Little or poor sleep may be associated with worse brain function when aging

Research published today in PLOS ONE by researchers at the University of Warwick indicates that sleep problems are associated with worse memory and executive function in older people.

Analysis of sleep and cognitive (brain function) data from 3,968 men and 4,821 women who took part in the English Longitudinal Study of Ageing (ELSA), was conducted in a study funded by the Economic and Social Research Council (ESRC). Respondents reported on the quality and quantity of sleep over the period of a month.

The study showed that there is an association between both quality and duration of sleep and brain function which changes with age.

In adults aged between 50 and 64 years of age, short sleep (<6hrs per night) and long sleep (>8hrs per night) were associated with lower brain function scores. By contrast, in older adults (65-89 years) lower brain function scores were only observed in long sleepers.

Dr Michelle A Miller says “6-8 hours of sleep per night is particularly important for optimum brain function, in younger adults”. These results are consistent with our previous research, which showed that 6-8 hours of sleep per night was optimal for physical health, including lowest risk of developing obesity, hypertension, diabetes, heart disease and stroke”.

Interestingly, in the younger pre-retirement aged adults, sleep quality did not have any significant association with brain function scores, whereas in the older adults (>65 years), there was a significant relationship between sleep quality and the observed scores.

“Sleep is important for good health and mental wellbeing” says Professor Francesco Cappuccio, “Optimising sleep at an older age may help to delay the decline in brain function seen with age, or indeed may slow or prevent the rapid decline that leads to dementia”.

Dr Miller concludes that “if poor sleep is causative of future cognitive decline, non-pharmacological improvements in sleep may provide an alternative low-cost and more accessible Public Health intervention, to delay or slow the rate of cognitive decline”.

Researchers publish one of the longest longitudinal studies of cognition in MS

Researchers at Kessler Foundation and the Cleveland Clinic have published one of the longest longitudinal studies of cognition in multiple sclerosis (MS). The article, “Cognitive impairment in multiple sclerosis: An 18-year follow-up study,” was epublished by Multiple Sclerosis and Related Disorders on April 13, 2014. Results provide insight into the natural evolution of cognitive changes over time, an important consideration for researchers and clinicians. Authors are Lauren B. Strober, PhD, of Kessler Foundation and  Stephen M. Rao, PhD, Jar-Chi Lee, Elizabeth Fisher, PhD, and Richard Rudick, MD, of the Cleveland Clinic.

“While cognitive impairment is known to affect 40 to 65% of individuals with MS, few studies have followed the pattern of cognitive decline over time, which is important for understanding long-term care and outcomes associated with MS,” said Dr. Strober, senior research scientist at Kessler Foundation. “Our study was based on a unique sample of 22 patients who underwent neuropsychological testing at entry into the original phase 3 clinical trial of intramuscular interferon beta-1a, and again at 18-year followup.”

At baseline, 9 patients (41%) had cognitive impairment; at 18-year followup, 13 patients (59%), were found to be impaired. Significant declines over time were found in information processing speed, auditory attention, memory, episodic learning and visual construction. Decline was steeper in the unimpaired than in the impaired group, as indicated by the Symbol Digit Modalities Test (SDMT).

"These longitudinal data contribute substantially to our knowledge of the course of cognitive decline in MS,” noted John DeLuca, PhD, VP of Research & Training at Kessler Foundation. “In light of the young age at diagnosis, this perspective is fundamental to the development of rehabilitation strategies that meet the needs of people dealing with the cognitive effects of MS.”

The study was funded by Biogen Idec.

Poor cardiovascular health linked to memory, learning deficits

The risk of developing cognitive impairment, especially learning and memory problems, is significantly greater for people with poor cardiovascular health than people with intermediate or ideal cardiovascular health, according to a study in the Journal of the American Heart Association.

Cardiovascular health plays a critical role in brain health, with several cardiovascular risk factors also playing a role in higher risk for cognitive decline.

Researchers found that people with the lowest cardiovascular health scores were more likely have impairment on learning, memory and verbal fluency tests than their counterparts with intermediate or better risk profiles.

The study involved 17,761 people aged 45 and older at the outset who had normal cognitive function and no history of stroke. Mental function was evaluated four years later.

