Autism's social deficits are reversed by an anti-cancer drug

Of all the challenges that come with a diagnosis of autism spectrum disorder (ASD), the social difficulties are among the most devastating. Currently, there is no treatment for this primary symptom of ASD. New research at the University at Buffalo reveals the first evidence that it may be possible to use a single compound to alleviate the behavioral symptoms by targeting sets of genes involved in the disease.

The research, published today in Nature Neuroscience, demonstrated that brief treatment with a very low dose of romidepsin, a Food and Drug Administration-approved anti-cancer drug, restored social deficits in animal models of autism in a sustained fashion.

The three-day treatment reversed social deficits in mice deficient in a gene called Shank 3, an important risk factor for ASD. This effect lasted for three weeks, spanning the juvenile to late adolescent period, a critical developmental stage for social and communication skills. That is equivalent to several years in humans, suggesting the effects of a similar treatment could potentially be long-lasting, the researchers say.

Profound, prolonged effect

"We have discovered a small molecule compound that shows a profound and prolonged effect on autism-like social deficits without obvious side effects, while many currently used compounds for treating a variety of psychiatric diseases have failed to exhibit the therapeutic efficacy for this core symptom of autism," said Zhen Yan, PhD, professor in the Department of Physiology and Biophysics in the Jacobs School of Medicine and Biomedical Sciences at UB, and senior author on the paper.

The study builds on her previous research from 2015. That work revealed how the loss of Shank 3 disrupts neuronal communications by affecting the function of the NMDA (n-methyl-D-aspartate) receptor, a critical player in regulating cognition and emotion, leading to deficits in social preference that are common in ASD.

In the new research, the UB scientists found they could reverse those social deficits with a very low dose of romidepsin, which, they found, restores gene expression and function using an epigenetic mechanism, where gene changes are caused by influences other than DNA sequences. Yan noted that human genetics studies have suggested that epigenetic abnormalities likely play a major role in ASD.

To pursue these promising findings, Yan has founded a startup company called ASDDR, which was awarded a Small Business Technology Transfer grant from the National Institutes of Health last summer for more than $770,000.

Epigenetics in ASD

Many of the mutations in ASD, Yan explained, result from chromatin remodeling factors, which are involved in dynamically changing the structure of chromatin, the complex of genetic material in the cell nucleus that condenses into chromosomes.

"The extensive overlap in risk genes for autism and cancer, many of which are chromatin remodeling factors, supports the idea of repurposing epigenetic drugs used in cancer treatment as targeted treatments for autism," said Yan.

She and her colleagues knew that chromatin regulators -- which control how genetic material gains access to a cell's transcriptional machinery -- were key to treating the social deficits in ASD, but the challenge was to know how to affect key risk factors at once.

"Autism involves the loss of so many genes," Yan explained. "To rescue the social deficits, a compound has to affect a number of genes that are involved in neuronal communication."

To do so, the team turned to a type of chromatin remodeler called histone modifiers. They modify proteins called histones that help organize genetic material in the nucleus so gene expression can be regulated. Since many genes are altered in autism, the UB scientists knew a histone modifier might be effective.

Loosening up chromatin

In particular, they were interested in histone deacetylase (HDAC), a family of histone modifiers that are critically involved in the remodeling of chromatin structure and the transcriptional regulation of targeted genes.

"In the autism model, HDAC2 is abnormally high, which makes the chromatin in the nucleus very tight, preventing genetic material from accessing the transcriptional machinery it needs to be expressed," said Yan. "Once HDAC2 is upregulated, it diminishes genes that should not be suppressed, and leads to behavioral changes, such as the autism-like social deficits."

But the anti-cancer drug romidepsin, a highly potent HDAC inhibitor, turned down the effects of HDAC2, allowing genes involved in neuronal signaling to be expressed normally.

"The HDAC inhibitor loosens up the densely packed chromatin so that the transcriptional machinery gains access to the promoter area of the genes; thus they can be expressed," Yan said.

The rescue effect on gene expression was widespread. When Yan and her co-authors conducted genome-wide screening at the Genomics and Bioinformatics Core at UB's New York State Center of Excellence in Bioinformatics and Life Sciences, they found that romidepsin restored the majority of the more than 200 genes that were suppressed in the autism animal model they used.

"The advantage of being able to adjust a set of genes identified as key autism risk factors may explain the strong and long-lasting efficacy of this therapeutic agent for autism." Yan explained. She and her colleagues will continue their focus on discovering and developing better therapeutic agents for autism.

