researchers went on to control for other cognitive reserve factors, including education and physical activity, and still sleep demonstrated a marked benefit. This suggests that sleep, independent of these other factors, contributes to salvaging memory function in the face of brain pathology. These new discoveries, they said, indicate the importance of non-REM slow-wave sleep in counteracting some of the memory-impairing effects of beta-amyloid deposits.

Walker likened deep sleep to a rescue effort.

"Think of deep sleep almost like a life raft that keeps memory afloat, rather than memory getting dragged down by the weight of Alzheimer's disease pathology," Walker said. "It now seems that deep NREM sleep may be a new, missing piece in the explanatory puzzle of cognitive reserve. This is especially exciting because we can do something about it. There are ways we can improve sleep, even in older adults."

Chief among those areas for improvement? Stick to a regular sleep schedule, stay mentally and physically active during the day, create a cool and dark sleep environment and minimize things like coffee late in the day and screen time before bed. A warm shower before turning in for the night has also been shown to increase the quality of deep, slow-wave sleep, Zavecz said.

With a small sample size of healthy participants, the study is simply an early step in understanding the precise ways sleep may forestall memory loss and the advance of Alzheimer's, Zavecz said.

Still, it opens the door for potential longer-term experiments examining sleep-enhancement treatments that could have far-reaching implications.

"One of the advantages of this result is the application to a huge population right above the age of 65," Zavecz said. "By sleeping better and doing your best to practice good sleep hygiene, which is easy to research online, you can gain the benefit of this compensatory function against this type of Alzheimer's pathology."

https://www.sciencedaily.com/releases/2023/05/230504094948.htm

Air pollution may increase risk of dementia, complicated by genetics

May 2, 2023

Science Daily/University of California - San Diego

Three years ago, an international study commissioned by the journal Lancet listed 12 modifiable factors that increased the risk of dementia, including three new ones: excessive alcohol, head injury and air pollution.

Writing in the May 2, 2023 issue of the Journal of Alzheimer's Disease, a team of researchers, led by scientists at University of California San Diego, further elaborate on how exposure to the last of those new factors -- ambient air pollution, such as car exhaust and power plant emissions -- is associated with a measurably greater risk of developing dementia over time.

Senior author William S. Kremen, PhD, professor of psychiatry and co-director of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine, and colleagues examined baseline cognitive assessments of approximately 1,100 men participating in the ongoing Vietnam Era Twin Study of Aging. Average baseline age was 56, with 12 years of follow up.

They additionally looked at measures of exposure to particular matter (PM2.5) in the air and nitrogen dioxide (NO2), which is created when fossil fuels are burned, and assessments of episodic memory, executive function, verbal fluency, brain processing speed and APOE genotype.

APOE is a gene that provides instructions for making a protein crucial to the transport of cholesterol and other fats in the bloodstream. One version or allele of APOE called APOE-4 has been identified as a strong risk factor gene for Alzheimer's disease.

The researchers found that participants with higher levels of exposure to PM2.5 and NO2 in their 40s and 50s displayed worse cognitive functioning in verbal fluency from age 56 to 68. And persons with the APOE-4 allele appeared even more sensitive, with those exposed to higher PM2.5 levels showing worse outcomes for executive function and those with higher NO2 exposure showing worse outcomes involving episodic memory.

Executive function refers to higher-level cognitive skills used to plan, control and coordinate mental behaviors and acts. Episodic memory is the ability to recall and re-experience distinct, specific past events.

"The 2020 Lancet report concluded that modifying 12 risk factors, which include others like education and depression at midlife, could reduce dementia incidence by as much as 40%," said first author Carol E. Franz, PhD, professor of psychiatry and co-director of the Center for Behavior Genetics of Aging.

"That report placed ambient air pollution as a greater risk for Alzheimer's and related dementias than diabetes, physical activity, hypertension, alcohol consumption and obesity. Our findings underscore the importance of identifying modifiable risk factors as early in life as possible -- and that the processes by which air pollution affects risk for later-life cognitive decline begins earlier than previous studies suggest."

https://www.sciencedaily.com/releases/2023/05/230502155413.htm

60 years later, high school quality may have a long-term impact on cognition

May 2, 2023

Science Daily/Columbia University Irving Medical Center

A study of more than 2,200 adults who attended U.S. high schools in the early 1960s found that those who attended higher quality schools had better cognitive function 60 years later.

Previous studies have found that the number of years spent in school correlates with cognition later in life, but few studies have examined the impact of educational quality.

"Our study establishes a link between high-quality education and better late-life cognition and suggests that increased investment in schools, especially those that serve Black children, could be a powerful strategy to improve cognitive health among older adults in the United States," says Jennifer Manly, PhD, professor of neuropsychology at Columbia University Vagelos College of Physicians and Surgeons and senior author of the study.

The study, led by Manly and Dominika Šeblová, PhD, a postdoctoral research scientist at Columbia, used data from Project Talent, a 1960 survey of high school students across the United States, and follow-up data collected in the Project Talent Aging Study.

The researchers examined relationships between six indicators of school quality and several measures of cognitive performance in participants nearly 60 years after they left high school.

Since high-quality schools may be especially beneficial for people from disadvantaged backgrounds, the researchers also examined whether associations differed by geography, sex/gender, and race and ethnicity (the survey only included sufficient data from Black and white respondents).

Teacher training linked to late-life cognition in students

The researchers found that attending a school with a higher number of teachers with graduate training was the most consistent predictor of better later-life cognition, especially language fluency (for example, coming up with words within a category). Attending a school with a high number of graduate-level teachers was approximately equivalent to the difference in cognition between a 70-year-old and someone who is one to three years older. Other indicators of school quality were associated with some, but not all, measures of cognitive performance.

Manly and Šeblová say many reasons may explain why attending schools with well-trained teachers may affect later-life cognition. "Instruction provided by more experienced and knowledgeable teachers might be more intellectually stimulating and provide additional neural or cognitive benefits," Šeblová says, "and attending higher-quality schools may also influence life trajectory, leading to university education and greater earnings, which are in turn linked to better cognition in later life."

Greater impact on Black students

Though the associations between school quality and late-life cognition were similar between white and Black students, Black participants were more likely to have attended schools of lower quality.

"Racial equity in school quality has never been achieved in the United States and school racial segregation has grown more extreme in recent decades, so this issue is still a substantial problem," says Manly.

For example, a 2016 survey found that U.S schools attended by non-white students had twice as many inexperienced teachers as schools attended by predominantly white students.

"Racial inequalities in school quality may contribute to persistent disparities in late-life cognitive outcomes for decades to come," Manly adds.

Jennifer Manly, PhD, is a professor in the Department of Neurology, the Gertrude H. Sergievsky Center, and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University.

The findings were published May 2 in the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring in a paper titled "High school quality is associated with cognition 58 years later."

https://www.sciencedaily.com/releases/2023/05/230502090614.htm

Slowing down in your old age? It may be a dementia warning sign

It's generally accepted we will lose muscle strength and slow down as we age, but new research indicates this could also be a sign on a more sinister health concern of ageing.