Researchers used data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to determine cardiovascular health status based on The American Heart Association Life’s Simple 7™ score. The REGARDS study population is 55 percent women, 42 percent blacks, 58 percent whites and 56 percent are residents of the “stroke belt” states of Alabama, Arkansas, Georgia, Louisiana, Mississippi, North Carolina, South Carolina and Tennessee.

The Life’s Simple 7™ initiative is a new system to measure the benefits of modifiable health behaviors and risk factors in cardiovascular health, such as smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. It classifies each of the seven factors of heart health as either poor, intermediate or ideal.

After accounting for differences in age, sex, race and education, researchers identified cognitive impairment in:

• 4.6 percent of people with the worst cardiovascular health scores;
• 2.7 percent of those with intermediate health profiles; and
• 2.6 percent of those in the best cardiovascular health category.

“Even when ideal cardiovascular health is not achieved intermediate levels of cardiovascular health are preferable to low levels for better cognitive function,” said lead investigator Evan L. Thacker, Ph.D., an assistant professor and chronic disease epidemiologist at Brigham Young University Department of Health Science, in Provo, Utah.

“This is an encouraging message because intermediate cardiovascular health is a more realistic target for many individuals than ideal cardiovascular health.”

The differences were seen regardless of race, gender, pre-existing cardiovascular conditions, or geographic region, although higher cardiovascular health scores were more common in men, people with higher education, higher income, and among people without any cardiovascular disease.

Cognitive function assessments involved tests to measure verbal learning, memory and fluency. Verbal learning was determined using a three-trial, ten-item word list, while verbal memory was assessed by free recall of the ten-item list after a brief delay filled with non-cognitive questions. Verbal fluency was determined by asking each participant to name as many animals as possible in 60 seconds.

Although mechanisms that might explain the findings remain unclear, Thacker said that undetected subclinical strokes could not be ruled out.

Brain inflammation a recipe for chronic fatigue

Patients with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis, experience severe and often disabling exhaustion. Other symptoms include cognitive dysfunction, pain and depression. Although brain inflammation is thought to be involved in the development of these symptoms, direct evidence of this relationship has proved elusive. 

Yasuyoshi Watanabe, Yasuhito Nakatomi, Kei Mizuno and colleagues from the RIKEN Center for Life Science Technologies and other institutes in Japan have now shown using a noninvasive brain imaging technique that the neuropsychological symptoms of patients with CFS are closely associated with widespread inflammation in the brain.

Positron emission tomography (PET) is a brain imaging technique that uses radioactive tracers attached to particular cell types or molecules to noninvasively track changes in the brain in disease states. To examine the effect of CFS, the researchers used a radioactive tracer that labels activated glial cells, which tend to be associated with neuroinflammation. They performed PET imaging studies on nine CFS sufferers and ten healthy individuals to identify the extent to which brain inflammation plays a role in CFS. They found that the levels of tracer binding were much higher in multiple brain regions in the CFS patients compared with the same brain regions in the healthy participants.

The investigation also found correlations between tracer binding in various brain regions and the severity of symptoms in the CFS patients. The researchers found that inflammation in the thalamus—a region of the brain responsible for relaying motor and sensory information to and from the cerebral cortex—correlated with the severity of both cognitive impairment and pain in the CFS patients. They also identified a correlation between inflammation in the amygdala—a part of the brain linked to emotional memory—and the severity of cognitive impairment. The severity of depression in CFS patients, on the other hand, was linked to the extent of inflammation in the hippocampus, which is a part of the brain known to be associated with depression.

The findings suggest that inflammation in the brain plays a key role in CFS in humans. Drugs that fight inflammation in the brain may therefore offer promising therapies to prevent or treat CFS and its related symptoms of pain, depression and cognitive dysfunction.

“Because CFS is diagnosed based on subjective symptoms such as fatigue, pain, sleep problems and cognitive impairment,” says Mizuno, “neuroinflammation as observed by PET imaging could be helpful as a more objective biomarker for diagnosis of the disorder.”

(Image caption: A solar flare erupts on the far right side of the sun, in this image captured by NASA’s Solar Dynamics Observatory. The flare peaked at 6:34 p.m. EDT on March 12, 2014. Credit: NASA)

Some Astronauts at Risk for Cognitive Impairment

Johns Hopkins scientists report that rats exposed to high-energy particles, simulating conditions astronauts would face on a long-term deep space mission, show lapses in attention and slower reaction times, even when the radiation exposure is in extremely low dose ranges.