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Story Source:

Materials provided by University at Buffalo. Original written by Ellen Goldbaum. Note: Content may be edited for style and length.

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Journal Reference:

1. Luye Qin, Kaijie Ma, Zi-Jun Wang, Zihua Hu, Emmanuel Matas, Jing Wei, Zhen Yan. Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition. Nature Neuroscience, 2018; DOI: 10.1038/s41593-018-0110-8

Study suggests method to boost growth of blood vessels and muscle

Activating proteins linked to longevity may help to increase endurance and combat frailty in the elderly

As we get older, our endurance declines, in part because our blood vessels lose some of their capacity to deliver oxygen and nutrients to muscle tissue. An MIT-led research team has now found that it can reverse this age-related endurance loss in mice by treating them with a compound that promotes new blood vessel growth.

The study found that the compound, which re-activates longevity-linked proteins called sirtuins, promotes the growth of blood vessels and muscle, boosting the endurance of elderly mice by up to 80 percent.

If the findings translate to humans, this restoration of muscle mass could help to combat some of the effects of age-related frailty, which often lead to osteoporosis and other debilitating conditions.

"We'll have to see if this plays out in people, but you may actually be able to rescue muscle mass in an aging population by this kind of intervention," says Leonard Guarente, the Novartis Professor of Biology at MIT and one of the senior authors of the study. "There's a lot of crosstalk between muscle and bone, so losing muscle mass ultimately can lead to loss of bone, osteoporosis, and frailty, which is a major problem in aging."

The first author of the paper, which appears in Cell on March 22, is Abhirup Das, a former postdoc in Guarente's lab who is now at the University of New South Wales in Australia. Other senior authors of the paper are David Sinclair, a professor at Harvard Medical School and the University of New South Wales, and Zolt Arany, a professor at the University of Pennsylvania.

Race against time

In the early 1990s, Guarente discovered that sirtuins, a class of proteins found in nearly all animals, protect against the effects of aging in yeast. Since then, similar effects have been seen in many other organisms.

In their latest study, Guarente and his colleagues decided to explore the role of sirtuins in endothelial cells, which line the inside of blood vessels. To do that, they deleted the gene for SIRT1, which encodes the major mammalian sirtuin, in endothelial cells of mice. They found that at 6 months of age, these mice had reduced capillary density and could run only half as far as normal 6-month-old mice.

The researchers then decided to see what would happen if they boosted sirtuin levels in normal mice as they aged. They treated the mice with a compound called NMN, which is a precursor to NAD, a coenzyme that activates SIRT1. NAD levels normally drop as animals age, which is believed to be caused by a combination of reduced NAD production and faster NAD degradation.

After 18-month-old mice were treated with NMN for two months, their capillary density was restored to levels typically seen in young mice, and they experienced a 56 to 80 percent improvement in endurance. Beneficial effects were also seen in mice up to 32 months of age (comparable to humans in their 80s).

"In normal aging, the number of blood vessels goes down, so you lose the capacity to deliver nutrients and oxygen to tissues like muscle, and that contributes to decline," Guarente says. "The effect of the precursors that boost NAD is to counteract the decline that occurs with normal aging, to reactivate SIRT1, and to restore function in endothelial cells to give rise to more blood vessels."

These effects were enhanced when the researchers treated the mice with both NMN and hydrogen sulfide, another sirtuin activator.

Benefits of exercise

The researchers also found that SIRT1 activity in endothelial cells is critical for the beneficial effects of exercise in young mice. In mice, exercise generally stimulates growth of new blood vessels and boosts muscle mass. However, when the researchers knocked out SIRT1 in endothelial cells of 10-month-old mice, then put them on a four-week treadmill running program, they found that the exercise did not produce the same gains seen in normal 10-month-old mice on the same training plan.

If validated in humans, the findings would suggest that boosting sirtuin levels may help older people retain their muscle mass with exercise, Guarente says. Studies in humans have shown that age-related muscle loss can be partially staved off with exercise, especially weight training.

"What this paper would suggest is that you may actually be able to rescue muscle mass in an aging population by this kind of intervention with an NAD precursor," Guarente says.

In 2014, Guarente started a company called Elysium Health, which sells a dietary supplement containing a different precursor of NAD, known as NR, as well as a compound called pterostilbene, which is an activator of SIRT1.

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Story Source:

Materials provided by Massachusetts Institute of Technology. Original written by Anne Trafton. Note: Content may be edited for style and length.

