Dementia risk increased in 50-year-olds with blood pressure below hypertension threshold

Blood pressure that was higher than normal but still below the usual threshold for treating hypertension puts 50-year-olds at increased risk of dementia

June 12, 2018

Science Daily/European Society of Cardiology

New findings from the long-running Whitehall II study of over 10,000 civil servants has found 50-year-olds who had blood pressure that was higher than normal but still below the threshold commonly used when deciding to treat the condition, were at increased risk of developing dementia in later life. This increased risk was seen even when the study participants did not have other heart or blood vessel-related problems, according to the research.

This increased risk was seen even when the study participants did not have other heart or blood vessel-related problems, according to the research, which is published in the European Heart Journal.

Although there have been previous studies that have linked raised blood pressure in midlife to an increased risk of dementia in later life, the term 'midlife' has been poorly defined and ranged from 35 to 68 years.

The first author of the paper, Dr Jessica Abell, post-doctoral research fellow at the French National Institute of Health and Medical Research in Paris (INSERM) and a research associate in dementia and epidemiology at University College London (UCL), UK, said: "Previous research has not been able to test the link between raised blood pressure and dementia directly by examining the timing in sufficient detail. In our paper we were able to examine the association at age 50, 60 and 70, and we found different patterns of association. This will have important implications for policy guidelines, which currently only use the generic term 'midlife'."

Participants in the Whitehall II study, who were aged between 35-55 in 1985, had their blood pressure measured in 1985, 1991, 1997 and 2003. Other medical information was also taken, such as age, sex, lifestyle behaviours (such as smoking and alcohol intake), and socio-demographic factors.

Among the 8,639 people analysed for this study, 32.5% of whom were women, 385 developed dementia by 2017. Those who had a systolic blood pressure of 130 mmHg or more at the age of 50 had a 45% greater risk of developing dementia than those with a lower systolic blood pressure at the same age. This association was not seen at the ages of 60 and 70, and diastolic blood pressure was not linked to dementia.*

The link between high blood pressure and dementia was also seen in people who had no heart or blood vessel-related conditions (cardiovascular disease) during the follow-up period; they had an increased risk of 47% compared to people with systolic blood pressure lower than 130 mm.

Guidelines from NICE (National Institute for Health and Care Excellence) in the UK and the European Society of Cardiology both give a threshold of 140/90 mmHg for hypertension, although 2017 guidelines from the American Heart Association, the American College of Cardiology and nine other health organisations lowered the threshold to 130/80 mmHg for all adults. Ideal blood pressure is considered to be between 90/60mmHg and 120/80mmHg.

Professor Archana Singh-Manoux, research professor at INSERM and honorary professor at UCL, who led the research, said: "Our work confirms the detrimental effects of midlife hypertension for risk of dementia, as suggested by previous research. It also suggests that at age 50, the risk of dementia may be increased in people who have raised levels of systolic blood pressure below the threshold commonly used to treat hypertension.

"Our analysis suggests that the importance of mid-life hypertension on brain health is due to the duration of exposure. So we see an increased risk for people with raised blood pressure at age 50, but not 60 or 70, because those with hypertension at age 50 are likely to be 'exposed' to this risk for longer." The average age at which the study participants developed dementia was 75.

Possible reasons for the link between raised blood pressure and dementia include the fact that high blood pressure is linked to silent or mini strokes (where symptoms often are not noticeable), damage to the white matter in the brain, which contains many of the brain's nerve fibres, and restricted blood supply to the brain. This damage may underlie the resulting decline in the brain's processes.

Dr Abell said: "It is important to emphasise that this is observational, population-level research and so these findings do not translate directly into implications for individual patients. Furthermore, there is considerable discussion on the optimal threshold for the diagnosis of hypertension. There is plenty of evidence to suggest that maintaining a healthy blood pressure in middle age is important for both your heart and your brain later in life. Anyone who is concerned about their blood pressure levels should consult their GP."

Limitations of the study include the fact that diagnosis of dementia was made by linking to electronic medical records that might miss milder cases of dementia; the researchers were not able to examine whether the association of hypertension was stronger with Alzheimer's disease or vascular dementia because of the small numbers in the study affected by dementia, and this requires further research; and the researchers do not know whether effective management of high blood pressure in people in mid-life might weaken the risk of later dementia.

"One of the strengths of this study was having repeat blood pressure measurements on the same people, which allowed us to examine their blood pressure status over an 18-year period. This is rare, since previous research has often used a single measure of hypertension," concluded Professor Singh-Manoux.

Notes

*Systolic blood pressure measures the pressure in your blood vessels when the heart beats. Diastolic blood pressure measures the pressure when the heart rests between beats. When blood pressure measurements are given, the systolic number is the higher number and the diastolic number is the lower number e.g. 120/80 mmHg. Pressure is measured in millimetres of mercury (mmHg).

https://www.sciencedaily.com/releases/2018/06/180612201805.htm

Better physical fitness and lower aortic stiffness key to slower brain aging

June 12, 2018

Science Daily/IOS Press

The rate of decline in certain aspects of memory may be explained by a combination of overall physical fitness and the stiffness of the central arteries.

A study to be published in the Journal of Alzheimer's Disease considers the mechanisms underlying cognitive performance in older people living independently. Lead author, PhD candidate Greg Kennedy, says that from early adulthood, memory and other aspects of cognition slowly decline, with an increasing risk of developing into dementia in later life.

"Exactly why this occurs is unclear, but research indicates that exercise and physical fitness are protective," Mr Kennedy says. "A healthier, more elastic aorta is also theorised to protect cognitive function, by reducing the negative effects of excessive blood pressure on the brain."

The study investigated whether fitness was associated with better cognition through a healthier aorta. Physical fitness and arterial stiffness assessment One hundred and two people (73 females and 29 males), aged between 60 and 90 years, living independently in aged care communities, were recruited in Melbourne, Australia.

Their fitness was assessed with the Six-Minute Walk test which involved participants walking back and forth between two markers placed 10 metres apart for six minutes.

Only participants who completed the full six minutes were included in the analysis, which assessed the stiffness of their arteries and cognitive performance.

"People generally are less fit and have stiffer arteries as they age, which seems to explain the difference in memory ability that is usually attributed to 'getting older'," Mr Kennedy says.

Interestingly, physical fitness did not seem to affect central arterial stiffness, however Mr Kennedy points out that only current fitness was assessed -- long term fitness may be a better predictor of central arterial stiffness, however this has yet to be investigated.

"Unfortunately, there is currently no effective pharmacological intervention that has proven effective in the long term in reducing this decline or staving off dementia," Mr Kennedy says.

"The results of this study indicate that remaining as physically fit as possible, and monitoring central arterial health, may well be an important, cost effective way to maintain our memory and other brain functions in older age."

https://www.sciencedaily.com/releases/2018/06/180612092122.htm

Waves move across the human brain to support memory

Columbia Engineers discover a new fundamental feature of brain oscillations: These traveling waves reflect patterns of neuronal activity that move across the cortex and are important for memory and cognition

June 7, 2018

Science Daily/Columbia University School of Engineering and Applied Science

Engineers have discovered a new fundamental feature of brain oscillations: they actually move rhythmically across the brain, reflecting patterns of neuronal activity that propagate across the cortex. The researchers also found that the traveling waves moved more reliably when subjects performed well while performing a working memory task, indicating traveling waves are important for memory and cognition: the waves play a significant role in supporting brain connectivity.

The coordination of neural activity across widespread brain networks is essential for human cognition. Researchers have long assumed that oscillations in the brain, commonly measured for research purposes, brain-computer interfacing, and clinical tests, were stationary signals that occurred independently at separate brain regions. Biomedical engineers at Columbia Engineering have discovered a new fundamental feature of brain oscillations: they actually move rhythmically across the brain, reflecting patterns of neuronal activity that propagate across the cortex. The study was published today in Neuron.