The cognitive impairments — which affected a large subset, but far from all, of the animals — appear to be linked to protein changes in the brain, the scientists say. The findings, if found to hold true in humans, suggest it may be possible to develop a biological marker to predict sensitivity to radiation’s effects on the human brain before deployment to deep space. The study, funded by NASA’s National Space Biomedical Research Institute, is described in the April issue of the journal Radiation Research.

When astronauts are outside of the Earth’s magnetic field, spaceships provide only limited shielding from radiation exposure, explains study leader Robert D. Hienz, Ph.D., an associate professor of behavioral biology at the Johns Hopkins University School of Medicine. If they take space walks or work outside their vehicles, they will be exposed to the full effects of radiation from solar flares and intergalactic cosmic rays, he says, and since neither the moon nor Mars have a planet-wide magnetic field, astronauts will be exposed to relatively high radiation levels, even when they land on these surfaces.

But not everyone will be affected the same way, his experiments suggest. “In our radiated rats, we found that 40 to 45 percent had these attention-related deficits, while the rest were seemingly unaffected,” Hienz says. “If the same proves true in humans and we can identify those more susceptible to radiation’s effects before they are harmfully exposed, we may be able to mitigate the damage.”

If a biomarker can be identified for humans, it could have even broader implications in determining the best course of treatment for patients receiving radiotherapy for brain tumors or identifying which patients may be more at risk from radiation-based medical treatments, the investigators note.

Previous research has tested how well radiation-exposed rats do with basic learning tasks and mazes, but this new Johns Hopkins study focused on tests that closely mimic the self-tests of fitness for duty currently used by astronauts on the International Space Station prior to mission-critical events such as space walks. Similar fitness tests are also used for soldiers, airline pilots and long-haul truckers.

In one such test, an astronaut sees a blank screen on a handheld device and is instructed to tap the screen when an LED counter lights up. The normal reaction time should be less than 300 milliseconds. The rats in the experiment are similarly taught to touch a light-up key with their noses and are then tested to see how quickly they react.

To conduct the new study, rats were first trained for the tests and then taken to Brookhaven National Laboratory on Long Island in Upton, N.Y., where a collider produces the high-energy proton and heavy ion radiation particles that normally occur in space. The rats’ heads were exposed to varying levels of radiation that astronauts would normally receive during long-duration missions, while other rats were given sham exposures.

Once the rats returned to Johns Hopkins, they were tested every day for 250 days. The radiation-sensitive animals (19 of 46) all showed evidence of impairment that began at 50 to 60 days post–exposure and remained through the end of the study.

Lapses in attention occurred in 64 percent of the sensitive animals, elevations in impulsive responding occurred in 45 percent and slower reaction times occurred in 27 percent. The impairments were not dependent on radiation dose. Additionally, some of the rats didn’t recover at all from their deficits over time, while others showed some recovery over time.

The radiation-sensitive rats that received higher doses of radiation had a higher concentration of transporters for the neurotransmitter dopamine, which plays a role in vigilance and attention, says Catherine M. Davis, Ph.D., a postdoctoral fellow in the Department of Psychiatry and Behavioral Sciences and the study’s first author.

The dopamine transport system appears impaired in radiation-sensitive rats because the neurotransmitter is most likely not removed in the manner it should be for the brain to function properly, she says. Humans with genetic differences related to dopamine transport, she adds, have been shown to do worse on the type of mental fitness tests given to the astronauts and rats alike.

Davis says she wouldn’t want to see radiation-sensitive astronauts kept from future missions to the moon or Mars, but she would want those astronauts to be prepared to take special precautions to protect their brains, such as wearing extra shielding or not performing space walks.

“As with other areas of personalized medicine, we would seek to create individual treatment and prevention plans for astronauts we believe would be more susceptible to cognitive deficits from radiation exposure,” she says.

Current astronauts are not as exposed to the damaging effects of radiation, Davis says, because the International Space Station flies in an orbit low enough that the Earth’s magnetic field continues to provide protection.

While the Johns Hopkins team studies the likely effects of radiation on the brain during a deep space mission, other NASA-funded research groups are looking at the potential effects of radiation on other parts of the body and on whether it increases cancer risks.

Study Examines Vitamin D Deficiency and Cognition Relationship

Vitamin D deficiency and cognitive impairment are common in older adults, but there isn’t a lot of conclusive research into whether there’s a relationship between the two.

