Regular crosswords and number puzzles linked to sharper brain in later life

May 16, 2019

Science Daily/University of Exeter

Older adults who regularly take part in word and number puzzles have sharper brains, according to the largest online study to date.

The more regularly adults aged 50 and over played puzzles such as crosswords and Sudoku, the better their brain function, according to research in more than 19,000 participants, led by the University of Exeter and King's College London.

The findings emerge from two linked papers published today (May 16th) in the International Journal of Geriatric Psychiatry. The researchers have previously presented their findings on word puzzles at the Alzheimer's Association International Conference in 2018. The new research builds on these findings and also reports the same effect in people who regularly complete number puzzles.

Researchers asked participants in the PROTECT study, the largest online cohort in older adults, to report how frequently they engage In word and number puzzles and undertake a series of cognitive tests sensitive to measuring changes in brain function. They found that the more regularly participants engaged with the puzzles, the better they performed on tasks assessing attention, reasoning and memory.

From their results, researchers calculate that people who engage in word puzzles have brain function equivalent to ten years younger than their age, on tests assessing grammatical reasoning and eight years younger than their age on tests measuring short term memory.

Dr Anne Corbett, of the University of Exeter Medical School, who led the research, said: "We've found that the more regularly people engage with puzzles such as crosswords and Sudoku, the sharper their performance is across a range of tasks assessing memory, attention and reasoning. The improvements are particularly clear in the speed and accuracy of their performance. In some areas the improvement was quite dramatic -- on measures of problem-solving, people who regularly do these puzzles performed equivalent to an average of eight years younger compared to those who don't. We can't say that playing these puzzles necessarily reduces the risk of dementia in later life but this research supports previous findings that indicate regular use of word and number puzzles helps keep our brains working better for longer."

The study used participants in the PROTECT online platform, run by the University of Exeter and Kings College London. Currently, more than 22,000 healthy people aged between 50 and 96 are registered in the study, and the study is expanding into other countries including Hong Kong and the US. The online platform enables researchers to conduct and manage large-scale studies without the need for laboratory visits. PROTECT is a 25 year study with participants being followed up annually to explore how the brain ages and what might influence the risk of dementia later in life. PROTECT is funded by the National Institute for Health Research (NIHR) Bioresource, including through its NIHR Clinical Research Network (CRN). In addition to taking part in vital research, participants in the PROTECT study have access to a brain training programme that has already been shown to benefit brain function, as well as having the opportunity to take part in exciting new research studies into brain health and dementia prevention.

Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said: "PROTECT is proving to be one of the most exciting research initiatives of this decade, allowing us to understand more about how the brain ages and to conduct cutting-edge new studies into how we can reduce the risk of dementia in people across the UK. If you're aged 50 or over, you could sign up to take part in research that will help us all maintain healthy brains as we age."

https://www.sciencedaily.com/releases/2019/05/190516082349.htm

Memories are strengthened via brainwaves produced during sleep

Researchers use medical imaging to map areas involved in recalling learned information while we slumber

May 15, 2019

Science Daily/Concordia University

Researchers have known about the close relationship between sleep and memory for decades. Now, a new study published in the journal NeuroImage looks at one important mechanism in that relationship. The research brings us closer to understanding how learned information turns into reliable memories during sleep.

The study was led by Thanh Dang-Vu, associate professor in the Department of Health, Kinesiology and Applied Physiology and Concordia University Research Chair in Sleep, Neuroimaging and Cognitive Health. In it, researchers studied how declarative information like facts and faces get stored after they have been learned. It has to do with brainwaves -- specifically, ones called sleep spindles, which are fast bursts of electrical activity produced by neurons mainly during Stage 2 sleep, prior to deep sleep.

Dang-Vu worked alongside Christophe Grova, associate professor in the Department of Physics, and researchers from the Cyclotron Research Centre at University of Liège in Belgium. Using medical imaging machines, they were able to assess brain activity related to these waves.

"It's hypothesized that sleep spindles play an important role in transferring information from the hippocampus to the neo-cortex," Dang-Vu says. "This has the effect of increasing the strength of memories."