"We also found that these traveling waves moved more reliably when subjects performed well while performing a working memory task," says Joshua Jacobs, assistant professor of biomedical engineering and senior author of the paper. "This indicates that traveling waves are significant for memory and cognition -- our findings show that these oscillations are an important mechanism for large-scale coordination in the human brain."

Jacobs' team studied direct brain recordings from 77 epilepsy patients, who had had electrodes placed in widespread brain areas for seizure mapping. For Jacobs' study, the patients were asked to perform a memory task. In examining the brain recordings from these patients, the researchers found large brain regions in individual patients with "theta" and "alpha" oscillations, which are linked to cognition, at specific frequencies between 2 to 15 Hz. These oscillations indicate that the neurons in this region rhythmically activated to support cognition, but the specific role performed by these oscillations has remained unclear.

The group used two novel methods to analyze the data. First, they measured individual oscillations simultaneously from multiple electrodes instead of using the more common method of measuring each brain wave separately from individual locations. Second, they developed a new analytical framework that enabled them to measure the instantaneous movement of each traveling wave. Using this approach, they found that the oscillations were actually traveling waves that moved across the cortex at 0.25-0.75 m/s.

"The traveling waves were relevant behaviorally because their propagation correlated with task events and was more consistent when subjects performed the task well," says Honghui Zhang, a postdoc in Jacobs' lab and the paper's lead author.

The study's findings demonstrate that the brain uses neuronal oscillations to propagate information across different regions, and that, by organizing neural processes across space and time, traveling waves play a significant role in supporting brain connectivity.

"Our research indicates that, when a researcher records a brain oscillation, neural activity is being communicated across the brain," says Jacobs. "So, in addition to opening new directions for fundamental brain research on connectivity and memory, our work suggests that clinicians can measure patterns of traveling waves to characterize an individual's brain connectivity. Traveling waves are like ocean waves, moving across the surface of the cortex, and may also provide a new type of signal that can be used for brain-computer interfaces."

"This recent work from the Jacobs lab is incredibly exciting," says Kareem Zaghloul, an investigator at the National Institutes of Health's Functional and Restorative Neurosurgery Unit. "The study of traveling waves opens up new directions for brain research, as it now allows us to consider not only what the brain is representing but how information moves around the brain "

Jacobs is currently exploring how traveling waves are relevant for other behaviors, including spatial navigation and long-term memory. His group is also developing new methodologies to test whether other types of brain oscillations, such as those at faster frequencies, also behave as traveling waves.

https://www.sciencedaily.com/releases/2018/06/180607135206.htm

Lighting intervention improves sleep and mood for Alzheimer's patients

Daytime light exposure decreases sleep disturbances, depression and agitation

June 5, 2018

Science Daily/American Academy of Sleep Medicine

A tailored lighting intervention in nursing homes can positively impact sleep, mood and behavior for patients with Alzheimer's disease, according to preliminary findings from a new study.

People with Alzheimer's disease and related dementias may experience sleep problems, wandering, and associated daytime irritability. This study tested whether a tailored daytime lighting intervention could improve sleep and behavior in Alzheimer's patients living in long-term care facilities.

Compared to baseline and to the inactive lighting condition, the lighting intervention significantly decreased sleep disturbances, depression and agitation. While all measures improved, the most significant improvement was seen in sleep quality.

"Here we show that if the stimulus (light dose) is carefully delivered and measured, it can have a strong impact on sleep, depression and agitation," said principal investigator and lead author Mariana Figueiro, PhD, a professor and director at the Lighting Research Center at Rensselaer Polytechnic Institute in Troy, New York. "Depression was a secondary measure, and I was pleasantly surprised by the positive impact of the light treatment on depression scores."

The study involved 43 subjects diagnosed with Alzheimer's disease and related dementias who were exposed to an active and inactive tailored lighting intervention for successive 4-week periods, spaced by a 4-week washout period. The lighting intervention was added to spaces in which patients spent most of their waking hours and was energized from wake time until 6 p.m. Calibrated personal light meters monitored exposures. Measures of sleep disturbances (Pittsburgh Sleep Quality Index), mood (Cornell Scale for Depression in Dementia) and agitation (Cohen-Mansfield Agitation Index) were collected at baseline and during the last week of the intervention.

https://www.sciencedaily.com/releases/2018/06/180605083043.htm

Insomnia is a likely long-term side effect of stroke

May 30, 2018

Science Daily/University of Surrey

Stroke patients experience sustained problems with insomnia potentially reducing their ability to relearn key skills and putting them at increased risk of depression, a new study finds.

In the first study of its kind, researchers from the University of Surrey, University of Freiburg, Germany, and the University of Bern, Switzerland, conducted an in depth sleep laboratory experiment to compare the brain signals of patients in the chronic state (at least one year post-stroke) and the general population.

Difficulties with sleeping in those who had a stroke have long been reported but little is known about the brain signals underlying poor sleep, in particular when patients are back in the community. It is also unclear how sleeping poorly during the night relates to sleepiness and fatigue during the day.

Using a polysomnogram (PSG) test, which assesses the brains' sleeping patterns over two nights, researchers found that it took stroke patients longer to fall asleep and that they had poorer sleep efficiency -- the ratio of time spent asleep comparted to the time spent in bed -- than those who had not experienced a stroke.

A multiple sleep latency test (MSLT), also showed that stroke patients were less likely to nap or fall asleep during the day to compensate for lost sleep at night. They were, however, more prone to errors in a vigilance test than their counterparts, increasing their risk of cognitive failures or falls.

Importantly researchers found that although sleep efficiency was reduced in patients, total sleep time between the groups was similar, suggesting that lesions in the brains' centres for sleep-wake regulation are unlikely to cause the insomnia. Rather researchers believe that sleep problems experienced by stroke patients are due to a number of contributory factors, such as greater psychological strain, pain and discomfort as well as reduced levels of physical activity.

Annette Sterr, Professor of Cognitive Neuroscience and Neuropsychology at the University of Surrey, said:

"Our research shows that those who have suffered from stroke maintain difficulties with their sleep which is likely to affect the overall recovery and quality of life. The importance of sleep in aiding the recovery of patients should not be underestimated in helping to improve and maintain physical and mental wellbeing.

"Presently sleep is not considered in the NICE guidelines for stroke rehabilitation, an issue we hope will be revisited by the organisation in due course. Harnessing the power of good sleep is likely to maximise recovery and quality of life."

https://www.sciencedaily.com/releases/2018/05/180530113136.htm

Study of 'SuperAgers' offers genetic clues to performance

MAP2K3 genetic variants could help slow age-related memory loss

May 30, 2018

Science Daily/The Translational Genomics Research Institute

Recent studies have shown that SuperAgers have less evidence of brain atrophy, have thicker parts of the brain related to memory, and lower prevalence of the pathological changes associated with Alzheimer's disease. Now, a study suggests that having resilient memory performance during aging could be inherited, and that a particular gene might be associated with SuperAgers.

All humans experience some cognitive decline as they age. But how is it that some people in their 80s and beyond still have memory capacity of those 30 or more years younger?

Recent studies have shown that these SuperAgers have less evidence of brain atrophy, have thicker parts of the brain related to memory, and lower prevalence of the pathological changes associated with Alzheimer's disease.

Now, a study by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and Northwestern University Feinberg School of Medicine suggests that having resilient memory performance during aging could be inherited, and that a particular gene might be associated with SuperAgers.

The study results, published today in the journal Frontiers in Aging Neuroscience, suggest that therapies targeting the MAP2K3 gene could reduce age-related memory decline, and perhaps the threat of memory loss posed by Alzheimer's disease.