May 1, 2023

Science Daily/Edith Cowan University

It's generally accepted we will lose muscle strength and slow down as we age, making it more difficult to perform simple tasks such as getting up, walking and sitting down.

But new Edith Cowan University (ECU) research indicates this could also be a signal for another sinister health concern of ageing: late-life dementia.

To investigate the relationship between muscle function and dementia, the research teams from ECU's Nutrition & Health Innovation Research Institute and Centre for Precision Health used data from the Perth Longitudinal Study of Ageing in Women to examine more than 1000 women with an average age of 75.

In collaboration with the University of Western Australia, the team measured the women's grip strength and the time it took for them to rise from a chair, walk three metres, turn around and sit back down -- known as a timed-up-and-go (TUG), test.

These tests were repeated after five years to monitor any loss of performance.

Over the next 15 years, almost 17 per cent of women involved in the study were found to have had a dementia event, categorised as a dementia-related hospitalisation or death.

The team found lower grip strength and slower TUG were significant risk factors for presenting with dementia, independent of genetic risk and lifestyle factors such as smoking, alcohol intake and physical activity levels.

Relationship established

The women with the weakest grip strength were found to be more than twice as likely to have a late-life dementia event than the strongest individuals.

A similar relationship emerged between TUG performance and dementia, with the slowest in their TUG test more than twice as likely to experience dementia than the quickest.

When researchers looked at the changes in grip strength and TUG test results after five years, a decrease in performance was also linked with greater dementia risk.

Those who had experienced the biggest decline in grip strength and TUG speed were approximately 2 and 2.5 times more likely, respectively, to have had a dementia event, compared to those in the group who recorded the smallest decline in performance.

Women with the biggest drop in TUG performance were found to be over four times more likely to have a dementia-related death than the fastest.

An early warning

Senior researcher Dr Marc Sim said grip strength, which can be easily measured using a handheld device known as a dynamometer, may be a measure of brain health due to the overlapping nature of cognitive and motor decline.

"Possibly due to a range of underlying similarities, grip strength may also present as a

surrogate measure of cardiovascular disease, inflammation and frailty, which are known risk factors for dementia," Dr Sim said.

Dr Sim said the findings from the study could help health professionals to identify dementia risk in patients earlier.

"Both grip strength and TUG tests aren't commonly performed in clinical practice, but both are inexpensive and simple screening tools," he said.

"Incorporating muscle function tests as part of dementia screening could be useful to identify high-risk individuals, who might then benefit from primary prevention programs aimed at preventing the onset of the condition such as a healthy diet and a physically active lifestyle.

"The exciting findings were that decline in these measures was associated with substantially higher risk, suggesting that if we can halt this decline, we may be able to prevent late-life dementias. However, further research is needed in this area."

Centre for Precision Health Director Professor Simon Laws said there has been encouraging progress in identifying early warning signs of dementia.

"We are now starting to see a number of simple yet indicative screening assessments that could be combined with other biological and clinical measures to provide a holistic risk-profile for individuals presenting to their GP with, for example, memory concerns," he said.

'Impaired muscle function, including its decline, is related to greater long-term late-life dementia risk in older women' was published in the Journal of Cachexia, Sarcopenia and Muscle.

https://www.sciencedaily.com/releases/2023/05/230501085855.htm

Study links nutrients, brain structure, cognition in healthy aging

April 25, 2023

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

In a new study, scientists explored the links between three measures known to independently predict healthy aging: nutrient intake, brain structure and cognitive function. Their analysis adds to the evidence that these factors jointly contribute to brain health in older adults.

Reported in the Journal of Nutrition, the study found that blood markers of two saturated fatty acids, along with certain omega-6, -7 and -9 fatty acids, correlated with better scores on tests of memory and with larger brain structures in the frontal, temporal, parietal and insular cortices. Watch a video about the research.

While other studies have found one-to-one associations between individual nutrients or classes of nutrients and specific brain regions or functions, very little research takes a comprehensive look at brain health, cognition and broad dietary patterns overall, said Aron Barbey, a professor of psychology, bioengineering and neuroscience at the University of Illinois Urbana-Champaign who led the study with postdoctoral researcher Tanveer Talukdar and psychology research scientist Chris Zwilling. The three co-authors all are affiliated with the Beckman Institute for Advanced Science and Technology at the U. of I.

"Our findings reveal that we can use nutrient biomarkers, cognitive tests and MRI measures of brain structure to account for much of the variation in healthy aging," Barbey said. "This allows us to better understand how nutrition contributes to health, aging and disease,"

The researchers collected data from 111 healthy older adults with MRI structural scans, blood-based biomarkers of 52 dietary nutrients and cognitive performance on tests of memory and intelligence. By combining these measures using a data-fusion approach, the team found associations between dozens of features that appear to work in tandem to promote brain and cognitive health in older adults.

Data-fusion allows researchers to look across multiple data sets to map traits or features that have common patterns of variability, said Talukdar, who tailored this method to incorporate the nutrition, cognition and brain volumetric data.

"We're looking at relationships among all of these together," he said. "This allows us to identify certain features that cluster together."

This overcomes some of the limitations of analyzing individual factors, Barbey said.

"If we just look at nutrition as it relates to brain structures and we don't study cognition, or if we look at nutrition as it relates to cognition and we don't study the brain, then we're actually missing really important pieces of information."

The most obvious features that clustered together in the new analysis involved the size of gray-matter volumes in the frontal, temporal and parietal cortices; performance on tests of auditory memory and short- and long-term memory; and blood markers related to consumption of monounsaturated and polyunsaturated fatty acids. Study participants who scored higher on the memory tests tended to have larger gray-matter volumes and higher levels of markers of omega-6, -7 and -9 fatty acids in their blood. Those who did more poorly on the cognitive tests also had smaller gray-matter volumes in those brain regions and lower levels of those dietary markers, the analysis revealed.

While the study only reveals associations between these factors and does not prove that dietary habits directly promote brain health, it adds to the evidence that nutrition is a key player in healthy aging, the researchers said.

"Our work motivates a more comprehensive picture of healthy aging," Zwilling said. This gives insight into the importance of diet and nutrition and the value of data-fusion methods for studying their contributions to adult development and the neuroscience of aging."

https://www.sciencedaily.com/releases/2023/04/230425205326.htm

Common infections linked to poorer cognitive performance in middle-aged and older adults

Findings, based on an analysis of 575 study participants, support the hypothesis that infections may negatively affect brain health

April 20, 2023

Science Daily/Johns Hopkins Bloomberg School of Public Health

A new study from a team led by researchers at the Johns Hopkins Bloomberg School of Public Health found that signs of common infections in a sample of middle-aged and older adults were associated with poorer performance on a test of global cognitive function.

The results add to a growing body of evidence suggesting that infections in mid- and late-life can worsen cognitive performance and may increase the risk of Alzheimer's disease and other dementias.