To get the images they needed, Dang-Vu's team used both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). They applied these tools to a group of student volunteers during and after a lab-based face-sequencing task. The students were shown a series of faces and asked to identify the order in which they were shown. The researchers scanned them while they were learning the faces, while they were asleep and again when they woke up and had to recall the sequences.

Sleep spindles reactivated

 They then came back every day for a week and repeated the task without being scanned. After a week had elapsed, they had memorized the task, and were once again scanned during sleep and asked to recall the sequences.

"Our aim was to compare the sleep spindles from the night where the subjects learned the new information to the night where they didn't have any new information to learn but were exposed to the same stimulus with the same faces," Dang-Vu explains.

The researchers found that during spindles of the learning night, the regions of the brain that were instrumental in processing faces were reactivated. They also observed that the regions in the brain involved in memory -- especially the hippocampus -- were more active during spindles in the subjects who remembered the task better after sleep.

This reactivation during sleep spindles of the regions involved in learning and memory "falls in line with the theory that during sleep, you are strengthening memories by transferring information from the hippocampus to the regions of the cortex that are important for the consolidation of that specific type of information," he says.

Using non-invasive imaging to identify the mechanisms that strengthen memories can, he hopes, lead to improvements in our understanding of how memories work -- and can lead to improved interventions for people with sleep or memory issues.

https://www.sciencedaily.com/releases/2019/05/190515131750.htm

Brain stimulation improves working memory in adults

May 15, 2019

Science Daily/Duke Department of Neurology

Magnetic stimulation of the brain improves working memory, offering a new potential avenue of therapy for individuals living with Alzheimer's disease and other forms of dementia, according to new research from the Duke University School of Medicine.

Healthy younger and older adult participants who received a therapy called repetitive transcranial magnetic stimulation (rTMS) performed better on a memory task than during an rTMS-like placebo in the study, which was published here in PLoS One.

"This study relies on highly individualized parameters, from the selection of the stimulated target, based on fMRI activation, to the selection of the difficulty, titrated according to subjects' performance. Now that we have shown that these specific parameters can improve performance in healthy subjects, we will be able to extend it to populations with memory deficits," said Lysianne Beynel, PhD, a postdoctoral associate in the Department of Psychiatry and Behavioral Sciences.

Working memory is the process of recalling and then using relevant information while performing a task. It's a key component of day-to-day tasks like driving to a new location, making a recipe, or following instructions. Individuals with Alzheimer's disease, which will more than double by 2050, and other forms of dementia, experience progressive loss of working memory and other forms of cognition, leading to a greater risk of injury or death and reducing their ability to function without home care.

Twenty-nine young adults and 18 older adults completed the study, which involved trying to remember and then reproduce a series of letters in alphabetical order. The authors applied either online high-frequency (5Hz) rTMS, or a placebo-like sham over the left prefrontal cortex, an area on the brain responsible for higher executive function. Participants of all ages who received rTMS performed better than those who received the rTMS-like placebo.

"Interestingly, we only saw this effect during when participants were trying their hardest, suggesting a real use-it-or-lose it principle at work here," said co-author Simon W. Davis, PhD. "Contrary to much of what we hear, aging brains have a remarkable capability to remember past events and to use that information in a flexible manner. The brain stimulation applied in our study shows that older adults benefited just as much as the young."

https://www.sciencedaily.com/releases/2019/05/190515130256.htm

Older adults expect to lose brain power, but most don't ask doctors how to prevent dementia

Many in their 50s and early 60s buy supplements or do puzzles in hopes of protecting brain health, but may miss out on effective strategies

May 15, 2019

Science Daily/Michigan Medicine - University of Michigan

Many Americans in their 50s and early 60s are worried about declining brain health, especially if they have loved ones with memory loss and dementia, a new national poll finds. 

But while the majority of those polled say they take supplements or do puzzles in an effort to stave off brain decline, very few of them have talked with their doctors about evidence-based ways to prevent memory loss.

As a result, they may miss out on proven strategies to keep their brains sharp into their later years, says the poll team from the University of Michigan.

In all, nearly half of respondents to the National Poll on Healthy Aging felt they were likely to develop dementia as they aged, and nearly as many worried about this prospect. In reality, research suggests that less than 20 percent of people who have reached age 65 will go on to lose cognitive ability from Alzheimer's disease, vascular dementia or other conditions.