"This study suggests that SuperAgers may have a genetic 'leg up' on the normal aging population -- they may have higher resistance to age-related cognitive changes -- and also that this might highlight a new way to enhance memory performance," said Dr. Matt Huentelman, Ph.D., TGen Professor of Neurogenomics, and the study's lead author.

Researchers sequenced the genomes of 56 SuperAgers in the hunt for genetic variations. They defined SuperAgers as those individuals 80 years or older who scored at or above average normative values for adults age 50-65 in episodic memory tests, and at least average-for-age in other cognitive tests.

They compared these to a control group of 22 cognitively average individuals, those who scored within the average-for-age on episodic memory and other cognitive tests, as well as with a large group of individuals from the general population.

They found that the SuperAgers were enriched for genetic changes in the MAP2K3 gene compared to the two control groups.

"Based on our findings, we postulate MAP2K3 inhibitors may represent a novel therapeutic strategy for enhanced cognition and resistance to Alzheimer's disease," said Dr. Emily J. Rogalski, Ph.D., Associate Professor at the Mesulam Cognitive Neurology and Alzheimer's Disease Center at Northwestern's Feinberg School of Medicine, and the study's senior author. "Replication of the finding and mechanistic studies are important next steps."

https://www.sciencedaily.com/releases/2018/05/180530113217.htm

Depression speeds up brain aging, find psychologists

Psychologists have found a link between depression and an acceleration of the rate at which the brain ages

May 24, 2018

Science Daily/University of Sussex

Psychologists at the University of Sussex have found a link between depression and an acceleration of the rate at which the brain ages. Although scientists have previously reported that people with depression or anxiety have an increased risk of dementia in later life, this is the first study that provides comprehensive evidence for the effect of depression on decline in overall cognitive function (also referred to as cognitive state), in a general population.

For the study, published today, Thursday 24 May 2018, in the journal Psychological Medicine, researchers conducted a robust systematic review of 34 longitudinal studies, with the focus on the link between depression or anxiety and decline in cognitive function over time. Evidence from more than 71,000 participants was combined and reviewed. Including people who presented with symptoms of depression as well as those that were diagnosed as clinically depressed, the study looked at the rate of decline of overall cognitive state -- encompassing memory loss, executive function (such as decision making) and information processing speed -- in older adults.

Importantly, any studies of participants who were diagnosed with dementia at the start of study were excluded from the analysis. This was done in order to assess more broadly the impact of depression on cognitive ageing in the general population. The study found that people with depression experienced a greater decline in cognitive state in older adulthood than those without depression. As there is a long pre-clinical period of several decades before dementia may be diagnosed, the findings are important for early interventions as currently there is no cure for the disease.

Lead authors of the paper, Dr Darya Gaysina and Amber John from the EDGE (Environment, Development, Genetics and Epigenetics in Psychology and Psychiatry) Lab at the University of Sussex, are calling for greater awareness of the importance of supporting mental health to protect brain health in later life.

Dr Gaysina, a Lecturer in Psychology and EDGE Lab Lead, comments: "This study is of great importance -- our populations are ageing at a rapid rate and the number of people living with decreasing cognitive abilities and dementia is expected to grow substantially over the next thirty years.

"Our findings should give the government even more reason to take mental health issues seriously and to ensure that health provisions are properly resourced. We need to protect the mental wellbeing of our older adults and to provide robust support services to those experiencing depression and anxiety in order to safeguard brain function in later life."

Researcher Amber John, who carried out this research for her PhD at the University of Sussex adds: "Depression is a common mental health problem -- each year, at least 1 in 5 people in the UK experience symptoms. But people living with depression shouldn't despair -- it's not inevitable that you will see a greater decline in cognitive abilities and taking preventative measures such as exercising, practicing mindfulness and undertaking recommended therapeutic treatments, such as Cognitive Behaviour Therapy, have all been shown to be helpful in supporting wellbeing, which in turn may help to protect cognitive health in older age."

https://www.sciencedaily.com/releases/2018/05/180524081735.htm

Moderate to high intensity exercise does not slow cognitive decline in people with dementia

May 16, 2018

Science Daily/BMJ

Moderate to high intensity exercise does not slow cognitive (mental) impairment in older people with dementia, finds a new trial.

Although the exercise programme improved physical fitness, it cannot be recommended as a treatment option for cognitive impairment in dementia, say the researchers.

Nearly 47.5 million people worldwide have dementia and the view that exercise might slow cognitive decline has gained widespread popularity. But recent reviews of trials of exercise training in people with dementia have shown conflicting results.

To try and resolve this uncertainty, a team of UK researchers decided to estimate the effect of a moderate to high intensity aerobic and strength exercise training programme on cognitive impairment and other outcomes in people with dementia.

The trial involved 494 people with mild to moderate dementia (average age 77 years) living in the community across 15 regions of England.

General health and fitness was assessed at the start of the study and participants were randomly assigned to either a supervised exercise and support programme (329 patients) or to usual care (165 patients).

The programme consisted of 60-90 minute group sessions in a gym twice a week for four months, plus home exercises for one additional hour each week with ongoing support.

The main (primary) outcome was an Alzheimer's disease assessment score (ADAS-cog) at 12 months. Other (secondary) outcomes included activities of daily living, number of falls, and quality of life.

Compliance with exercise was good and participants were assessed again at six and 12 months.

After taking account of potentially influential factors, the researchers found that cognitive impairment declined over the 12-month follow-up in both groups.

The exercise group showed improved physical fitness in the short term, but higher ADAS-cog scores at 12 months (25.2 v 23.8) compared with the usual care group, indicating worse cognitive impairment. However, the average difference was small and clinical relevance was uncertain.

No differences were found in secondary outcomes, including number of falls and quality of life, or after further analyses to test the strength of the results.

The researchers point to some trial limitations. For example, participants and carers knew which group they were in, and the period of structured exercise may have been too short to produce positive benefits. However, strengths over previous trials included a substantially larger sample size and high levels of follow-up.

"This trial suggests that people with mild to moderate dementia can engage and comply with moderate to high intensity aerobic and strengthening exercise and improve physical fitness," say the authors.

"These benefits do not, however, translate into improvements in cognitive impairment, activities in daily living, behaviour, or health related quality of life," they add.

They suggest that future trials should explore other forms of exercise, and that investigators "should consider the possibility that some types of exercise intervention might worsen cognitive impairment."

https://www.sciencedaily.com/releases/2018/05/180516184930.htm

For older adults, a better diet may prevent brain shrinkage

May 16, 2018

Science Daily/American Academy of Neurology

People who eat a diet rich in vegetables, fruit, nuts and fish may have bigger brains, according to a new study.

"People with greater brain volume have been shown in other studies to have better cognitive abilities, so initiatives that help improve diet quality may be a good strategy to maintain thinking skills in older adults," said study author Meike W. Vernooij, MD, PhD, of the Erasmus University Medical Center in Rotterdam, the Netherlands. "More research is needed to confirm these results and to examine the pathways through which diet can affect the brain."

The study included 4,213 people in the Netherlands with an average age of 66 who did not have dementia.

Participants completed a questionnaire asking how much they ate of nearly 400 items over the past month. Researchers looked at diet quality based on the Dutch dietary guidelines by examining intake of foods in the following groups: vegetables, fruit, whole grain products, legumes, nuts, dairy, fish, tea, unsaturated fats and oils of total fats, red and processed meat, sugary beverages, alcohol and salt. Researchers ranked the quality of diet for each person with a score of zero to 14. The best diet consisted of vegetables, fruit, nuts, whole grains, dairy and fish, but a limited intake of sugary drinks. The average score of participants was seven.

All participants had brain scans with magnetic resonance imaging to determine brain volume, the number of brain white matter lesions and small brain bleeds. The participants had an average total brain volume of 932 milliliters.

Information was also gathered on other factors that could affect brain volumes, such as high blood pressure, smoking and physical activity.