For their analysis, the researchers examined antibody levels to five common pathogens in 575 adults, ages 41 to 97. The adults were recruited from East Baltimore in 1981, as part of the Epidemiologic Catchment Area Study started that year by the National Institute of Mental Health. Baltimore study participants donated blood for testing and took cognitive tests during the same study period. Antibody tests for pathogens were conducted, including four herpes viruses -- herpes simplex virus type 1, cytomegalovirus, varicella zoster virus (chickenpox and shingles viruses), and Epstein-Barr virus -- and the parasite Toxoplasma gondii. The latter often spreads to humans from cat feces or from eating undercooked meat.

The research team compared participants' blood test results to their performance on the Mini-Mental State Examination -- a global cognitive test that assesses things like orientation, attention, verbal comprehension, memory, and visual perception -- and on a word recall task, which tested memory for a list of words after a 20-minute delay. The researchers found that elevated antibodies to either herpes simplex virus type 1 or cytomegalovirus were individually associated with worse performance on the global cognitive test. Further, participants with a higher number of positive antibody tests tended to miss a larger number of items on the global cognition test.

The study was published online April 7 in the journal Alzheimer's & Dementia.

"The idea that common infections could contribute to cognitive decline and perhaps Alzheimer's disease risk was once on the fringe and remains controversial, but due to findings like the ones from this study, it's starting to get more mainstream attention," says senior author Adam Spira, PhD, professor in the Bloomberg School's Department of Mental Health and a core faculty member of the Johns Hopkins Center on Aging and Health. "After accounting for participants' age, sex, race, and the largest genetic risk factor for Alzheimer's disease, the data in our study showed that a greater number of positive antibody tests related to five different infections was associated with poorer cognitive performance. To our knowledge, this kind of additive effect of multiple infections on performance on a cognitive test has not been shown before."

The cause of Alzheimer's disease remains unclear. Prior research has made the connection with infections, including studies linking herpes simplex virus type 1 and cytomegalovirus to greater Alzheimer's risk. There is also evidence that the protein fragment amyloid beta, which forms insoluble plaques in the brains of people with Alzheimer's, functions as an antimicrobial peptide, and is secreted at higher levels by brain cells in response to infections.

Since the 2003-2004 wave, ECA study researchers at Johns Hopkins have conducted periodic follow-up interviews in Baltimore, including standard cognitive tests and taking blood samples. The two most recent waves of the study, funded by the National Institute on Aging, have focused on Alzheimer's disease and related outcomes.

The pathogens assessed in the study are often encountered in childhood and are either cleared or turned into suppressed, latent infections. As such, the researchers considered significant levels of antibodies against them in the middle-aged and older study participants as likely indicators of their reactivation due to immune system weakening with age.

The study's first author, Alexandra Wennberg, PhD, who completed her doctoral training in Spira's research group, is currently a postdoctoral research associate at Sweden's Karolinska Institutet. The co-authors include faculty in the Johns Hopkins School of Medicine and collaborating scientists at the National Institute on Aging Intramural Research Program.

Co-author Brion Maher, PhD, a geneticist and professor in the Bloomberg School's Department of Mental Health, also analyzed the results for participants who had a common Alzheimer's risk factor, the Ɛ4 variant of the apolipoprotein-E (ApoE) gene. The link between positive antibody count and cognitive status was present in both the Ɛ4 and non-Ɛ4 groups, but was stronger in the non-Ɛ4 group.

"That was a surprise, finding a weaker link in the Ɛ4 group," says Maher. "It's something that should be followed up with larger studies."

Spira, Maher, and their team, with funding from the National Institute on Aging, are following up with analyses of the Baltimore ECA data from the 2016 to 2022 wave. The researchers will also be collecting another round of data from this cohort.

https://www.sciencedaily.com/releases/2023/04/230420110130.htm

Simple test may predict cognitive impairment long before symptoms appear

Science Daily/American Academy of Neurology

In people with no thinking and memory problems, a simple test may predict the risk of developing cognitive impairment years later, according to a study published in the April 19, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"There is increasing evidence that some people with no thinking and memory problems may actually have very subtle signs of early cognitive impairment," said study author Ellen Grober, PhD, of Albert Einstein College of Medicine in the Bronx, New York. "In our study, a sensitive and simple memory test predicted the risk of developing cognitive impairment in people who were otherwise considered to have normal cognition."

The study involved 969 people with an average age of 69 with no thinking or memory problems at the start of the study. They were given a simple memory test and were followed for up to 10 years.

The test includes two phases. For the study phase, people are shown four cards, each with drawings of four items. They are asked to identify the item belonging to a particular category. For example, participants would name the item "grapes" after being asked to identify a "fruit." For the test phase, participants are first asked to recall the items. This measures their ability to retrieve information. Then, for items they did not remember, they are given category cues. This phase measures memory storage.

The participants were divided into five groups, or stages zero through four, based on their test scores, as part of the Stages of Objective Memory Impairment (SOMI) system. Stage zero represents no memory problems. Stages one and two reflect increasing difficulty with retrieving memories which can precede dementia by five to eight years. These participants continue to be able to remember items when given cues. In the third and fourth stages, people cannot remember all the items even after they are given cues. These stages precede dementia by one to three years.

A total of 47% of the participants were in stage zero, 35% in stage one, 13% in stage two and 5% in stages three and four combined.

Of the participants, 234 people developed cognitive impairment.

After adjusting for age, sex, education and a gene that affects a person's risk of Alzheimer's disease, APOE4, researchers found when compared to people who were at SOMI stage zero, people at stages one and two were twice as likely to develop cognitive impairment. People who were at stages three and four were three times as likely to develop cognitive impairment.

After adjusting for biomarkers of Alzheimer's disease including brain amyloid plaques and tau tangles, the SOMI system continued to predict an increased risk of cognitive impairment.

Researchers estimated that after 10 years about 72% of those in the third and fourth stages would have developed cognitive impairment, compared to about 57% of those in the second stage, 35% in the first stage and 21% of those in stage zero.

"Our results support the use of the SOMI system to identify people most likely to develop cognitive impairment," said Grober. "Detecting cognitive impairment at its earliest stages is beneficial to researchers investigating treatments. It also could benefit those people who are found to be at increased risk by consulting with their physician and implementing interventions to promote healthy brain aging."

A limitation of the study was that most participants were white and well educated. Grober said more research is needed in larger and more diverse populations.

https://www.sciencedaily.com/releases/2023/04/230419201936.htm

Older adults may achieve same cognition as undergrads

Learning multiple tasks led to cognition improvements in older adults; improvements that got better as more time passed

April 19, 2023

Science Daily/University of California - Riverside

A set of recent studies demonstrates for the first time that learning multiple new tasks carries benefits for cognition long after the learning has been completed.

The finding affirms a long-held assertion of the lead researcher, Rachel Wu, who is an associate professor of psychology at UC Riverside. That is, older adults can learn new tasks and improve their cognition in the process, if they approach learning as a child does.

"Our findings provide evidence that simultaneously learning real-world skills can lead to long-term improvements in cognition during older adulthood," Wu and her colleagues wrote in a recently published paper in the journal Aging and Mental Health. "Overall, our findings promote the benefits of lifelong learning, namely, to improve cognitive abilities in older adulthood."