Despite the brain-related concerns of so many respondents, only five percent of the entire group, and 10 percent of those who said they had a family history of dementia, said they had talked with a healthcare provider about how to prevent memory problems.

At the same time, 73 percent said they do crossword puzzles or brain games, or take supplements, to try to keep their minds sharp. Neither strategy has been shown to have a beneficial effect by major research studies.

The poll, carried out by the U-M Institute for Healthcare Policy and Innovation with support from AARP and Michigan Medicine, U-M's academic medical center, asked 1,028 adults aged 50 to 64 a range of brain health questions.

"While many people in this age range expressed concerns about losing memory, and say they take active steps to prevent it, most haven't sought advice from medical professionals, who could help them understand which steps actually have scientific evidence behind them," says Donovan Maust, M.D., M.S., a U-M geriatric psychiatrist who helped design the poll and analyze the results. "Many people may not realize they could help preserve brain health by managing their blood pressure and blood sugar, getting more physical activity and better sleep, and stopping smoking."

Maust worked with poll director Preeti Malani, M.D., U-M dementia researcher Kenneth Langa, M.D., PhD, and the poll team.

Effects of experience

The team found stark differences in perceptions and viewpoints between the one-third of poll respondents who said they had a family history of dementia, or had served as a caregiver to a loved one with dementia, and those without such experience or family links.

For instance, 73 percent of those with a family history of dementia said they themselves were somewhat or very likely to develop the condition as they aged -- compared with just 32 percent of those with no family history. The gap between the two groups was nearly as large when the research team asked if poll respondents were worried about developing dementia later in life.

"Staying mentally sharp is the number one concern for older adults," says Alison Bryant, Ph.D., senior vice president of research for AARP. "According to the Global Council on Brain Health, people should concentrate on those things we know can improve brain health -- eating a healthy diet, getting adequate sleep, exercising, and socializing with friends and family."

Attitudes toward dementia research

Differences also emerged between those who had dementia in their families, and those without, when the researchers asked respondents if they'd consider taking part in dementia-related research.

Seventy-one percent of those with a family history of dementia said they'd be willing to give researchers a sample of their DNA, compared with 51 percent of the other respondents. Nearly twice as many of those with a family history said they'd take part in a test of a new medicine aimed at preventing dementia, or a new treatment for people diagnosed with dementia.

The poll also suggests that researchers searching for better ways to prevent, diagnose or treat dementia may have to work hard to attract participants. Thirty-nine percent of those who wouldn't be willing to give a DNA sample said it was because they didn't want their DNA to be stored in a repository. Similarly, 37 percent of those who said they wouldn't take part in studies of new prevention or treatment strategies expressed concerns about being a "guinea pig," and one-fifth worried about potential harms.

Healthy lives, healthy attitudes

The poll also shows that a greater percentage of adults in their 50s and early 60s who say they get adequate sleep and exercise, ate healthily and were active socially at least several times a week felt their memory was just as sharp now as it was when they were younger, compared to those who do not engage in these healthy behaviors as frequently.

But those who said their health was fair or poor, or who reported that they didn't often engage in healthy lifestyle practices, were much more likely to say that their memory had declined since their younger years. In all, 59 percent of those polled said their memory was slightly worse than it used to be.

"For anyone who wants to stay as sharp as possible as they age, the evidence is clear: focus on your diet, your exercise, your sleep and your blood pressure," says Malani. "Don't focus on worrying about what might happen, or the products you can buy that promise to help, but rather focus on what you can do now that research has proven to help."

A full report of the findings and methodology is available at http://www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.

https://www.sciencedaily.com/releases/2019/05/190515085452.htm

Good sleep quality and good mood lead to good working memory with age

May 11, 2019

Science Daily/University of California - Riverside

A team of psychologists has found strong associations between working memory -- a fundamental building block of a functioning mind -- and three health-related factors: sleep, age, and depressed mood. The team also reports that each of these factors is associated with different aspects of working memory.

Working memory is the part of short-term memory that temporarily stores and manages information required for cognitive tasks such as learning, reasoning, and comprehension. Working memory is critically involved in many higher cognitive functions, including intelligence, creative problem-solving, language, and action-planning. It plays a major role in how we process, use, and remember information.