Researchers found after adjusting for age, sex, education, smoking and physical activity that a higher diet score was linked to larger total brain volume, when taking into account head size differences. Those who consumed a better diet had an average of two milliliters more total brain volume than those who did not. To compare, having a brain volume that is 3.6 milliliters smaller is equivalent to one year of aging.

Diet was not linked to brain white matter lesions or small brain bleeds.

For comparison, researchers also assessed diet based on the Mediterranean diet, which is also rich in vegetables, fish and nuts, and found brain volume results were similar to those who adhered closely to Dutch dietary guidelines.

Vernooij said the link between better overall diet quality and larger total brain volume was not driven by one specific food group, but rather several food groups.

"There are many complex interactions that can occur across different food components and nutrients and according to our research, people who ate a combination of healthier foods had larger brain tissue volumes," Vernooij said.

She noted that because the study was a snapshot in time, it does not prove that a better diet results in a larger brain volume; it only shows an association.

Limitations of the study include that diet was self-reported and relied on someone's ability to remember what they ate over one month, and the study was conducted in a Dutch population and therefore other populations may not have similar results.

https://www.sciencedaily.com/releases/2018/05/180516162539.htm

Move it and use it: Exergaming may help those at risk of Alzheimer's or related dementias

May 15, 2018

Science Daily/Union College

Older adults with mild cognitive impairment (MCI), often a precursor to Alzheimer's, showed significant improvement with certain complex thinking and memory skills after exergaming, according to a new study. The results could encourage seniors, caregivers and health care providers to pursue or prescribe exergames (video games that also require physical exercise) in hopes of slowing the debilitating effects of those with MCI, sometimes a stage between normal brain aging and dementia.

The results could encourage seniors, caregivers and health care providers to pursue or prescribe exergames (video games that also require physical exercise) in hopes of slowing the debilitating effects of those with MCI, sometimes a stage between normal brain aging and dementia.

"It's promising data," said Cay Anderson-Hanley, associate professor of psychology at Union College and the study's lead author. "Exergaming is one more thing that could be added to the arsenal of tools to fight back against this cruel disease."

The study appears in the current issue of Frontiers in Aging Neuroscience.

Previously published research by Anderson-Hanley and others found that seniors who exercise using the features of interactive video games experienced greater cognitive health benefits than those who rely on traditional exercise alone.

For the latest study, researchers wanted to target older adults diagnosed with or at risk for MCI. MCI is most common in people over age 55. By age 65, approximately 15 to 20 percent of the population shows signs of MCI, according to the Alzheimer's Association.

Researchers initially enrolled more than 100 seniors for the study, which was funded through a grant from the National Institute on Aging. Over six months, 14 (evenly split between men and women) persisted with regular exergaming. The average age was 78.

The first group of seven was assigned to pedal along a scenic virtual reality bike path several times a week. The second group was given a more challenging task for the brain: pedal while playing a video game that included chasing dragons and collecting coins.

The special bikes were placed at a number of sites, including hospitals, community centers and independent living centers.

The results were compared against data collected from a separate group of eight seniors who played video games on a laptop but did not pedal, and also a group from the previous research who only rode a traditional stationary bike with no gaming component.

At the end of the randomized clinical trial, participants in both the group that pedaled along a virtual bike path and those that chased dragons and collected coins experienced significantly better executive function, which controls, in part, multi-tasking and decision making.

"Executive function is like the CEO of the brain. It is key to remaining independent in later life," said Anderson-Hanley. "For example, it allows you to cook two things on the stove at once. It makes sure you don't forget that you are boiling water while also having something in the oven."

Benefits for both groups were also seen for verbal memory and physical function, suggesting it may be worth the effort for seniors to incorporate exergaming into a daily exercise regime.

Anderson-Hanley acknowledged that further research with a larger sample size is needed to confirm the team's findings. One of the challenges faced was getting older adults in the habit of going to the gym or another venue to exergame. The team is working on a way to have seniors stay home and upload a video game to an iPad that can be used with a stationary bike.

In the meantime, the research suggests benefits of exercising while also stimulating the brain with some mental challenge, such as navigating a scenic bike path or interactively playing a video game.

"The goal is to explore even more effective ways to prevent or ameliorate cognitive decline in older adults by tailoring accessibility and level of mental engagement in interactive cognitive and physical exercise," she said. "The results suggest that the best outcome for brain health may result when we do both: move it and use it."

https://www.sciencedaily.com/releases/2018/05/180515081728.htm

The Yogi masters were right -- meditation and breathing exercises can sharpen your mind

New research explains link between breath-focused meditation and attention and brain health

May 10, 2018

Science Daily/Trinity College Dublin

It has long been claimed by Yogis and Buddhists that meditation and ancient breath-focused practices, such as pranayama, strengthen our ability to focus on tasks. A new study explains for the first time the neurophysiological link between breathing and attention.

Breath-focused meditation and yogic breathing practices have numerous known cognitive benefits, including increased ability to focus, decreased mind wandering, improved arousal levels, more positive emotions, decreased emotional reactivity, along with many others. To date, however, no direct neurophysiological link between respiration and cognition has been suggested.

The research shows for the first time that breathing -- a key element of meditation and mindfulness practices -- directly affects the levels of a natural chemical messenger in the brain called noradrenaline. This chemical messenger is released when we are challenged, curious, exercised, focused or emotionally aroused, and, if produced at the right levels, helps the brain grow new connections, like a brain fertiliser. The way we breathe, in other words, directly affects the chemistry of our brains in a way that can enhance our attention and improve our brain health.

The study, carried out by researchers at Trinity College Institute of Neuroscience and the Global Brain Health Institute at Trinity, found that participants who focused well while undertaking a task that demanded a lot of attention had greater synchronisation between their breathing patterns and their attention, than those who had poor focus. The authors believe that it may be possible to use breath-control practices to stabilise attention and boost brain health.

Michael Melnychuk, PhD candidate at the Trinity College Institute of Neuroscience, Trinity, and lead author of the study, explained: "Practitioners of yoga have claimed for some 2,500 years, that respiration influences the mind. In our study we looked for a neurophysiological link that could help explain these claims by measuring breathing, reaction time, and brain activity in a small area in the brainstem called the locus coeruleus, where noradrenaline is made. Noradrenaline is an all-purpose action system in the brain. When we are stressed we produce too much noradrenaline and we can't focus. When we feel sluggish, we produce too little and again, we can't focus. There is a sweet spot of noradrenaline in which our emotions, thinking and memory are much clearer."

"This study has shown that as you breathe in locus coeruleus activity is increasing slightly, and as you breathe out it decreases. Put simply this means that our attention is influenced by our breath and that it rises and falls with the cycle of respiration. It is possible that by focusing on and regulating your breathing you can optimise your attention level and likewise, by focusing on your attention level, your breathing becomes more synchronised."

The research provides deeper scientific understanding of the neurophysiological mechanisms which underlie ancient meditation practices. The findings were recently published in a paper entitled 'Coupling of respiration and attention via the locus coeruleus: Effects of meditation and pranayama' in the journal Psychophysiology. Further research could help with the development of non-pharmacological therapies for people with attention compromised conditions such as ADHD and traumatic brain injury and in supporting cognition in older people.

There are traditionally two types of breath-focused practices -- those that emphasise focus on breathing (mindfulness), and those that require breathing to be controlled (deep breathing practices such as pranayama). In cases when a person's attention is compromised, practices which emphasise concentration and focus, such as mindfulness, where the individual focuses on feeling the sensations of respiration but make no effort to control them, could possibly be most beneficial. In cases where a person's level of arousal is the cause of poor attention, for example drowsiness while driving, a pounding heart during an exam, or during a panic attack, it should be possible to alter the level of arousal in the body by controlling breathing. Both of these techniques have been shown to be effective in both the short and the long term.