One year after they learned new skills, the older research subjects tested higher for certain cognitive tasks than prior to the learning. Consistently, the scores for cognitive functions increased on average by at least two to three times, sometimes more.

The first study had six participants, the second study, 27. The median age of the study subjects was 66 and 69 years old, respectively. To qualify for the study, participants had to be at least 55 years old, fluent in English, have normal or corrected-to-normal vision, and have no prior diagnosis of a cognitive impairment. Participants in this study completed classwork and homework for approximately 15 hours a week for three months, time constraints Wu said limited the number of eligible participants.

For both studies, the participants learned at least three new skills, such as Spanish, using an iPad, photography, painting, and music composition over three months in a UC Riverside classroom for older adults. Cognitive tests were administered in a research lab before the start of the classes, halfway through the classes, and after three months of classes. There were then follow-up tests at three months, six months, and one year after the end of the classes.

"The primary goal of the follow-up assessments was to determine if gains in cognitive abilities… would continue up to one year after the intervention," the authors wrote.

The cognitive measures included attention, inhibition, and short-term memory, which requires remembering small amounts of information needed to perform tasks, such as recalling a phone number or words from a list.

The overall cognitive scores at three months, six months, and one year after the intervention were significantly higher than before the intervention, more than three times higher by many measures. In fact, the more time that passed after the learning had ceased, the higher the scores grew.

"Remarkably, the cognitive scores increased to levels similar to undergraduates taking the same cognitive tests for the first time," Wu said. "Our finding of continuous cognitive growth in older adulthood is unique because most studies show only maintenance of cognitive abilities or cognitive decline over time."

The key to the difference, Wu surmises, is learning multiple tasks simultaneously in an encouraging environment, similar to what children experience.

"The time and energy commitment to do so was similar to a full undergraduate course load," Wu and her colleagues wrote in the paper, titled "One-year cognitive outcomes from a multiple real-world skill learning intervention with older adults."

For Wu, it is further affirmation of her past research, which demonstrated that older adults can learn by emulating the learning behaviors of children. Among other things, it means older adults must approach learning with an open mind, unafraid of criticism and failure, receptive to instruction, willing to learn multiple tasks at once, and with a belief they can improve with effort.

https://www.sciencedaily.com/releases/2023/04/230419162821.htm

How music can prevent cognitive decline

April 17, 2023

Science Daily/Université de Genève

Normal ageing is associated with progressive cognitive decline. But can we train our brain to delay this process? A team from the University of Geneva (UNIGE), HES-SO Geneva and EPFL has discovered that practicing and listening to music can alter cognitive decline in healthy seniors by stimulating the production of grey matter. To achieve these results, the researchers followed over 100 retired people who had never practiced music before. They were enrolled in piano and music awareness training for six months. These results open new prospects for the support of healthy ageing. They are reported in NeuroImage: Reports.

Throughout our lives, our brain remodels itself. Brain morphology and connections change according to the environment and the experiences, for instance when we learn new skills or overcome the consequences of a stroke. However, as we age, this ''brain plasticity'' decreases. The brain also loses grey matter, where our precious neurons are located. This is known as ''brain atrophy''.

Gradually, a cognitive decline appears. Working memory, at the core of many cognitive processes, is one of the cognitive functions suffering the most. Working memory is defined as the process in which we briefly retain and manipulate information in order to achieve a goal, such as remembering a telephone number long enough to write it down or translating a sentence from a foreign language.

A study led by the UNIGE, HES-SO Geneva, and EPFL revealed that music practice and active listening could prevent working memory decline. Such activities promoted brain plasticity, they were associated with grey matter volume increase. Positive impacts have also been measured on working memory. This study was conducted among 132 healthy retirees from 62 to 78 years of age. One of the conditions for participation was that they had not taken any music lessons for more than six months in their lives.

Practicing music vs. listening to music

''We wanted people whose brains did not yet show any traces of plasticity linked to musical learning. Indeed, even a brief learning experience in the course of one's life can leave imprints on the brain, which would have biased our results'', explains Damien Marie, first author of the study, a research associate at the CIBM Center for Biomedical Imaging, the Faculty of Medicine and the Interfaculty Center for Affective Sciences (CISA) of UNIGE, as well as at the Geneva School of Health Sciences.

The participants were randomly assigned to two groups, regardless of their motivation to play an instrument. The second group had active listening lessons, which focused on instrument recognition and analysis of musical properties in a wide range of musical styles. The classes lasted one hour. Participants in both groups were required to do homework for half an hour a day.

Positive effects on both groups

''After six months, we found common effects for both interventions. Neuroimaging revealed an increase in grey matter in four brain regions involved in high-level cognitive functioning in all participants, including cerebellum areas involved in working memory. Their performance increased by 6% and this result was directly correlated to the plasticity of the cerebellum,'' says Clara James, last author of the study, a privat-docent at the Faculty of Psychology and Educational Sciences of UNIGE, and full professor at the Geneva School of Health Sciences. The scientists also found that the quality of sleep, the number of lessons followed over the course of the intervention, and the daily training quantity, had a positive impact on the degree of improvement in performance.

However, the researchers also found a difference between the two groups. In the pianists, the volume of grey matter remained stable in the right primary auditory cortex -- a key region for sound processing, whereas it decreased in the active listening group. ''In addition, a global brain pattern of atrophy was present in all participants. Therefore, we cannot conclude that musical interventions rejuvenate the brain. They only prevent ageing in specific regions,'' says Damien Marie.

These results show that practicing and listening to music promotes brain plasticity and cognitive reserve. The authors of the study believe that these playful and accessible interventions should become a major policy priority for healthy ageing. The next step for the team is to evaluate the potential of these interventions in people with mild cognitive impairment, an intermediate stage between normal ageing and dementia.

https://www.sciencedaily.com/releases/2023/04/230417142520.htm

Kombucha to kimchi: Which fermented foods are best for your brain?

April 13, 2023

Science Daily/Microbiology Society

Many countries around the world have their own staple fermented foods which are ingrained into culture and diet. It can’t be a coincidence that this has happened again and again. It seems logical that fermented foods offer more than a method of preservation.? 

Diet can hugely impact your mental health and previous research has shown that some foods are particularly good at positively impacting your brain. Fermented foods are a source of tryptophan, an amino acid key to the production of serotonin, a messenger in the brain which influences several aspects of brain function, including mood. The foods may also contain other brain messengers (known as neurotransmitters) in their raw form. It’s no surprise then that research has shown that eating fermented foods may have various long- and short-term impacts on brain function, such as reducing stress. But which foods have the biggest impact on brain health?? 

Researchers at APC Microbiome, University College Cork, and Teagasc (Ireland’s Agriculture and Food Development Authority) in Moorepark, Cork, Ireland are currently working on a large study to finally answer this question. Ramya Balasubramanian and the team at APC compared sequencing data from over 200 foods from all over the world, looking for a variety of metabolites that are known to be beneficial to brain health.?? 