The researchers, led by Weiwei Zhang, an assistant professor of psychology at the University of California, Riverside, found that age is negatively related to the "qualitative" aspect of working memory -- that is, how strong or how accurate the memory is. In other words, the older the person, the weaker and less precise the person's memory. In contrast, poor sleep quality and depressed mood are linked to a reduced likelihood of remembering a previously experienced event -- the "quantitative" aspect of working memory.

"Other researchers have already linked each of these factors separately to overall working memory function, but our work looked at how these factors are associated with memory quality and quantity -- the first time this has been done," Zhang said. "All three factors are interrelated. For example, seniors are more likely to experience negative mood than younger adults. Poor sleep quality is also often associated with depressed mood. The piecemeal approach used in previous investigations on these relationships -- examining the relationship between one of these health-related factors and working memory -- could open up the possibility that an observed effect may be influenced by other factors."

The researchers are the first to statistically isolate the effects of the three factors on working memory quantity and quality. Although all three factors contribute to a common complaint about foggy memory, they seem to behave in different ways and may result from potentially independent mechanisms in the brain. These findings could lead to future interventions and treatments to counteract the negative impacts of these factors on working memory.

Research results appear in the Journal of the International Neuropsychological Society.

The researchers performed two studies. In the first study, they sampled 110 college students for self-reported measures of sleep quality and depressed mood and their independent relationship to experimental measures of working memory. In the second study, the researchers sampled 31 members of a community ranging in age from 21 to 77 years. In this study, the researchers investigated age and its relationship to working memory.

"We are more confident now about how each one of these factors impacts working memory," Zhang said. "This could give us a better understanding of the underlying mechanism in age-related dementia. For the mind to work at its best, it is important that senior citizens ensure they have good sleep quality and be in a good mood."

https://www.sciencedaily.com/releases/2019/05/190511083929.htm

Unexpectedly big wins improve two kinds of memory

May 6, 2019

Science Daily/Brown University

Researchers have discovered that instances in which outcomes are better than expected -- finding an unexpectedly good parking spot, for example, or spotting a $20 bill on the sidewalk -- improves memories of specific events. This is in addition to the long-established role that unexpectedly good outcomes have in influencing what are called integrated memories.

Remembering where you parked your car this morning is an example of specific episodic memory, while remembering good places to park in general is an example of an integrated memory.

"Our new finding is that incidental, irrelevant details from specific events -- whether the tree I parked beside was a spruce or a maple -- are also strengthened by unexpectedly good outcomes," said Matt Nassar, an assistant professor of neuroscience at Brown University and the study's corresponding author. "This finding has potential ramifications for how people with depression remember things, which is a focus of our future research. We'd like to be able to develop potential therapies for patients, but we're not there yet."

Since reward-prediction error -- the formal name for that instances in which outcomes are better than expected -- involves the release of the neurotransmitter dopamine in a specific brain area, the findings unveil new implications for treating depression, which has been linked to imbalances in key neurotransmitters including serotonin, norepinephrine and dopamine.

This means that someone with depression may not encode positive memories as effectively as an individual without depression, said Nassar, who is affiliated with Brown's Carney Institute for Brain Science. And when someone with depression looks back on past events, they might remember the negative events better than the positive events, which has the potential to spur a negative feedback loop, he said.

For study co-author Daniel Dillon, a researcher at McLean Hospital and Harvard Medical School, exploring the clinical connection between depression and memory is the primary research focus. The findings were published on Monday, May 6, in the journal Nature Human Behaviour.

The research team's experiment comprised both a learning phase and a memory phase. For each round during the learning task, participants were shown a point value between 1 and 100, shown an image of a living or inanimate object, given the option to gamble on whether they would win the "coin-flip" by playing or passing, and then informed if they won or lost. If the participants lost the round, they lost 10 points; if they won the round, they received the previously conveyed points for the round. At the end of 160 rounds, participants' point totals were converted into a small amount of money, typically less than $5, Nassar said.

After the learning phase, participants were tested on their memory for the specific images they saw. The researchers found that participants were much better at remembering the specific image from rounds where they had a high likelihood of winning compared to high-value rounds or rounds they chose not to play. They were not informed that the specific image would be important. They were only told that the general category of the object (living or inanimate) would determine the probability they would win.

