Fundamental rule of brain plasticity
June 21, 2018
Science Daily/Picower Institute at MIT
A series of complex experiments in the visual cortex of mice has yielded a simple rule about plasticity: When a synapse strengthens, others immediately nearby weaken.
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must compensate lest they become overwhelmed with input. In a new study in Science, researchers at the Picower Institute for Learning and Memory at MIT demonstrate for the first time how this balance is struck: when one connection, called a synapse, strengthens, immediately neighboring synapses weaken based on the action of a crucial protein called Arc.
Senior author Mriganka Sur said he was excited but not surprised that his team discovered a simple, fundamental rule at the core of such a complex system as the brain, where 100 billion neurons each have thousands of ever-changing synapses. He likens it to how a massive school of fish can suddenly change direction, en masse, so long as the lead fish turns and every other fish obeys the simple rule of following the fish right in front of it.
"Collective behaviors of complex systems always have simple rules," said Sur, Paul E. and Lilah Newton Professor of Neuroscience in the Picower Institute and the department of Brain and Cognitive Sciences at MIT. "When one synapse goes up, within 50 micrometers there is a decrease in the strength of other synapses using a well-defined molecular mechanism."
This finding, he said, provides an explanation of how synaptic strengthening and weakening combine in neurons to produce plasticity.
Multiple manipulations
Though the rule they found was simple, the experiments that revealed it were not. As they worked to activate plasticity in the visual cortex of mice and then track how synapses changed to make that happen, lead authors Sami El-Boustani and Jacque Pak Kan Ip, postdoctoral researchers in Sur's lab, accomplished several firsts.
In one key experiment, they invoked plasticity by changing a neuron's "receptive field," or the patch of the visual field it responds to. Neurons receive input through synapses on little spines of their branch-like dendrites. To change a neuron's receptive field, the scientists pinpointed the exact spine on the relevant dendrite of the neuron, and then closely monitored changes in its synapses as they showed the mouse a target in a particular place on a screen that differed from the neuron's original receptive field. Whenever the target was in the new receptive field position they wanted to induce, they reinforced the neuron's response by flashing a blue light inside the mouse's visual cortex, instigating extra activity just like another neuron might. The neuron had been genetically engineered to be activated by light flashes, a technique called "optogenetics."
The researchers did this over and over. Because the light stimulation correlated with each appearance of the target in the new position in the mouse's vision, this caused the neuron to strengthen a particular synapse on the spine, encoding the new receptive field.
"I think it's quite amazing that we are able to reprogram single neurons in the intact brain and witness in the living tissue the diversity of molecular mechanisms that allows these cells to integrate new functions through synaptic plasticity," El-Boustani said.
As the synapse for the new receptive field grew, the researchers could see under the two-photon microscope that nearby synapses also shrank. They did not observe these changes in experimental control neurons that lacked the optogenetic stimulation.
But then they went further to confirm their findings. Because synapses are so tiny, they are near the limit of the resolution of light microscopy. So after the experiments the team dissected the brain tissues containing the dendrites of manipulated and control neurons and shipped them to co-authors at the Ecole Polytechnique Federal de Lausanne in Switzerland. They performed a specialized, higher-resolution, 3D electron microscope imaging, confirming that the structural differences seen under the two-photon microscope were valid.
"This is the longest length of dendrite ever reconstructed after being imaged in vivo," said Sur, who also directs the Simons Center for the Social Brain at MIT.
Of course, reprogramming a mouse's genetically engineered neuron with flashes of light is an unnatural manipulation, so the team did another more classic "monocular deprivation" experiment in which they temporarily closed one eye of a mouse. When that happens synapses in neurons related to the closed eye weaken and synapses related to the still open eye strengthen. Then when they reopened the previously closed eye, the synapses rearrange again. They tracked that action, too, and saw that as synapses strengthen, their immediate neighbors would weaken to compensate.
Solving the mystery of the Arc
Having seen the new rule in effect, the researchers were still eager to understand how neurons obey it. They used a chemical tag to watch how key "AMPA" receptors changed in the synapses and saw that synaptic enlargement and strengthening correlated with more AMPA receptor expression while shrinking and weakening correlated with less AMPA receptor expression.