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Journal Reference:

1. Abhirup Das, George X. Huang, Michael S. Bonkowski, Alban Longchamp, Catherine Li, Michael B. Schultz, Lynn-Jee Kim, Brenna Osborne, Sanket Joshi, Yuancheng Lu, Jose Humberto Treviño-Villarreal, Myung-Jin Kang, Tzong-tyng Hung, Brendan Lee, Eric O. Williams, Masaki Igarashi, James R. Mitchell, Lindsay E. Wu, Nigel Turner, Zolt Arany, Leonard Guarente, David A. Sinclair. Impairment of an Endothelial NAD -H 2 S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 2018; 173 (1): 74 DOI: 10.1016/j.cell.2018.02.008

Perfecting The Rep

Improving your muscle-building results doesn’t necessarily mean assembling a larger repertoire — adding more and more exercises to your toolbox until you’re hopelessly inundated. To accelerate your progress, you just need perfection — at least when it comes to your repetitions.

One repetition of an exercise consists of the following: a concentric (positive) contraction where your muscles shorten to move a load, an isometric (paused) contraction where you hold the weight in place, and an eccentric (negative) contraction where the muscles lengthen against resistance. An ideal repetition demands perfection in all three of these zones.

These simple, practical directives can help you perfect your reps from start to finish. Implement them and you could and draw big dividends from your current workout routine — starting right now.

Going Up: The Concentric Portion

There is a lot of confusion as to how to execute a proper concentric contraction when it comes to reps and poundage, and although some people argue that you have to lift heavy for fewer reps to incite change, others rally for lighter loads to failure. In truth, there is no magical rep range for maximizing muscle size, and according to research published in the Journal of Applied Physiology, lifting a lighter load to failure produces muscular gains similar to those produced by lifting a heavy load to failure.

Therefore, you can incorporate both kinds of sets into your programming so long as you reach muscular failure with each set. To keep things fresh, try using both techniques within the same workout, or alternate between them every other session.

Heavy Loads (1 to 5 reps)

When lifting a load that is heavy relative to your strength, focus on exploding into the concentric portion of each rep. In other words, rather than simply picking the weight up off the floor for a deadlift, get into position, take the slack out of the bar, then “rip” it off the ground as fast as you can without sacrificing technique. For a bench press, get into position, lower the bar, then drive it up off your chest as fast as you can. This technique — combined with the heavy load — improves strength and power, which over time allows you to lift more weight and therefore incur bigger gains.

Lighter Loads (6 to 20+ reps)

Hypertrophy is all about controlling the weight throughout the entire range of motion, so with that in mind, it is not advised to explode into the concentric portion with a lighter load, as you might actually lose control of your equipment.

For each lighter-load rep, take at least two full counts to move the weight to the peak contraction. This engages more fibers in the target muscles, and eliminates the use of momentum, which can divert work to other muscle groups.

Going Down: The Eccentric Portion

Your muscles are stronger during a negative, or eccentric, contraction of a lift, so if you let the weight come crashing down rather than harnessing that power, you’re losing out on some serious building potential — and putting yourself at risk for injury.

Go slow to grow

According to research, a slow, four-second eccentric contraction during biceps curls produced superior increases in growth than did a one-second eccentric action, because it increased the muscular time under tension.

Likely, you believe you’re already performing a slow eccentric contraction, but it’s probably not slow enough. Take this challenge: Set a timer nearby where you can see it. Lift the weight, then deliberately lower it for four to six full seconds. We bet it’s longer than you imagined.

Be a control freak

Although it might be tempting to lift super heavy to take advantage of the building benefits of eccentric contractions, listen up: An overly heavy weight can create forces that exceed the structural integrity of your joints, tendons and ligaments and could lead to serious injury such as sprains, strains and even tears. Rather than going super heavy, simply increase your time under tension (see above) to incite the same kind of growth without the risk.

THE CHEATING CAVEAT

Not all cheating is off limits. In fact, once you have the fundamentals down pat, there are some solid ways to cheat effectively. For instance, cheat reps that use non-targeted muscles to help lift a weight through the positive contraction increases your time under tension of that targeted muscle, and allows you to take advantage of the negative portion of the rep to boost your building potential.

In a dumbbell biceps curl, for example, once you have no more strict reps left in your tank, use your lower body — not your back, shoulders or arms — to cheat. Perform a quarter squat, making sure your spine and core are stable and strong, then quickly extend your legs and hips and use that momentum to help you lift the dumbbells through the concentric portion to the top, then slowly lower them for four to six seconds through the eccentric until you reach the bottom. Repeat until you can no longer maintain proper posture and/or form — then you’re done.