The experiment, which was partly the senior thesis project of Anthony Jang, an undergraduate who earned his bachelor's degree from Brown in 2015, included more than 250 participants recruited through Amazon Mechanical Turk, a platform for crowdsourced work that serves as a convenient option for recruiting many participants for experiments.

While some of the participants paid close attention to the value of each round and the probability of winning for each category, the results of other participants were far more random, Nassar said. The people who paid more attention during the gambling rounds did better during the memory portion of the experiment, which he was able to incorporate into his computational model of the participants' memories.

The researchers also found that participants were equally good at remembering specific images from high value rounds they won when they were tested 5 minutes after the learning task as when they were tested 24 hours later, after a period of memory consolidation. That finding that surprised Nassar.

"There's a really nice study from 2010 by Ingrid Bethus and colleagues where they clearly show in rodents that dopamine doesn't help memory performance shortly after the learning experience, but it has a huge effect at 24 hours," Nassar said. "We spent quite a bit of time trying to rectify our results with that study because they don't line up. The tasks were quite different, given the two species involved. In the future, we hope to get a task that is more comparable to figure out the source of the timing differences."

In addition to attempting to determine the source of the memory consolidation differences, members of the research team are planning to rerun the experiment with participants with depression to see if they exhibit any memory differences.

Also, Nassar will continue his work determining the neural circuits involved in connecting reward-prediction error to episodic memories as well as untangling the interaction between the episodic memory system and integrated memory system.

https://www.sciencedaily.com/releases/2019/05/190506111426.htm

Exercise may improve memory in heart failure patients

May 4, 2019

Science Daily/European Society of Cardiology

Two-thirds of patients with heart failure have cognitive problems, according to research presented today at EuroHeartCare 2019, a scientific congress of the European Society of Cardiology (ESC).1

Heart failure patients who walked further in a six-minute test, which shows better fitness, as well as those who were younger and more highly educated, were significantly less likely to have cognitive impairment. The results suggest that fitter patients have healthier brain function.

Study author Professor Ercole Vellone, of the University of Rome "Tor Vergata," Italy, said: "The message for patients with heart failure is to exercise. We don't have direct evidence yet that physical activity improves cognition in heart failure patients, but we know it improves their quality and length of life. In addition, studies in older adults have shown that exercise is associated with improved cognition -- we hope to show the same for heart failure patients in future studies."

The cognitive abilities that are particularly damaged in heart failure patients are memory, processing speed (time it takes to understand and react to information), and executive functions (paying attention, planning, setting goals, making decisions, starting tasks).

"These areas are important for memorising healthcare information and having the correct understanding and response to the disease process," said Professor Vellone. "For example, heart failure patients with mild cognitive impairment may forget to take medicines and may not comprehend that weight gain is an alarming situation that requires prompt intervention."

The study highlights that cognitive dysfunction is a common problem in patients with heart failure -- 67% had at least mild impairment. "Clinicians might need to adapt their educational approach with heart failure patients -- for example involving a family caregiver to oversee patient adherence to the prescribed treatment," said Professor Vellone.

The study used data from the HF-Wii study, which enrolled 605 patients with heart failure from six countries. The average age was 67 and 71% were male. The Montreal Cognitive Assessment test was used to measure cognitive function and exercise capacity was measured with the six-minute walk test.

Professor Vellone said: "There is a misconception that patients with heart failure should not exercise. That is clearly not the case. Find an activity you enjoy that you can do regularly. It could be walking, swimming, or any number of activities. There is good evidence that it will improve your health and your memory, and make you feel better."

https://www.sciencedaily.com/releases/2019/05/190504130301.htm

Mental disorders more common in people who live alone

May 1, 2019

Science Daily/PLOS

Living alone is positively associated with common mental disorders, regardless of age and sex, according to a study published May 1, 2019 in the open-access journal PLOS ONE by Louis Jacob from University of Versailles Saint-Quentin-en-Yvelines, France, and colleagues.

The proportion of people living alone has increased in recent years due to population aging, decreasing marriage rates and lowering fertility. Previous studies have investigated the link between living alone and mental disorders but have generally been conducted in elderly populations and are not generalizable to younger adults.