Ian Robertson, Co-Director of the Global Brain Health Institute at Trinity and Principal Investigator of the study added: "Yogis and Buddhist practitioners have long considered the breath an especially suitable object for meditation. It is believed that by observing the breath, and regulating it in precise ways -- a practice known as pranayama -- changes in arousal, attention, and emotional control that can be of great benefit to the meditator are realised. Our research finds that there is evidence to support the view that there is a strong connection between breath-centred practices and a steadiness of mind."

"Our findings could have particular implications for research into brain ageing. Brains typically lose mass as they age, but less so in the brains of long term meditators. More 'youthful' brains have a reduced risk of dementia and mindfulness meditation techniques actually strengthen brain networks. Our research offers one possible reason for this -- using our breath to control one of the brain's natural chemical messengers, noradrenaline, which in the right 'dose' helps the brain grow new connections between cells. This study provides one more reason for everyone to boost the health of their brain using a whole range of activities ranging from aerobic exercise to mindfulness meditation."

https://www.sciencedaily.com/releases/2018/05/180510101254.htm

Depression linked to memory problems and brain aging

May 9, 2018

Science Daily/American Academy of Neurology

Depression in older adults may be linked to memory problems, according to new research. The study also showed that older people with greater symptoms of depression may have structural differences in the brain compared to people without symptoms.

"Since symptoms of depression can be treated, it may be possible that treatment may also reduce thinking and memory problems," said study author Adina Zeki Al Hazzouri, PhD, MS, of the University of Miami Miller School of Medicine in Florida. "With as many as 25 percent of older adults experiencing symptoms of depression, it's important to better understand the relationship between depression and memory problems."

The study involved 1,111 people who were all stroke-free with an average age of 71. The majority were Caribbean Hispanic. At the beginning of the study, all had brain scans, a psychological exam and assessments for memory and thinking skills. Their memory and thinking skills were tested again an average of five years later.

At the start of the study, 22 percent of participants had greater symptoms of depression. This was defined as a score of 16 or higher on a test with a range of 0-60, which is considered at risk for clinical depression. For the test, participants reported how often in the past week they agreed with statements such as "I was bothered by things that usually don't bother me" and "I did not feel like eating." Researchers found after adjusting for age, race, anti-depressive medications, and other variables, greater symptoms of depression were linked to worse episodic memory. Scores on tests were lower by 0.21 of a standard deviation compared to those without greater symptoms of depression. Episodic memory is a person's ability to remember specific experiences and events.

Researchers also found those with greater symptoms of depression had differences in the brain including smaller brain volume as well as a 55 percent greater chance of small vascular lesions in the brain.

Researchers found no evidence of a relationship between greater symptoms of depression and changes in thinking skills over five years.

"Small vascular lesions in the brain are markers of small vessel disease, a condition in which the walls in the small blood vessels are damaged," said Zeki Al Hazzouri. "Our research suggests that depression and brain aging may occur simultaneously, and greater symptoms of depression may affect brain health through small vessel disease."

Zeki Al Hazzouri noted that the study provides information about depression and memory and thinking skills, especially among people who identified as Hispanic, who have been insufficiently studied in previous studies on the topic, even though they can be at increased risk of dementia in late life.

Limitations of the study include that participants had to be healthy enough to have an MRI, so they may have been healthier than the general population. Also, the study was over a five-year period, which may not have been long enough to capture meaningful changes in thinking and memory abilities over time.

https://www.sciencedaily.com/releases/2018/05/180509162704.htm

Researchers discover connection between circadian rhythm and aggression

May 2, 2018

Science Daily/University of Copenhagen The Faculty of Health and Medical Sciences

A research team has discovered a circuit in the brains of mice connecting circadian rhythm to aggressive behavior. The discovery is particularly interesting to Alzheimer's patients who experience increased aggression at night. The researchers have developed special protein tools capable of turning off the cells in the brain causing the behavior.

Each year around many people worldwide are diagnosed with a form of dementia. Alzheimer's disease is one of them. The disease manifests itself in memory difficulties in particular, but can also result in personality changes and mood swings.

When the sun sets 20 per cent of all Alzheimer's patients experience increased bewilderment, anxiety, unease, disorientation, irritation and aggression. This phenomenon is called 'sundowning' or sundown syndrome. At worst, the condition can mean that the patient must be left in professional care, as it can be difficult for family members to handle. The cause of the condition is unknown, but previous research has suggested that it is connected to the circadian rhythm.

A research team including a researcher from the Department of Drug Design and Pharmacology at the University of Copenhagen is now able to confirm this connection. The researchers have identified and mapped a circuit between the part of the brain containing the circadian clock or circadian rhythm and a part of the brain controlling aggression.

'We have shown that the circadian clock in mice is closely linked to an aggression centre in the mouse brain by a cell circuit. The human brain has those same groups of cells that the circuit goes through. With this knowledge, we are now enabled to target this circuit pharmacologically and target cells that make people aggressive at the end of the day', says Assistant Professor Timothy Lynagh from the Department of Drug Design and Pharmacology at the University of Copenhagen.

Turn off the Aggression

The inner clock or circadian rhythm is located in the part of the brain called suprachiasmatic nucleus. One of the parts of the brain that control aggressive behaviour is called the ventromedial hypothalamus. Researchers have previously observed a connection between the two parts of the brain, though none have had knowledge of the specific circuit connecting them.

Using electrophysiology and microscopy, the researchers measured the activity of the brain cells at main author Clifford Saper's laboratory in Boston. They also turned off parts of the cell circuit in the brains of mice to map the circuit and to identify the cells connecting the two parts of the brain. To map circuits in the brain you need a protein tool that can turn off the various cells to determine their function. Assistant Professor Timothy Lynagh has designed precisely such a tool.

'We take a receptor and mutate it, so that it is not sensitive to anything in the brain, but very sensitive to a particular drug. The tool works like an on/off switch. When you put the protein tool in the mouse brain, under normal circumstances, nothing will happen. But when you give the animal the drug, the cells that have the receptor on them will be turned off', Timothy Lynagh explains.

Using this tool, the researchers can thus in theory turn off the cells that cause people suffering from sundown syndrome to become more aggressive at night.

May Be Used on Humans 20 Years into the Future

The tool can also be used in other contexts than sundown syndrome. In other studies, Tim Lynagh's tool has been used to turn off cells in rats linked to anxiety and fear.

'If you can start understanding which cells in the brain lead to which problems, you can then put this tool into any of those parts of the brain. The person who takes the drug will then have the cells causing the problem turned off', Timothy Lynagh says.

Even though the study was conducted on mice, the tool and the knowledge the research has generated can potentially be used in the treatment of humans.

'Because of the huge advances that are coming along with CRISPR, I would be tempted to say that based on a recent demonstration of gene therapy for brain disease, potentially, it could be used in the human brain in 20 years' time. Of course it needs a lot more research', he says.

https://www.sciencedaily.com/releases/2018/05/180502104100.htm

Music activates regions of the brain spared by Alzheimer's disease

April 28, 2018

Science Daily/University of Utah Health

Researchers are looking to the salience network of the brain to develop music-based treatments to help alleviate anxiety in patients with dementia.

Ever get chills listening to a particularly moving piece of music? You can thank the salience network of the brain for that emotional joint. Surprisingly, this region also remains an island of remembrance that is spared from the ravages of Alzheimer's disease. Researchers at the University of Utah Health are looking to this region of the brain to develop music-based treatments to help alleviate anxiety in patients with dementia. Their research will appear in the April online issue of The Journal of Prevention of Alzheimer's Disease.

"People with dementia are confronted by a world that is unfamiliar to them, which causes disorientation and anxiety" said Jeff Anderson, M.D., Ph.D., associate professor in Radiology at U of U Health and contributing author on the study. "We believe music will tap into the salience network of the brain that is still relatively functioning."