A new study from Wake Forest Baptist Medical Center published online ahead of print this month in the Journal of the American Geriatrics Society enhances the existing literature on the subject.

“This study provides increasing evidence that suggests there is an association between low vitamin D levels and cognitive decline over time,” said lead author Valerie Wilson, M.D., assistant professor of geriatrics at Wake Forest Baptist. “Although this study cannot establish a direct cause and effect relationship, it would have a huge public health implication if vitamin D supplementation could be shown to improve cognitive performance over time because deficiency is so common in the population.”

Wilson and colleagues were interested in the association between vitamin D levels and cognitive function over time in older adults. They used data from the Health, Aging and Body composition (Health ABC) study to look at the relationship. The researchers looked at 2,777 well-functioning adults aged 70 to 79 whose cognitive function was measured at the study’s onset and again four years later. Vitamin D levels were measured at the 12-month follow-up visit.

The Health ABC study cohort consists of 3,075 Medicare-eligible, white and black, well-functioning, community-dwelling older adults who were recruited between April 1997 and June 1998 from Pittsburgh, Pa., and Memphis, Tenn.

“With just the baseline observational data, you can’t conclude that low vitamin D causes cognitive decline. When we looked four years down the road, low vitamin D was associated with worse cognitive performance on one of the two cognitive tests used,” Wilson said. “It is interesting that there is this association and ultimately the next question is whether or not supplementing vitamin D would improve cognitive function over time.”

Wilson said randomized, controlled trials are needed to determine whether vitamin D supplementation can prevent cognitive decline and definitively establish a causal relationship.

“Doctors need this information to make well-supported recommendations to their patients,” Wilson said. “Further research is also needed to evaluate whether specific cognitive domains, such as memory versus concentration, are especially sensitive to low vitamin D levels.”

(Image caption: Blockade of p25 generation in the brain of an Alzheimer’s disease mouse model mitigates amyloid plaque buildup. Hippocampal slices from a seven-month-old 5XFAD mouse (left) or 5XFAD;p35KI mouse (right), alongside markers for Aβ (red) and activated astrocyte (green). Nuclei are shown in blue.)

Neuroscientists find that limiting a certain protein in the brain reverses Alzheimer’s symptoms in mice

Limiting a certain protein in the brain reverses Alzheimer’s symptoms in mice, report neuroscientists at MIT’s Picower Intitute for Learning and Memory.

Researchers found that the overproduction of the protein known as p25 may be the culprit behind the sticky protein-fragment clusters that build up in the brains of Alzheimer’s patients. The work, which was published in the April 10 issue of Cell, could provide a new drug target for the treatment of the disease that affects more than five million Americans, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and senior author of the paper.

Abnormal clusters of protein fragments, known as beta amyloid plaques, are believed to cause the cognitive impairments, cell death, and tissue loss associated with Alzheimer’s. The p25 protein had been tied to the creation and buildup of beta amyloids, but until now, p25’s role in Alzheimer’s pathology was not well understood.

“This protein appears to help maintain normal brain activity, but also is part of a feedback loop with beta amyloids. It generates the plaques which, in turn, boost levels of p25,” Tsai says.

Lead author of the paper is Jinsoo Seo, a postdoc associate at the Picower Institute.

The benefits of p25 generation

Elevated p25 levels in the brain have been documented upon exposure to neurotoxic stimuli such as oxidative stress and beta amyloids.

“In this study, for the first time we show that a variety of physiological neuronal activities generate p25 in the hippocampus, where memories are encoded in the brain,” Tsai says.

To delineate the precise roles of p25, Tsai’s lab generated a transgenic mouse model, which enabled researchers to prevent the production of p25 without altering other proteins with essential roles in brain development.

The researchers found that p25 is required for synaptic plasticity, the ability of brain connections to change over time; especially for the process called long-term depression (LTD) that selectively weakens sets of synapses and is associated with memory extinction.

Tsai’s team observed that the mice unable to generate p25 could learn new tasks and form memories normally; however, when the researchers began to address memory extinction, they soon noticed that the mice have difficulties with replacing older memories with newer ones.

Too much of a good thing

“This finding not only boosts our understanding of p25 in synaptic functions, but also explains the underlying mechanism of the inordinate synaptic depression observed in the Alzheimer’s brain,” Seo says.

“This finding led us to question whether the blockade of p25 generation could mitigate pathological phenotypes in the Alzheimer’s brain,” Tsai says.