The study is still in it’s initial stages, but researchers are already surprised by preliminary results. Ramya explains, “I expected only a few fermented foods would show up, but out of 200 fermented foods, almost all of them showed the ability to exert some sort of potential to improve gut and brain health”. More research is needed to fully understand which groups of fermented foods have the greatest effects on the human brain, but results are showing an unexpected victor. 

“Fermented sugar-based products and fermented vegetable-based products are like winning the lottery when it comes to gut and brain health”, explains Ramya.  

“For all that we see on sugar-based products being demonised, fermented sugar takes the raw sugar substrate, and it converts it into a plethora of metabolites that can have a beneficial effect on the host. So even though it has the name ‘sugar’ in it, if you do a final metabolomic screen, the sugar gets used by the microbial community that's present in the food, and they get converted into these beautiful metabolites that are ready to be cherry picked by us for further studies.”? 

These further studies are what’s next for Ramya. She plans to put her top ranked fermented foods through rigorous testing using an artificial colon and various animal models to see how these metabolites affect the brain.?? 

Ramya hopes that the public can utilise these preliminary results and consider including fermented foods in their diet as a natural way of supporting their mental health and general well-being. 

https://www.sciencedaily.com/releases/2023/04/230413154458.htm

People who think positively about aging are more likely to recover memory

April 12, 2023

Science Daily/Yale School of Public Health

A Yale School of Public Health study has found that older persons with mild cognitive impairment (MCI), a common type of memory loss, were 30% more likely to regain normal cognition if they had taken in positive beliefs about aging from their culture, compared to those who had taken in negative beliefs.

Researchers also found that these positive beliefs also enabled participants to recover their cognition up to two years earlier than those with negative age beliefs.This cognitive recovery advantage was found regardless of baseline MCI severity.

"Most people assume there is no recovery from MCI, but in fact half of those who have it do recover. Little is known about why some recover while others don't. That's why we looked at positive age beliefs, to see if they would help provide an answer," said Becca Levy, professor of public health and of psychology and lead author of the study.

Levy predicted that positive age beliefs could play an important role in cognitive recovery because her previous experimental studies with older persons found that positive age beliefs reduced the stress caused by cognitive challenges, increased self-confidence about cognition, and improved cognitive performance.

The new study is the first to find evidence that a culture-based factor -- positive age beliefs -- contributes to MCI recovery. The study appeared in JAMA Network Open. Martin Slade, a biostatistician and lecturer in internal medicine at Yale, is co-author of the study.

Older persons in the positive age-belief group who started the study with normal cognition were less likely to develop MCI over the next 12 years than those in the negative age-belief group, regardless of their baseline age and physical health.

The National Institute on Aging funded this study. It had 1,716 participants aged 65 and above who were drawn from the Health and Retirement Study, a national longitudinal study.

"Our previous research has demonstrated that age beliefs can be modified; therefore, age-belief interventions at the individual and societal levels could increase the number of people who experience cognitive recovery," Levy said.

https://www.sciencedaily.com/releases/2023/04/230412131116.htm

Greater fat stores and cholesterol increase with brain volume, but beyond a certain point they are associated with faster brain aging

April 11, 2023

Science Daily/University of California - Santa Barbara

Among Indigenous, rural non-industrial populations inhabiting the tropical forests of lowland Bolivia, researchers report, there appears to be an optimal balance between levels of food consumption and exercise that maximizes healthy brain aging and reduces the risk of disease.

"We hypothesize that energy gain from food intake was positively associated with late life brain health in the physically active, food-limited world of our ancestors, but that obesity and other manifestations of a Western lifestyle now lead to greater cognitive aging and dementia in middle and older ages," said UC Santa Barbara professor of anthropology Michael Gurven, a senior co-author on a study that published in the Proceedings of the National Academy of Sciences.

For this paper, the researchers collaborated with the Tsimané and Mosetén tribes, two Indigenous populations that live along tributaries of the Amazon River that flow through lowland Bolivia. In comparison to urban post-industrialized populations, these groups have less reliable access to food and have to exert a lot of effort to get it. They also have less access to modern health care. Meanwhile, people in wealthy countries have largely grown accustomed to eating more and exercising less -- habits that are associated with decreased brain volumes and faster cognitive decline.

"We set out to compare rates of brain aging between U.S. and European populations, and two Indigenous Bolivian populations: the Tsimané, who have very low rates of heart disease and minimal dementia, and the Mosetén, who are culturally similar to the Tsimané but whose lifestyle has shifted away from subsistence," said Gurven, who co-directs the Tsimané Health and Life History Project, a two-decade NIH-funded longitudinal study of health and aging.

The researchers enrolled 1,165 Tsimané and Mosetén adults, aged 40-94 years, and provided them transportation from their remote villages to the closest hospital with a CT scanner. They then used methods developed by study co-author Andrei Irimia, an assistant professor in the USC Leonard Davis School of Gerontology, to accurately measure brain volume from the CT scans. They also measured the participants' body mass index, blood pressure, total blood cholesterol and other biomarkers of cardiometabolic health.

"We found the fastest brain aging in the U.S. and European cohorts," Gurven said. "It was slowest in Tsimané and intermediate in Mosetén." Rates of brain atrophy, or brain shrinking, are correlated with cognitive decline and risks of neurodegenerative diseases such as dementia and Alzheimer's. In addition to less brain atrophy, the researchers found improved cardiovascular health in the Indigenous groups compared to industrialized populations in the U.S. and Europe.

The environment of limited food availability plays a role in the brain and cardiovascular fitness of nonindustrial societies, according to Irimia, in that "humans historically spent a lot of time exercising out of necessity to find food and their brain aging profiles reflected this lifestyle."

Studying the Mosetén population illuminated key findings: as a "sister" population to the Tsimané, they share similar languages, ancestral history and agrarian lifestyle. However, the Mosetén have more exposure to modern technology, medicine, infrastructure and education. Based on the researchers' results, according to Gurven, "the Mosetén's lifestyle is more vulnerable to the chronic diseases of aging than among the Tsimane, but less so than in post-industrialized countries."

Among the Tsimané, BMI, adiposity and higher levels of "bad" cholesterol were associated with bigger brain volumes for age. This, however, may be due to individuals being more muscular, on average, than individuals in industrialized countries who have comparable BMIs. Only at the highest levels of BMI, adiposity and cholesterol -- closer to the levels more typically observed in the U.S. -- was brain volume compromised.

"Our analyses suggest that 'too much of a good thing,' or what we call the 'embarrassment of riches,' seems to be what's going on," Gurven explained. "Greater adiposity, blood cholesterol and other indicators of nutrient intake increase with brain volume, but only up to a point -- a 'sweet spot.' Not too little and not too much. Beyond the sweet spot, higher levels of adiposity and cholesterol are associated with a smaller brain volume -- faster brain aging. That's consistent with our current environment being mismatched to our evolved biology."

Co-author Hillard Kaplan, an anthropologist at Chapman University and a co-director of the Tsimané Health and Life History Project, agrees. "During our evolutionary past, more food and less calories spent in getting it resulted in improved health, well-being and ultimately higher reproductive success," he said. "This evolutionary history selected for psychological and physiological traits that made us desire extra food and less physical work, and with industrialization, those traits led us to overshoot the mark."