Previous work demonstrated the effect of a personalized music program on mood for dementia patients. This study set out to examine a mechanism that activates the attentional network in the salience region of the brain. The results offer a new way to approach anxiety, depression and agitation in patients with dementia. Activation of neighboring regions of the brain may also offer opportunities to delay the continued decline caused by the disease.

For three weeks, the researchers helped participants select meaningful songs and trained the patient and caregiver on how to use a portable media player loaded with the self-selected collection of music.

"When you put headphones on dementia patients and play familiar music, they come alive," said Jace King, a graduate student in the Brain Network Lab and first author on the paper. "Music is like an anchor, grounding the patient back in reality."

Using a functional MRI, the researchers scanned the patients to image the regions of the brain that lit up when they listened to 20-second clips of music versus silence. The researchers played eight clips of music from the patient's music collection, eight clips of the same music played in reverse and eight blocks of silence. The researchers compared the images from each scan.

The researchers found that music activates the brain, causing whole regions to communicate. By listening to the personal soundtrack, the visual network, the salience network, the executive network and the cerebellar and corticocerebellar network pairs all showed significantly higher functional connectivity.

"This is objective evidence from brain imaging that shows personally meaningful music is an alternative route for communicating with patients who have Alzheimer's disease," said Norman Foster, M.D., Director of the Center for Alzheimer's Care at U of U Health and senior author on the paper. "Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment."

However, these results are by no means conclusive. The researchers note the small sample size (17 participants) for this study. In addition, the study only included a single imaging session for each patient. It is remains unclear whether the effects identified in this study persist beyond a brief period of stimulation or whether other areas of memory or mood are enhanced by changes in neural activation and connectivity for the long term.

"In our society, the diagnoses of dementia are snowballing and are taxing resources to the max," Anderson said. "No one says playing music will be a cure for Alzheimer's disease, but it might make the symptoms more manageable, decrease the cost of care and improve a patient's quality of life."

https://www.sciencedaily.com/releases/2018/04/180428145111.htm

Vitamin B6 helps people recall their dreams

April 27, 2018

Science Daily/University of Adelaide

New research has found that taking vitamin B6 could help people to recall their dreams.

The study published online ahead of print in Perceptual and Motor Skills, included 100 participants from around Australia taking high-dose vitamin B6 supplements before going to bed for five consecutive days.

"Our results show that taking vitamin B6 improved people's ability to recall dreams compared to a placebo," says research author Dr Denholm Aspy, from the University's School of Psychology.

"Vitamin B6 did not affect the vividness, bizarreness or colour of their dreams, and did not affect other aspects of their sleep patterns.

"This is the first time that such a study into the effects of vitamin B6 and other B vitamins on dreams has been carried out on a large and diverse group of people," Dr Aspy says.

The randomised, double-blind, placebo-controlled study saw participants taking 240mg of vitamin B6 immediately before bed.

Prior to taking the supplements, many of the participants rarely remembered their dreams, but they reported improvements by the end of the study.

"It seems as time went on my dreams were clearer and clearer and easier to remember. I also did not lose fragments as the day went on," said one of the participants after completing the study.

According to another participant of the study, "My dreams were more real, I couldn't wait to go to bed and dream!"

Dr Aspy says: "The average person spends around six years of their lives dreaming. If we are able to become lucid and control our dreams, we can then use our dreaming time more productively.

"Lucid dreaming, where you know that you are dreaming while the dream is still happening, has many potential benefits. For example, it may be possible to use lucid dreaming for overcoming nightmares, treating phobias, creative problem solving, refining motor skills and even helping with rehabilitation from physical trauma.

"In order to have lucid dreams it is very important to first be able to recall dreams on a regular basis. This study suggests that vitamin B6 may be one way to help people have lucid dreams."

Vitamin B6 occurs naturally in various foods, including whole grain cereals, legumes, fruits (such as banana and avocado), vegetables (such as spinach and potato), milk, cheese, eggs, red meat, liver, and fish.

"Further research is needed to investigate whether the effects of vitamin B6 vary according to how much is obtained from the diet. If vitamin B6 is only effective for people with low dietary intake, its effects on dreaming may diminish with prolonged supplementation," says Dr Aspy.

https://www.sciencedaily.com/releases/2018/04/180427100258.htm

Loss of brain synchrony may explain working memory limits

April 26, 2018

Science Daily/City University London

A new study may have revealed the reasons behind our memory limitations. The researchers found that trying to retain too much information in our working memory leads to a communication breakdown between parts of the brain responsible for maintaining it.

Everyday experience makes it obvious -- sometimes frustratingly so -- that our working memory capacity is limited and we can only keep so many things consciously in mind at once. The results of a new study, which is published in the journal Cerebral Cortex, may explain why: The authors suggest that the 'coupling', or synchrony, of brain waves among three key regions breaks down in specific ways when visual working memory load becomes too much to handle. This loss of synchrony means the regions can no longer communicate with each other to sustain working memory.

Maximum working memory capacity -- for instance the total number of images a person can hold in working memory at the same time -- varies between individuals but averages about seven. This new study tries to understand what causes the memory to have this intrinsic limit.

The study's lead author, Dr Dimitris Pinotsis, a lecturer at the Department of Psychology at City, University of London, and a research affiliate at the Department of Brain and Cognitive Sciences at MIT, said: "At peak memory capacity, the brain signals that maintain memories and guide actions based on these memories, reach their maximum. Above this peak, the same signals break down."

As researchers have previously correlated working memory capacity with intelligence, understanding what causes working memory to have an intrinsic limit is important because it could also help explain the limited nature of conscious thought and how it might break down in diseases.

"Because certain psychiatric diseases can lower capacity, the findings could explain more about how such diseases interfere with thinking," said Professor Earl Miller, the study's senior author and the Picower Professor of Neuroscience at MIT's Picower Institute for Learning and Memory. The study's other author is Dr Timothy Buschman, assistant professor at the Princeton University Neuroscience Institute.

To investigate working memory limits, the researchers carried out a detailed statistical analysis of data when animal subjects played a simple game. They had to spot the difference when they were shown a set of squares on a screen and then, after a brief blank screen, a nearly identical set in which one square had changed colour. The number of squares involved, hence the working memory load of each round, varied so that sometimes the task exceeded the animals' capacity.

As the animals played, the researchers measured the frequency and timing of brain waves produced by ensembles of neurons in three regions presumed to have an important -- though as yet unknown -- relationship in producing visual working memory: the prefrontal cortex (PFC), the frontal eye fields (FEF), and the lateral intraparietal area (LIP).

Using sophisticated mathematical techniques, they found that the regions essentially work as a committee, without much hierarchy, to keep working memory going. They also found changes as working memory approached and then exceeded capacity. In particular, the researchers found that above capacity the PFC's coupling to the FEF and LIP at low frequency stopped.

As previous studies have suggested that the PFC's role might be to employ low-frequency waves to provide the feedback the keeps the working memory system in sync, the researchers suggest that when that signal breaks down, the whole enterprise may as well. This observation may also explain why memory capacity has a finite limit.

Professor Miller said: "We knew that stimulus load degrades stimulus processing in various brain areas, but we hadn't seen any distinct change that correlated with reaching capacity, but we did see this with feedback coupling. It drops off when the subjects exceeded their capacity. The PFC stops providing feedback coupling to the FEF and LIP."

The findings could also help optimise heads-up displays in cars and to develop diagnostic tests for diseases like schizophrenia and dementia, among other applications.

"Understanding brain signals at peak load can help us understand the origins of cognitive impairments. This could lead to new therapeutic approaches for people in need, like schizophrenics," said Dr Pinotsis.