In the new study, researchers used data on 20,500 individuals aged 16-64 living in England who participated in the 1993, 2000, or 2007 National Psychiatric Morbidity Surveys. Whether a person had a common mental disorder (CMD) was assessed using the Clinical Interview Schedule-Revised (CIS-R), a questionnaire focusing on neurotic symptoms during the previous week. In addition to the number of people living in a household, data was available on factors including weight and height, alcohol dependence, drug use, social support, and loneliness.

The prevalence of people living alone in 1993, 2000, and 2007 was 8.8%, 9.8%, and 10.7%. In those years, the rates of CMD was 14.1%, 16.3%, and 16.4%. In all years, all ages, and both men and women, there was a positive association between living alone and CMD (1993 odds ratio 1.69; 2000 OR 1.63; 2007 OR 1.88). In different subgroups of people, living alone increased a person's risk for CMD by 1.39 to 2.43 times. Overall, loneliness explained 84% of the living alone-CMD association. The authors suggest that interventions which tackle loneliness might also aid the mental wellbeing of individuals living alone.

Jacob summarizes: "Living alone is positively associated with common mental disorders in the general population in England."

https://www.sciencedaily.com/releases/2019/05/190501141053.htm

A comprehensive map of how Alzheimer's affects the brain

Analysis of genes altered by the disease could provide targets for new treatments

May 1, 2019

Science Daily/Massachusetts Institute of Technology

MIT researchers have performed the first comprehensive analysis of the genes that are expressed in individual brain cells of patients with Alzheimer's disease. The results allowed the team to identify distinctive cellular pathways that are affected in neurons and other types of brain cells.

This analysis could offer many potential new drug targets for Alzheimer's, which afflicts more than 5 million people in the United States.

"This study provides, in my view, the very first map for going after all of the molecular processes that are altered in Alzheimer's disease in every single cell type that we can now reliably characterize," says Manolis Kellis, a professor of computer science and a member of MIT's Computer Science and Artificial Intelligence Laboratory and of the Broad Institute of MIT and Harvard. "It opens up a completely new era for understanding Alzheimer's."

The study revealed that a process called axon myelination is significantly disrupted in patients with Alzheimer's. The researchers also found that the brain cells of men and women vary significantly in how their genes respond to the disease.

Kellis and Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory, are the senior authors of the study, which appears in the May 1 online edition of Nature. MIT postdocs Hansruedi Mathys and Jose Davila-Velderrain are the lead authors of the paper.

Single-cell analysis

The researchers analyzed postmortem brain samples from 24 people who exhibited high levels of Alzheimer's disease pathology and 24 people of similar age who did not have these signs of disease. All of the subjects were part of the Religious Orders Study, a longitudinal study of aging and Alzheimer's disease. The researchers also had data on the subjects' performance on cognitive tests.

The MIT team performed single-cell RNA sequencing on about 80,000 cells from these subjects. Previous studies of gene expression in Alzheimer's patients have measured overall RNA levels from a section of brain tissue, but these studies don't distinguish between cell types, which can mask changes that occur in less abundant cell types, Tsai says.

"We wanted to know if we could distinguish whether each cell type has differential gene expression patterns between healthy and diseased brain tissue," she says. "This is the power of single-cell-level analysis: You have the resolution to really see the differences among all the different cell types in the brain."

Using the single-cell sequencing approach, the researchers were able to analyze not only the most abundant cell types, which include excitatory and inhibitory neurons, but also rarer, non-neuronal brain cells such as oligodendrocytes, astrocytes, and microglia. The researchers found that each of these cell types showed distinct gene expression differences in Alzheimer's patients.

Some of the most significant changes occurred in genes related to axon regeneration and myelination. Myelin is a fatty sheath that insulates axons, helping them to transmit electrical signals. The researchers found that in the individuals with Alzheimer's, genes related to myelination were affected in both neurons and oligodendrocytes, the cells that produce myelin.

Most of these cell-type-specific changes in gene expression occurred early in the development of the disease. In later stages, the researchers found that most cell types had very similar patterns of gene expression change. Specifically, most brain cells turned up genes related to stress response, programmed cell death, and the cellular machinery required to maintain protein integrity.