According to Gurven, the study implications carry a hint of optimism. "The same active lifestyle that leads to a healthy heart seems to also lead to a healthy brain, and well into your 70s," he said. "If people like the Tsimané and Mosetén have found a manageable life-long balance to stave off dementia, then there's hope for the rest of us."

https://www.sciencedaily.com/releases/2023/04/230411150510.htm

Air pollution may increase risk for dementia

April 5, 2023

Science Daily/Harvard T.H. Chan School of Public Health

Exposure to fine particulate air pollutants (PM2.5) may increase the risk of developing dementia, according to a new meta-analysis from Harvard T.H. Chan School of Public Health.

"This is a big step in providing actionable data for regulatory agencies and clinicians in terms of making sense of the state of the literature on this hugely important health topic. The results can be used by organizations like the Environmental Protection Agency, which is currently considering strengthening limits on PM2.5 exposure," said lead author Marc Weisskopf, Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology. "Our findings support the public health importance of such a measure."

The study is the first systematic review and meta-analysis to use the new Risk of Bias In Non-Randomized Studies of Exposure (ROBINS-E) tool, which addresses bias in environmental studies in greater detail than other assessment approaches. It also is the first to include newer studies that used "active case ascertainment," a method that involved screening of entire study populations followed by in-person evaluation for dementia among individuals who did not have dementia at baseline.

The study will be published online April 5, 2023, in The BMJ.

More than 57 million people worldwide are currently living with dementia, and estimates suggest that number will increase to 153 million by 2050. Up to 40% of these cases are thought to be linked to potentially modifiable risk factors, such as exposure to air pollutants.

Weisskopf and his co-authors, Elissa Wilker, researcher in the Harvard Chan-NIEHS Center for Environmental Health, and Marwa Osman, a doctoral student in the Biological Science in Public Health program, scanned more than 2,000 studies and identified 51 that evaluated an association between ambient air pollution and clinical dementia, all published within the last 10 years. Those studies were assessed for bias using ROBINS-E, and 16 of them met the criteria for the meta-analysis. The majority of the research was about PM2.5, with nitrogen dioxide and nitrogen oxide being the next most common pollutants studied. Of the studies used in the meta-analysis, nine used active case ascertainment.

The researchers found consistent evidence of an association between PM2.5 and dementia, even when annual exposure was less than the current EPA annual standard of 12 micrograms per cubic meter of air (μg/m3). In particular, among the studies using active case ascertainment, the researchers found a 17% increase in risk for developing dementia for every 2 μg/m3 increase in average annual exposure to PM2.5. They also found evidence suggesting associations between dementia and nitrogen oxide (5% increase in risk for every 10 μg/m3 increase in annual exposure) and nitrogen dioxide (2% increase in risk for every 10 μg/m3 increase in annual exposure), though the data was more limited.

The researchers noted that air pollution's estimated association with risk of dementia is smaller than that of other risk factors, such as education and smoking. However, because of the number of people exposed to air pollution, the population-level health implications could be substantial.

"Given the massive numbers of dementia cases, identifying actionable modifiable risk factors to reduce the burden of disease would have tremendous personal and societal impact," Weisskopf said. "Exposure to PM2.5 and other air pollutants is modifiable to some extent by personal behaviors -- but more importantly through regulation."

https://www.sciencedaily.com/releases/2023/04/230405214852.htm

A higher dose of magnesium each day keeps dementia at bay

March 23, 2023

Science Daily/Australian National University

More magnesium in our daily diet leads to better brain health as we age, according to scientists from the Neuroimaging and Brain Lab at The Australian National University (ANU).

The researchers say increased intake of magnesium-rich foods such as spinach and nuts could also help reduce the risk of dementia, which is the second leading cause of death in Australia and the seventh biggest killer globally.

The study of more than 6,000 cognitively healthy participants in the United Kingdom aged 40 to 73 found people who consume more than 550 milligrams of magnesium each day have a brain age that is approximately one year younger by the time they reach 55 compared with someone with a normal magnesium intake of about 350 milligrams a day.

"Our study shows a 41 per cent increase in magnesium intake could lead to less age-related brain shrinkage, which is associated with better cognitive function and lower risk or delayed onset of dementia in later life," lead author and PhD researcher Khawlah Alateeq, from the ANU National Centre for Epidemiology and Population Health, said.

"This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health."

It's believed the number of people worldwide who will be diagnosed with dementia is expected to more than double from 57.4 million in 2019 to 152.8 million in 2050, placing a greater strain on health and social services and the global economy.

"Since there is no cure for dementia and the development of pharmacological treatments have been unsuccessful for the past 30 years, it's been suggested that greater attention should be directed towards prevention," study co-author Dr Erin Walsh, who is also from ANU, said.

"Our research could inform the development of public health interventions aimed at promoting healthy brain ageing through dietary strategies."

The researchers say a higher intake of magnesium in our diets from a younger age may safeguard against neurodegenerative diseases and cognitive decline by the time we reach our 40s.

"The study shows higher dietary magnesium intake may contribute to neuroprotection earlier in the ageing process and preventative effects may begin in our 40s or even earlier," Ms Alateeq said.

"This means people of all ages should be paying closer attention to their magnesium intake.

"We also found the neuroprotective effects of more dietary magnesium appears to benefit women more than men and more so in post-menopausal than pre-menopausal women, although this may be due to the anti-inflammatory effect of magnesium."

Participants completed an online questionnaire five times over a period of 16 months. The responses provided were used to calculate the daily magnesium intake of participants and were based on 200 different foods with varying portion sizes. The ANU team focused on magnesium-rich foods such as leafy green vegetables, legumes, nuts, seeds and wholegrains to provide an average estimation of magnesium intake from the participants' diets.

https://www.sciencedaily.com/releases/2023/03/230323103415.htm

MIND and Mediterranean diets associated with fewer Alzheimer's plaques and tangles

March 8, 2023

Science Daily/American Academy of Neurology

People who eat diets rich in green leafy vegetables as well as other vegetables, fruits, whole grains, olive oil, beans, nuts and fish may have fewer amyloid plaques and tau tangles in their brain -- signs of Alzheimer's disease -- than people who do not consume such diets, according to a study published in the March 8, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The study examined how closely people followed the MIND and Mediterranean diets. While similar, the Mediterranean diet recommends vegetables, fruit, and three or more servings of fish per week while the MIND diet prioritizes green leafy vegetables like spinach, kale and collard greens along with other vegetables. The MIND diet also prioritizes berries over other fruit and recommends one or more servings of fish per week. Both the MIND and Mediterranean diet recommend small amounts of wine.

While this study shows an association of regularly consuming these diets with fewer Alzheimer's disease plaques and tangles, it does not establish a cause and effect relationship.