The US National Institute of Mental Health and the MIT's Picower Institute Innovation Fund supported this study.

https://www.sciencedaily.com/releases/2018/04/180426110502.htm

Antidepressants and bladder medicines linked to dementia in landmark study

April 25, 2018

Science Daily/University of East Anglia

Long-term use of some anticholinergic medications are associated with an increased risk of dementia, according to a new study.

Anticholinergic antidepressants have been found to be linked with dementia, even when taken up to 20 years before a diagnosis.

The research, funded by Alzheimer's Society and published today in the BMJ, also shows a dementia risk associated with medications prescribed for bladder conditions and Parkinson's.

However several other anticholinergic medications, including anti-histamines and those used for abdominal cramps, were not found to be linked to dementia -- despite previous research suggesting that any anticholinergic might represent a risk.

Anticholinergic drugs are used to treat a variety of conditions and work by blocking a key messenger (neurotransmitter) in the body called acetylcholine.

The research team studied the medical records of 40,770 patients aged over 65 diagnosed with dementia, and compared them to the records of 283,933 people without dementia. More than 27 million prescriptions were analysed.

This is the largest and most detailed study of its kind into the long-term impact of anticholinergic use in relation to dementia.

The team drilled down to see whether there were links between different classes of anticholinergic medication and incidence of dementia diagnosis.

They found that there was a greater incidence of dementia among patients prescribed greater quantities of anticholinergic antidepressants, and anticholinergic medication for bladder conditions and Parkinson's.

The link between these medications and dementia cannot tell us that they are directly causing the condition, but this work does suggests a potential preventative approach to reduce dementia which is a priority.

The study concludes that clinicians should consider long-term anti-cholinergic effects when prescribing.

Patients with concerns should continue taking their medicines until they have consulted their doctor or pharmacist.

Lead researcher Dr George Savva from UEA's School of Health Sciences said: "More than 50 million people worldwide are affected by dementia and this number is estimated to be 132 million by 2050. Developing strategies to prevent dementia is therefore a global priority.

"We studied patients with a new dementia diagnosis and looked at what anticholinergic medication they were prescribed between four and 20 years prior to being diagnosed.

"We found that people who had been diagnosed with dementia were up to 30 per cent more likely to have been prescribed specific classes of anticholinergic medications. And the association with dementia increases with greater exposure to these types of medication.

"What we don't know for sure is whether the medication is the cause. It could be that these medications are being prescribed for very early symptoms indicating the onset of dementia.

"But because our research shows that the link goes back up to 15 or 20 years before someone is eventually diagnosed with dementia, it suggests that reverse causation, or confounding with early dementia symptoms, probably isn't the case.

"This research is really important because there are an estimated 350 million people affected globally by depression, and bladder conditions requiring treatment are estimated to affect over 13 per cent of men and 30 per cent of women in the UK and US.

"Many of the treatment options for these conditions involve medication with anticholinergic effects.

Dr Doug Brown, Chief Policy and Research Officer at Alzheimer's Society, said: "This large study confirms that some anticholinergic drugs can raise the risk of dementia -- but it should also put minds at ease as there appears to be no dementia risk with anticholinergic drugs used to treat common conditions like hayfever, travel sickness and stomach cramps.

"Current guidelines for doctors say that anticholinergic drugs should be avoided for frail older people because of their impact on memory and thinking, but doctors should consider these new findings for all over-65s as long-term use could raise the risk of dementia."

Dr Noll Campbell, a collaborator and co-author on the paper, said: "These results suggest we should prioritise safer alternatives to anticholinergic medications long before symptoms of dementia are recognised." Dr Campbell is an investigator with the Regenstrief Institute and Indiana University Center for Aging Research and is an assistant professor with Purdue University College of Pharmacy in the United States.

The study used data from Clinical Practice Research Datalink which includes anonymised diagnosis, referral and prescription records for more than 11 million patients from 674 primary care practices across the UK. The data is broadly representative of the UK population in terms of age, sex and ethnicity.

Prof Chris Fox, Professor of Clinical Psychiatry at UEA's Norwich Medical School and Consultant Psychiatrist, said: "While the associations are moderate, given the high incidence of dementia, they reflect a potentially important risk to patients.

"Doctors and patients should therefore be vigilant about using anticholinergic medications.

"They need to consider the risk of long-term cognitive effects, as well as short-term effects, associated with specific drugs when weighing up risks and benefits.

"We don't know exactly how anticholinergics might cause dementia. Further research is needed to understand possible reasons for this link. In the meantime, I strongly advise patients with any concerns to continue taking their medicines until they have consulted their doctor or pharmacist."

Dr Ian Maidment, Senior Lecturer in Clinical Pharmacy at Aston University and lead pharmacist on the study, said: "We already have strong evidence that anticholinergics cause confusion and in the short-term will potentially worsen the symptoms of dementia. Long-term data is more difficult to obtain, because clinical trials tend be short term.

"This study shows that some anticholinergics may cause long-term harm in addition to short-term harm.

"Other recent research has shown a dramatic increase in polypharmacy -- the number of older people taking five or more medicines has quadrupled over 20 years to nearly half of all older people.

"With many different medicines having at least some anticholinergic activity, one focus should be de-prescribing. Doctors, nurses and pharmacists need to work with older people and their carers to ensure that they only take medication if the benefits clearly outweigh the harms."

https://www.sciencedaily.com/releases/2018/04/180425195636.htm

Lack of sleep may be linked to risk factor for Alzheimer's disease

Preliminary study shows increased levels of beta-amyloid

April 13, 2018

Science Daily/NIH/National Institute on Alcohol Abuse and Alcoholism

Losing just one night of sleep led to an immediate increase in beta-amyloid, a protein in the brain associated with Alzheimer's disease, according to a small, new study.

While acute sleep deprivation is known to elevate brain beta-amyloid levels in mice, less is known about the impact of sleep deprivation on beta-amyloid accumulation in the human brain. The study is among the first to demonstrate that sleep may play an important role in human beta-amyloid clearance.

"This research provides new insight about the potentially harmful effects of a lack of sleep on the brain and has implications for better characterizing the pathology of Alzheimer's disease," said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, which funded the study.

Beta-amyloid is a metabolic waste product present in the fluid between brain cells. In Alzheimer's disease, beta-amyloid clumps together to form amyloid plaques, negatively impacting communication between neurons.

Led by Drs. Ehsan Shokri-Kojori and Nora D. Volkow of the NIAAA Laboratory of Neuroimaging, the study is now online in the Proceedings of the National Academy of Sciences. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH.

To understand the possible link between beta-amyloid accumulation and sleep, the researchers used positron emission tomography (PET) to scan the brains of 20 healthy subjects, ranging in age from 22 to 72, after a night of rested sleep and after sleep deprivation (being awake for about 31 hours). They found beta-amyloid increases of about 5 percent after losing a night of sleep in brain regions including the thalamus and hippocampus, regions especially vulnerable to damage in the early stages of Alzheimer's disease.

In Alzheimer's disease, beta-amyloid is estimated to increase about 43 percent in affected individuals relative to healthy older adults. It is unknown whether the increase in beta-amyloid in the study participants would subside after a night of rest.

The researchers also found that study participants with larger increases in beta-amyloid reported worse mood after sleep deprivation.

"Even though our sample was small, this study demonstrated the negative effect of sleep deprivation on beta-amyloid burden in the human brain. Future studies are needed to assess the generalizability to a larger and more diverse population," said Dr. Shokri-Kojori.