The protein Arc regulates AMPA receptor expression, so the team realized they had to track Arc to fully understand what was going on. The problem, Sur said, is that no one had ever done that before in the brain of a live, behaving animal. So the team reached out to co-authors at the Kyoto University Graduate School of Medicine and the University of Tokyo, who invented a chemical tag that could do so.
Using the tag, the team could see that the strengthening synapses were surrounded with weakened synapses that had enriched Arc expression. Synapses with reduced amount of Arc were able to express more AMPA receptors whereas increased Arc in neighboring spines caused those synapses to express less AMPA receptors.
"We think Arc maintains a balance of synaptic resources," Ip said. "If something goes up, something must go down. That's the major role of Arc."
Sur said the study therefore solves a mystery of Arc: No one before had understood why Arc seemed to be upregulated in dendrites undergoing synaptic plasticity, even though it acts to weaken synapses, but now the answer was clear. Strengthening synapses increase Arc to weaken their neighbors.
Sur added that the rule helps explain how learning and memory might work at the individual neuron level because it shows how a neuron adjusts to the repeated simulation of another.
https://www.sciencedaily.com/releases/2018/06/180621141027.htm
Dementia can be caused by hypertension
June 13, 2018
Science Daily/Oxford University Press USA
A new study indicates that patients with high blood pressure are at a higher risk of developing dementia. This research also shows (for the first time) that an MRI can be used to detect very early signatures of neurological damage in people with high blood pressure, before any symptoms of dementia occur.
High blood pressure is a chronic condition that causes progressive organ damage. It is well known that the vast majority of cases of Alzheimer's disease and related dementia are not due to genetic predisposition but rather to chronic exposure to vascular risk factors.
The clinical approach to treatment of dementia patients usually starts only after symptoms are clearly evident. However, it has becoming increasingly clear that when signs of brain damage are manifest, it may be too late to reverse the neurodegenerative process. Physicians still lack procedures for assessing progression markers that could reveal pre-symptomatic alterations and identify patients at risk of developing dementia.
Researchers screened subjects admitted at the Regional Excellence Hypertension Center of the Italian Society of Hypertension in the Department of Angiocardioneurology and Translational Medicine of the I.R.C.C.S, Neuromed, in Italy. Researchers recruited people aged 40 to 65, compliant to give written informed consent and with the possibility to perform a dedicated 3 Tesla MRI scan.
This work was conducted on patients with no sign of structural damage and no diagnosis of dementia. All patients underwent clinical examination to determine their hypertensive status and the related target organ damage. Additionally, patients were subjected to an MRI scan to identify microstructural damage.
To gain insights in the neurocognitive profile of patients a specific group of tests was administered. As primary outcome of the study the researchers aimed at finding any specific signature of brain changes in white matter microstructure of hypertensive patients, associated with an impairment of the related cognitive functions.
The result indicated that hypertensive patients showed significant alterations in three specific white matter fiber-tracts. Hypertensive patients also scored significantly worse in the cognitive domains ascribable to brain regions connected through those fiber-tracts, showing decreased performances in executive functions, processing speed, memory and related learning tasks.
Overall, white matter fiber-tracking on MRIs showed an early signature of damage in hypertensive patients when otherwise undetectable by conventional neuroimaging. As these changes can be detected before patients show symptoms, these patients could be targeted with medication earlier to prevent further deterioration in brain function. These findings are also widely applicable to other forms of neurovascular disease, where early intervention could be of marked therapeutic benefit.
"The problem is that neurological alterations related to hypertension are usually diagnosed only when the cognitive deficit becomes evident, or when traditional magnetic resonance shows clear signs of brain damage. In both cases, it is often too late to stop the pathological process" said Giuseppe Lembo, the coordinator of this study.
"We have been able to see that, in the hypertensive subjects, there was a deterioration of white matter fibers connecting brain areas typically involved in attention, emotions and memory, said Lorenzo Carnevale, IT engineer and first author of the study. "An important aspect to consider is that all the patients studied did not show clinical signs of dementia and, in conventional neuroimaging, they showed no signs of cerebral damage. Of course, further studies will be necessary, but we think that the use of tractography will lead to the early identification of people at risk of dementia, allowing timely therapeutic interventions."
https://www.sciencedaily.com/releases/2018/06/180613101925.htm
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