"These results are exciting -- improvement in people's diets in just one area -- such as eating more than six servings of green leafy vegetables per week, or not eating fried foods -- was associated with fewer amyloid plaques in the brain similar to being about four years younger," said study author Puja Agarwal, PhD, of RUSH University in Chicago. "While our research doesn't prove that a healthy diet resulted in fewer brain deposits of amyloid plaques, also known as an indicator of Alzheimer's disease, we know there is a relationship and following the MIND and Mediterranean diets may be one way that people can improve their brain health and protect cognition as they age."

The study involved 581 people with an average age of 84 at the time of diet assessment who agreed to donate their brains at death to advance research on dementia. Participants completed annual questionnaires asking how much they ate of food items in various categories.

The participants died an average of seven years after the start of the study. Right before death, 39% of participants had been diagnosed with dementia. When examined after death, 66% met the criteria for Alzheimer's disease.

At autopsy, researchers examined participants' brains to determine the amounts of amyloid plaques and tau tangles. Both are found in the brains of people with Alzheimer's disease but may also be found in the brains of older people with normal cognition. Researchers then looked back at the food questionnaires which were collected during follow-up and ranked the quality of diet for each person.

For the Mediterranean diet, there were 11 food categories. Participants were given a score of zero to 55, with higher scores if they adhered to the diet in these categories: whole grain cereals, fruits, vegetables, legumes, olive oil, fish and potatoes. They were given lower scores if they ate red meat, poultry and full-fat dairy products.

For the MIND diet, there were 15 categories. Participants were given a score of zero to 15, with one point each for 10 brain-healthy food groups including green leafy vegetables, other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil, and wine. They lost a point if they ate foods more than recommended in five unhealthy food groups, including red meats, butter and margarine, cheese, pastries and sweets, and fried and fast food.

Researchers then divided participants into three groups for each diet and compared those in the highest groups to those in the lowest groups. For the Mediterranean diet, people in the highest group had an average score of 35 while those in the lowest group had an average score of 26. For the MIND diet, the highest group had an average score of 9 while the lowest group had an average score of 6.

After adjusting for age at death, sex, education, total calorie intake and whether people had a gene linked to a greater risk of Alzheimer's disease, researchers found people who scored highest for adhering to the Mediterranean diet had average plaque and tangle amounts in their brains similar to being 18 years younger than people who scored lowest. Researchers also found people who scored highest for adhering to the MIND diet had average plaque and tangle amounts similar to being 12 years younger than those who scored lowest.

A MIND diet score one point higher corresponded to typical plaque amounts of participants who were 4.25 years younger in age.

When looking at single diet components, researchers found people who ate the highest amounts of green leafy vegetables, or seven or more servings per week, had plaque amounts in their brains corresponding to being almost 19 years younger than people who ate the fewest, with one or fewer servings per week.

"Our finding that eating more green leafy vegetables is in itself associated with fewer signs of Alzheimer's disease in the brain is intriguing enough for people to consider adding more of these vegetables to their diet," said Agarwal. "Future studies are needed to establish our findings further."

A limitation of the study was that participants were mostly white, non-Hispanic, and older so the results cannot be generalized to other populations.

https://www.sciencedaily.com/releases/2023/03/230308201051.htm

How heavy alcohol consumption increases brain inflammation

March 7, 2023

Science Daily/Scripps Research Institute

For people with alcohol use disorder (AUD), there is a constant, vicious cycle between changes to the brain and changes to behavior. AUD can alter signaling pathways in the brain; in turn, those changes can exacerbate drinking.

Now, scientists at Scripps Research have uncovered new details about the immune system's role in this cycle. They reported in the journal Brain, Behavior and Immunity on Feb. 28, 2023, that the immune signaling molecule interleukin 1β (IL-1β) is present at higher levels in the brains of mice with alcohol dependence. In addition, the IL-1β pathway takes on a different role in these animals, causing inflammation in critical areas of the brain known to be involved in decision-making.

"These inflammatory changes to the brain could explain some of the risky decision-making and impulsivity we see in people with alcohol use disorder," says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine and a professor of neuroscience at Scripps Research. "In addition, our findings are incredibly exciting because they suggest a potential way to treat alcohol use disorder with existing anti-inflammatory drugs targeting the IL-1β pathway."

AUD is characterized by uncontrolled and compulsive drinking, and it encompasses a range of conditions including alcohol abuse, dependence and binge drinking. Researchers have previously discovered numerous links between the immune system and AUD -- many of them centered around IL-1β. People with certain mutations in the gene that codes for the IL-1β molecule, for instance, are more prone to developing AUD. In addition, autopsies of people who had AUD have found higher levels of IL-1β in the brain.

"We suspected that IL-1β was playing a role in AUD, but the exact mechanisms in the brain have been unclear," says first author Florence Varodayan, PhD, an assistant professor at Binghamton University and former postdoctoral fellow in the Roberto lab.

In the new study, Roberto, Varodayan and their colleagues compared alcohol-dependent mice with animals drinking moderate or no alcohol at all. They discovered that the alcohol-dependent group had about twice as much IL-1β in the medial prefrontal cortex (mPFC), a part of the brain that plays a role in regulating emotions and behaviors.

The team then went on to show that IL-1β signaling in the alcohol-dependent group was not only increased, but also fundamentally different. In mice that had not been exposed to alcohol, as well as in mice that had drunk moderate amounts of alcohol, IL-1β activated an anti-inflammatory signaling pathway. In turn, this lowered levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), a signaling molecule known to regulate neural activity in the brain.

However, in alcohol-dependent mice, IL-1β instead activated pro-inflammatory signaling and boosted levels of GABA, likely contributing to some of the changes in brain activity associated with AUD. Notably, these changes in IL-1β signaling in the alcohol-dependent mice persisted even during alcohol withdrawal.

Drugs that block the activity of IL-1β are already approved by the U.S. Food and Drug Administration to treat rheumatoid arthritis and other inflammatory conditions. More work is needed to determine whether these existing drugs could have utility in treating AUD.

"We plan to follow up on this study with more work on exactly how targeting specific components of the IL-1β pathway might be useful in treating alcohol use disorder," says Roberto.

https://www.sciencedaily.com/releases/2023/03/230307073219.htm

Trouble falling asleep at bedtime or in the middle of the night? It could impact your risk for developing dementia

March 6, 2023

Science Daily/Elsevier

Adding to the growing body of evidence on sleep disturbances and cognitive impairment, new research finds significant links between three measures of sleep disturbance and the risk for developing dementia over a 10-year period. The results, reported in the American Journal of Preventive Medicine, published by Elsevier, associate sleep-initiation insomnia (trouble falling asleep within 30 minutes) and sleep medication use with higher risk for developing dementia. The investigators also found that people who reported having sleep-maintenance insomnia (trouble falling back to sleep after waking) were less likely to develop dementia over the course of the study.

"We expected sleep-initiation insomnia and sleep medication usage to increase dementia risk, but we were surprised to find sleep-maintenance insomnia decreased dementia risk," explained lead investigator Roger Wong, PhD, MPH, MSW, an Assistant Professor in the Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY, USA. "The motivation behind this research was prompted on a personal level. My father has been experiencing chronic sleep disturbances since the COVID-19 pandemic began, and I was concerned how this would affect his cognition in the future. After reading the existing literature, I was surprised to see mixed findings on the sleep-dementia relationship, so I decided to investigate this topic."