It is also important to note that the link between sleep disorders and Alzheimer's risk is considered by many scientists to be "bidirectional," since elevated beta-amyloid may also lead to sleep disturbances.

https://www.sciencedaily.com/releases/2018/04/180413155301.htm

Dementia: How circadian clock controls daily rhythms of aggression

New findings shed light on the early-evening agitation known as 'sundowning,' common in patients with dementia and Alzheimer's disease

April 9, 2018

Science Daily/Beth Israel Deaconess Medical Center

Synchronized by light and darkness, the circadian clock exerts control over wake/sleep cycles, body temperature, digestion, hormonal cycles and some behavior patterns. Now, for the first time, a team of neuroscientists has demonstrated circadian control of aggression in male mice and identified the specific neurons and circuitry regulating the daily pattern. The insight opens the door to potential opportunities for managing 'sundowning,' the evening-time agitation common in patients with degenerative neurological disorders.

Now, for the first time, a team of neuroscientists at Beth Israel Deaconess Medical Center (BIDMC) has demonstrated circadian control of aggression in male mice and identified the specific neurons and circuitry regulating the daily pattern. The insight opens the door to potential opportunities for managing the evening-time agitation common in patients with degenerative neurological disorders. The study was published today in Nature Neuroscience.

"Sundowning is often the reason that patients have to be institutionalized, and if clinicians can control this circuit to minimize aggressiveness at the end of the day, patients may be able to live at home longer," said senior author Clifford B. Saper, MD, Chair of the Department of Neurology at BIDMC. "We examined the biological clock's brain circuitry and found a connection to a population of neurons known to cause violent attacks when stimulated in male mice. We wanted to know if this represented a propensity for violence at certain times of day."

Saper and colleagues observed aggressive interactions between male mice -- resident mice defending territory against intruders introduced to residents' cages at different times throughout the day. Counting the intensity and frequency of residents' attacks on intruders revealed for the first time that aggression in male mice exhibits a daily rhythm.

"The mice were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on," Saper said. "It looks like aggressiveness builds up in mice during the lights on period, and reaches a peak around the end of the light period."

Next, the scientists used genetics-based tools to manipulate neurons known to regulate the central circadian clock. When Saper and colleagues inhibited these neurons by disabling their ability to produce a specific neurotransmitter, the mice lost the daily waxing and waning of their aggressive tendencies. These genetically manipulated mice were more aggressive overall, demonstrating a significant increase in total time attacking intruders.

Using optogenetics -- a technique that uses light to activate or deactivate targeted brain cells -- to map brain circuitry revealed two parallel pathways between the biological clock and a population of neurons in a sub-region of the hypothalamus (called the VMHvl) known to cause violent attacks when stimulated in male mice.

Taken together, the experiments showed that this circadian circuit kept aggressiveness in check in the early morning; stimulating it prevented attack, while inhibiting it promoted attack. Because stimulating the neurons in question cools off aggression, Saper suggests that controlling this circuit could potentially make animals -- and perhaps people -- less aggressive.

"Our results in mice mimic the patterns of increased aggression seen in patients during sundowning," Saper said. "This new research suggests this pathway may be compromised in neurodegenerative diseases. Examining changes to this pathway in patients could provide insight into future interventions that could greatly improve the quality of life for patients and caregivers alike."

https://www.sciencedaily.com/releases/2018/04/180409185309.htm

A heavy working memory load may sink brainwave 'synch'

April 5, 2018

Science Daily/Picower Institute at MIT

When working memory load exceeds capacity, a new study finds, feedback coupling of the prefrontal cortex with other involved regions shuts down.

Everyday experience makes it obvious -- sometimes frustratingly so -- that our working memory capacity is limited. We can only keep so many things consciously in mind at once. The results of a new study may explain why: They suggest that the "coupling," or synchrony, of brain waves among three key regions breaks down in specific ways when visual working memory load becomes too much to handle.

"When you reach capacity there is a loss of feedback coupling," said senior author Earl Miller, Picower Professor of Neuroscience at MIT's Picower Institute for Learning and Memory. That loss of synchrony means the regions can no longer communicate with each other to sustain working memory.

Maximum working memory capacity -- for instance the total number of images a person can hold in working memory at the same time -- varies by individual but averages about four, Miller said. Researchers have correlated working memory capacity with intelligence.

Understanding what causes working memory to have an intrinsic limit is therefore important because it could help explain the limited nature of conscious thought and optimal cognitive performance, Miller said.

And because certain psychiatric disorders can lower capacity, said Miller and lead author Dimitris Pinotsis, a research affiliate in Miller's lab, the findings could also explain more about how such disorders interfere with thinking.

"Studies show that peak load is lower in schizophrenics and other patients with neurological or psychiatric diseases and disorders compared to healthy people," Pinotsis said. "Thus, understanding brain signals at peak load can also help us understand the origins of cognitive impairments."

The study's other author is Timothy Buschman, assistant professor at the Princeton University Neuroscience Institute and a former member of the Miller lab.

How working memory stops working

The new study published in the journal Cerebral Cortex is a detailed statistical analysis of data the Miller lab recorded when animal subjects played a simple game: They had to spot the difference when they were shown a set of squares on a screen and then, after a brief blank screen, a nearly identical set in which one square had changed color. The number of squares involved, hence the working memory load of each round, varied so that sometimes the task exceeded the animals' capacity.

As the animals played, the researchers measured the frequency and timing of brain waves produced by ensembles of neurons in three regions presumed to have an important -- though as yet unknown -- relationship in producing visual working memory: the prefrontal cortex (PFC), the frontal eye fields (FEF), and the lateral intraparietal area (LIP).

The researchers' goal was to characterize the crosstalk among these three areas, as reflected by patterns in the brain waves, and to understand specifically how that might change as load increased to the point where it exceeded capacity.

Though the researchers focused on these three areas, they didn't know how they might work with each other. Using sophisticated mathematical techniques, they tested scores of varieties of how the regions "couple," or synchronize, at high- and low-frequencies. The "winning" structure was whichever one best fit the experimental evidence.

"It was very open ended," Miller said. "We modeled all different combinations of feedback and feedforward signals among the areas and waited to see where the data would lead."

They found that the regions essentially work as a committee, without much hierarchy, to keep working memory going. They also found changes as load approached and then exceeded capacity.

"At peak memory load, the brain signals that maintain memories and guide actions based on these memories, reach their maximum," Pinotsis said. "Above this peak, the same signals break down."

In particular, above capacity the PFC's coupling to other regions at low frequency stopped, Miller said.

Other research suggests that the PFC's role might be to employ low-frequency waves to provide the feedback the keeps the working memory system in synch. When that signal breaks down, Miller said, the whole enterprise may as well. That may explain why memory capacity has a finite limit. In prior studies, he said, his lab has observed that the information in neurons degrades as load increases, but there wasn't an obvious cut-off where working memory would just stop functioning.

"We knew that stimulus load degrades processing in these areas, but we hadn't seen any distinct change that correlated with reaching capacity," he said. "But we did see this with feedback coupling. It drops off when the subjects exceeded their capacity. The PFC stops providing feedback coupling to the FEF and LIP."

Two sides to the story

Because the study game purposely varied where the squares appeared on the left or right side of the visual field, the data also added more evidence for a discovery Miller and colleagues first reported back in 2009: Visual working memory is distinct for each side of the visual field. People have independent capacities on their left and their right, research has confirmed.

The Miller Lab is now working on a new study that tracks how the three regions interact when working memory information must be shared across the visual field.

The insights Miller's lab has produced into visual working memory led him to start the company SplitSage, which last month earned a patent for technology to measure people's positional differences in visual working memory capacity. The company hopes to use insights from Miller's research to optimize heads-up displays in cars and to develop diagnostic tests for disorders like dementia among other applications. Miller is the company's chief scientist and Buschman is chair of the advisory board.

The more scientists learn about how working memory works, and more generally about how brain waves synchronize higher level cognitive functions, the more ways they may be able to apply that knowledge to help people, Miller said.

"If we can figure out what things rhythms are doing and how they are doing them and when they are doing them, we may be able to find a way to strengthen the rhythms when they need to be strengthened," he said.

https://www.sciencedaily.com/releases/2018/04/180405093204.htm