Sex differences

The researchers also discovered correlations between gene expression patterns and other measures of Alzheimer's severity such as the level of amyloid plaques and neurofibrillary tangles, as well as cognitive impairments. This allowed them to identify "modules" of genes that appear to be linked to different aspects of the disease.

"To identify these modules, we devised a novel strategy that involves the use of an artificial neural network and which allowed us to learn the sets of genes that are linked to the different aspects of Alzheimer's disease in a completely unbiased, data-driven fashion," Mathys says. "We anticipate that this strategy will be valuable to also identify gene modules associated with other brain disorders."

The most surprising finding, the researchers say, was the discovery of a dramatic difference between brain cells from male and female Alzheimer's patients. They found that excitatory neurons and other brain cells from male patients showed less pronounced gene expression changes in Alzheimer's than cells from female individuals, even though those patients did show similar symptoms, including amyloid plaques and cognitive impairments. By contrast, brain cells from female patients showed dramatically more severe gene-expression changes in Alzheimer's disease, and an expanded set of altered pathways.

"That's when we realized there's something very interesting going on. We were just shocked," Tsai says.

So far, it is unclear why this discrepancy exists. The sex difference was particularly stark in oligodendrocytes, which produce myelin, so the researchers performed an analysis of patients' white matter, which is mainly made up of myelinated axons. Using a set of MRI scans from 500 additional subjects from the Religious Orders Study group, the researchers found that female subjects with severe memory deficits had much more white matter damage than matched male subjects.

More study is needed to determine why men and women respond so differently to Alzheimer's disease, the researchers say, and the findings could have implications for developing and choosing treatments.

"There is mounting clinical and preclinical evidence of a sexual dimorphism in Alzheimer's predisposition, but no underlying mechanisms are known. Our work points to differential cellular processes involving non-neuronal myelinating cells as potentially having a role. It will be key to figure out whether these discrepancies protect or damage the brain cells only in one of the sexes -- and how to balance the response in the desired direction on the other," Davila-Velderrain says.

The researchers are now using mouse and human induced pluripotent stem cell models to further study some of the key cellular pathways that they identified as associated with Alzheimer's in this study, including those involved in myelination. They also plan to perform similar gene expression analyses for other forms of dementia that are related to Alzheimer's, as well as other brain disorders such as schizophrenia, bipolar disorder, psychosis, and diverse dementias. 

https://www.sciencedaily.com/releases/2019/05/190501131400.htm

How the olfactory brain affects memory

April 29, 2019

Science Daily/Ruhr-University Bochum

How sensory perception in the brain affects learning and memory processes is far from fully understood. Two neuroscientists of Ruhr-Universität Bochum (RUB) have discovered a new aspect of how the processing of odours impacts memory centres. They showed that the piriform cortex -- a part of the olfactory brain -- has a direct influence on information storage in our most important memory structure, the hippocampus. Dr. Christina Strauch and Professor Denise Manahan-Vaughan report about their findings in the online edition of the magazine Cerebral Cortex on 9 April 2019.

Electric impulses simulate odours

To find out how odours affect memory formation, the researchers triggered an artificial perception of an odour in the brains of rats. To do this, they stimulated the piriform cortex with electrical impulses. "We were very surprised to see that the hippocampus directly responds to stimulation of the piriform cortex," remarked Christina Strauch.

The hippocampus uses sensory information to create complex memories. The basis of this processes is its ability to increase the efficacy of information transmission across synapses and thereby store memory contents. This process is called synaptic plasticity. Manahan-Vaughan and Strauch were the first to show that stimulation of the anterior piriform cortex triggers synaptic plasticity in the hippocampus.

Special role for olfaction

In a second step, the researchers examined to what extent the piriform cortex competes with the entorhinal cortex in driving hippocampal synaptic plasticity. This structure sends information about activity in all sensory modalities to the hippocampus. Activating the afferent pathway of this structure, called the perforant path, triggered completely different reaction patterns in the hippocampus, to those generated by the piriform cortex. "The study gives us a theoretical basis for understanding how olfaction plays such a special role in memory formation and retrieval," commented Denise Manahan-Vaughan.

https://www.sciencedaily.com/releases/2019/04/190429125422.htm