This research is novel because it is the first to examine how long-term sleep disturbance measures are associated with dementia risk using a nationally representative US older adult sample. Previous research has associated REM sleep behavior, sleep deprivation (less than five hours of sleep), and the use of short-acting benzodiazepines with cognitive decline. Their results for sleep-maintenance insomnia support other recent studies using smaller, separate data samples.

This study used 10 annual waves (2011?2020) of prospective data from the National Health and Aging Trends Study (NHATS), a longitudinal panel study that surveys a nationally representative sample of Medicare beneficiaries aged 65 years and older within the USA. This study included only people who were dementia-free at baseline in 2011.

There is no cure for dementia and recent pharmaceutical approaches to treat dementia have had limited success, pointing to the importance of preventive approaches to dementia. "By focusing on the variations in sleep disturbances, our findings can help to inform lifestyle changes that can reduce dementia risk," explained co-investigator Margaret Anne Lovier, MPH, Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.

While the mechanism for decreased dementia risk among those with sleep-maintenance insomnia is still unknown, the investigators theorize that greater engagement in activities that preserve or increase cognitive reserve may thereby decrease dementia risk.

Recent evidence indicates there is a higher prevalence of sleep disturbances among older adults than among other age groups. This could be attributed to a variety of factors including anxiety about the COVID-19 pandemic or warmer nights as a consequence of climate change.

"Older adults are losing sleep over a wide variety of concerns. More research is needed to better understand its causes and manifestations and limit the long-term consequences," added Dr. Wong. "Our findings highlight the importance of considering sleep disturbance history when assessing the dementia risk profile for older adults. Future research is needed to examine other sleep disturbance measures using a national longitudinal sample, whether these sleep-dementia findings hold true for specific dementia subtypes, and how certain sociodemographic characteristics may interact with sleep disturbances to influence dementia risk."

https://www.sciencedaily.com/releases/2023/03/230306143443.htm

Taking vitamin D could help prevent dementia

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study.

March 1, 2023

Science Daily/University of Exeter

Taking vitamin D supplements may help ward off dementia, according to a new, large-scale study.

Researchers at the University of Calgary's Hotchkiss Brain Institute in Canada and the University of Exeter in the UK explored the relationship between vitamin D supplementation and dementia in more than 12,388 participants of the US National Alzheimer's Coordinating Center, who had a mean age of 71 and were dementia-free when they signed up. Of the group, 37 per cent (4,637) took vitamin D supplements.

In the study, published in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, the team found that taking vitamin D was associated with living dementia-free for longer, and they also found 40 per cent fewer dementia diagnoses in the group who took supplements.

Across the entire sample, 2,696 participants progressed to dementia over ten years; amongst them, 2,017 (75%) had no exposure to vitamin D throughout all visits prior to dementia diagnosis, and 679 (25%) had baseline exposure.

Professor Zahinoor Ismail, of the University of Calgary and University of Exeter, who led the research, said: "We know that vitamin D has some effects in the brain that could have implications for reducing dementia, however so far, research has yielded conflicting results. Our findings give key insights into groups who might be specifically targeted for vitamin D supplementation. Overall, we found evidence to suggest that earlier supplementation might be particularly beneficial, before the onset of cognitive decline."

While Vitamin D was effective in all groups, the team found that effects were significantly greater in females, compared to males. Similarly, effects were greater in people with normal cognition, compared to those who reported signs of mild cognitive impairment -- changes to cognition which have been linked to a higher risk of dementia.

The effects of vitamin D were also significantly greater in people who did not carry the APOEe4 gene, known to present a higher risk for Alzheimer's dementia, compared to non-carriers. The authors suggest that people who carry the APOEe4 gene absorb vitamin D better from their intestine, which might reduce the vitamin D supplementation effect. However, no blood levels were drawn to test this hypothesis.

Previous research has found that low levels of vitamin D are linked to higher dementia risk. Vitamin D is involved in the clearance of amyloid in the brain, the accumulation of which is one of the hallmarks of Alzheimer's disease. Studies have also found that vitamin D may provide help to protect the brain against build-up of tau, another protein involved in the development of dementia.

Co-author Dr Byron Creese, at the University of Exeter, said: "Preventing dementia or even delaying its onset is vitally important given the growing numbers of people affected. The link with vitamin D in this study suggests that taking vitamin D supplements may be beneficial in preventing or delaying dementia, but we now need clinical trials to confirm whether this is really the case. The ongoing VitaMIND study at the University of Exeter is exploring this issue further by randomly assigning participants to either take vitamin D or placebo and examining changes in memory and thinking tests over time."

The VitaMIND study is run via PROTECT, an online study open to people aged 40 and over. In PROTECT annual questionnaires on detailed lifestyle factors combine with cognitive testing, to determine what keeps the brain sharp in later life. To find out more or to sign up, visit their website. In Canada, CAN-PROTECT, is a linked online study on aging, in people aged 40 and over, with an additional focus on caregiving in dementia.

https://www.sciencedaily.com/releases/2023/03/230301101511.htm

Fructose could drive Alzheimer's disease

An evolutionary foraging instinct that relied on the sugar fructose, may now be fueling the formation of Alzheimer's disease

February 13, 2023

Science Daily/University of Colorado Anschutz Medical Campus

An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer's disease (AD), according to researchers at the University of Colorado Anschutz Medical Campus.

The study, published recently in The American Journal of Clinical Nutrition, offers a new way of looking at a fatal disease characterized by abnormal accumulations of proteins in the brain that slowly erode memory and cognition.

"We make the case that Alzheimer's disease is driven by diet," said the study's lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

"A basic tenet of life is to assure enough food, water and oxygen for survival," the study said. "Much attention has focused on the acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs."

When threatened with the possibility of starvation, early humans developed a survival response which sent them foraging for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires focus, rapid assessment, impulsivity, exploratory behavior and risk taking. It is enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose, a kind of sugar, helps damp down these centers, allowing more focus on food gathering.

In fact, the researchers found the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals.

The researchers noted that fructose reduces blood flow to the brain's cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, blood flow increased around the visual cortex associated with food reward. All of this stimulated the foraging response.

"We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial," Johnson said. "But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD."

Johnson suspects the survival response, what he calls the `survival switch,' that helped ancient humans get through periods of scarcity, is now stuck in the `on' position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production.

Fructose produced in the brain can lead to inflammation and ultimately Alzheimer's disease, the study said. Animals given fructose show memory lapses, a loss in the ability to navigate a maze and inflammation of the neurons.

"A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in Alzheimer's disease," Johnson said. "You can find high fructose levels in the brains of people with Alzheimer's as well."

Johnson suspects that the tendency of some AD patients to wander off might be a vestige of the ancient foraging response.

The study said more research is needed on the role of fructose and uric acid metabolism in AD.

"We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease," Johnson said.

https://www.sciencedaily.com/releases/2023/02/230213113345.htm