In the mouse model of Alzheimer’s disease, inhibiting p25 production improved cognitive function, greatly reduced plaque formation and neuroinflammation, hallmark features of Alzheimer’s disease.

These results hold out the hope that a drug that regulates p25 could benefit Alzheimer’s disease patients by improving cognitive function and perhaps delaying the development of brain pathology, Tsai says.

Study debunks alcohol consumption assertions

ALCOHOL consumption is not a direct cause of cognitive impairment in older men later in life, a study conducted by the University of Western Australia has found. 

The study, published in the Journal of Neurology, used Mendelian randomisation to analyse the genetic data from 3,542 men between the ages of 65 and 83 years. 

The scientists measured the participants’ cognitive function three to eight years after recording their alcohol consumption. 

Lead author, Western Australian Centre for Health and Ageing Director and UWA Professor Osvaldo Almeida says the team investigated the triangular association between alcohol consumption, cognitive impairment and a genetic polymorphism that modulates the efficiency of a critical enzyme of alcohol metabolism. 

“We found a genetic variation that increases absenteeism and decreases the total amount of alcohol consumed,” Prof Almeida says.

“If alcohol were a cause of cognitive impairment, one would expect that this genetic variation would be associated with lower risk of cognitive impairment in later life [because people with this genetic variation drink less or not at all]. 

“That was not the case. Hence, we concluded that the association between alcohol use and cognitive impairment is not due to a direct effect of alcohol.”

The study also presented results that are consistent with the possibility, but do not necessarily prove, that regular moderate drinking decreases the risk of cognitive impairment in older men.

Prof Almeida says the reasons for these results were unclear.

“But evidence from a randomised trial looking at the effect of the Mediterranean diet [which includes nuts, olive oil, vegetables and wine] on health outcomes is supportive of this hypothesis,” he says. 

“One may argue that people who drink in moderation have a lifestyle where, in general, things are done in moderation. 

“This approach to life may decrease health hazards in general.”

Prof Almeida says that although the results didn’t show alcohol affecting cognitive impairment, other studies have found excessive alcohol use to be associated with worse physical health, widowhood and poor social support. 

“[These studies] led to the assumption that alcohol must directly damage the brain and cause cognitive impairment,” he says. 

“This study shows that such an assumption is wrong. 

“It also suggests that alcohol may have a small protective effect that we need to understand better in order to develop new interventions that might contribute to prevent dementia without all the bad outcomes associated with alcohol.”

Protein reelin rescues cognitive impairment in animal models of Alzheimer’s disease

The scientists Eduardo Soriano and Lluís Pujadas, from the University of Barcelona (UB), and the “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CIBERNED) have led research into the role of reelin in animal models of Alzheimer’s disease.

Published today in the journal Nature Communications, the study demonstrates how an increase in the levels of reelin—a protein that is essential for cerebral cortex plasticity—has the capacity to restore cognitive capacity in mouse models of Alzheimer’s disease, delaying amyloid-beta (Αβ) fibril formation in vitro and reducing the accumulation of amyloid deposits in the brains of animals affected by this disease.

The study, which was started four years ago, has involved the collaboration of members of the Peptides and Proteins lab at the Institute for Research in Biomedicine (IRB), namely Bernat Serra-Vidal, PhD student, Ernest Giralt, group leader, and Natàlia Carulla, associate researcher whose investigation focuses on the aggregation of Αβ. Alzheimer’s disease, which affects approximately 500,000 people in Spain, is characterised by the loss of neural connections and by neuronal death, both associated mainly with the formation of senile plaques (extracellular deposits of Aβ) and the presence of neurofibrillary tangles (intracellular deposits of tau protein.

In the IRB lab, researchers have performed experiments in vitro to determine whether there is an interaction between Aβ aggregation and reelin. These assays have revealed that reelin interacts with the Aβ peptide, delaying the formation of Aβ fibrils until it is trapped within them. “When reelins becomes trapped in Aβ fibrils, it loses its capacity to strengthen synaptic plasticity. This explains why an increase in reelin expression in the brain may be beneficial,” explain the authors of the study.

The hypotheses from the work in vitro have been tested in vivo using experimental animals. This study is the first to demonstrate a neuroprotective effect of reelin in neurodegenerative disease and, in addition, offers a possible explanation for this protective role.

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