Hold It: Isometrics for Growth

A simple (but not easy) way to increase the difficulty of a move is to incorporate an isometric hold — pausing for roughly one to three seconds at the aspect of the exercise you find to be the most challenging. This will help improve strength and endurance in the moves and movement patterns you want to improve.

Where

Where you perform the hold depends on the exercise you’re doing. For example, in a bench press or squat, holding at the bottom of the move proves the most difficult, whereas with a barbell or machine row the hardest part is at the peak contraction. For a standing move such as a biceps curl, an isometric hold in the middle of the range of motion, when your forearm is parallel to the floor, is brutal.

When

You can also add a longer isometric hold at the beginning or end of a set to increase your time under tension. For example, at the end of a set of pull-ups, you’d hold at the top of the range of motion (the contracted position) for up to 10 seconds. However, in a bench press — where the most difficult part is holding the bar just above your chest — the isometric hold would come at the beginning of a set for safety; at the end, you might be too fatigued to press the weight back up.

PERFECTION SABOTEURS

Lots of factors can prevent you from executing a perfect rep. Here are the top three offenders that happen every day in every gym in every country on the planet.

No. 1: Going too heavy

At any given time at a big-box gym, you’ll see at least one person seesawing during a biceps curl or lateral raise, throwing his or her back into each and every rep, clearly lifting with ego more than muscle. Although it might look “cool” to a newbie, to the rest of us, it is ludicrous.

When you lift too heavy, you reduce your time under mechanical tension because you’re forced to use momentum. You’re also unable to perform a controlled negative without compromising your joints and you use more muscles than you intended to target, reducing the accumulated pump (i.e., metabolic stress).

No. 2: Improper positioning and posture

When you lift weights, do you look like a droopy question mark, with stooped shoulders, a rounded spine and a lax core? This position puts you at risk for injury and reduces the effectiveness of a move.

NFL coaches have a saying that applies to strength training: “Stance, alignment, assignment.” Think of that when you prepare to execute a movement. First, make sure you’re standing, lying or sitting properly for your exercise. Next, check your spinal and body alignment from head to heels. Finally, being mindful of those first two checkpoints, go for it.

No. 3: Lifting without focus

These days there are endless things to distract you from your intention, whether it’s social media or socializing. But if you’re not connecting mentally as well as physically to the exercise you’re doing, you’re shortchanging your results. Research published in the Strength and Conditioning Journal showed that mentally concentrating on the target musculature resulted in greater activation of that muscle group.

Deliberately focus on each and every rep you’re executing, and feel the muscle contracting in both directions. Wear headphones to tune out the gym kerfuffle, and extricate yourself from your phone, leaving it in the car or locker — Twitter can wait.

Could sugar chains be the answer to bone growth in osteoporosis?

Scientists at the University of York have shown that altering the structure of sugar chains on the surface of stem cells could help promote bone growth in the body.

The discovery could have important implications for future treatments of osteoporosis, a condition that affects more than 3 million in the UK and causes bone to become fragile and susceptible to fracture and breakage.

Sugar chains coat all cells in the body and function in a variety ways, such as supporting the immune system and defining blood groups, but their structure has a 'randomness' that has made them a very complex feature to understand.

A researcher in bone formation and a researcher in cell sugars combined expertise to examine whether these sugars might have a role to play in forming bone. They treated cells with a commonly used laboratory chemical that alters sugar chains, called kifunensine, to see how they would react.

Dr Daniel Ungar, from the University's Department of Biology, said: "The chemical, kifunensine, is well known to alter the structure of sugar chains. It has been examined for potential drug treatments before, but is yet to make any clinical trials. We wanted to see what it might do to bone-forming stem cells in laboratory testing.

"The complexity of these sugars means that they have never been tested in this way before, but we found that after a couple of days, interrupting the sugars' normal function enabled them to enhance bone formation processes in stem cells."

This is the first time that these sugar chains have been connected to bone growth and could pave the way for new investigations into possible future treatments for osteoporosis, where bone strength is a particular issue. Professor Paul Genever, from the University of York's Department of Biology, said: "Currently the most commonly used drugs for treating osteoporosis aim to prevent further bone loss to halt progression of the disease, but we have no reliable candidates for actually restoring bone strength.

"This is an exciting step forward into understanding the role of these sugars in its relationship to bone growth, but we still have some way to go in realising just how this mechanism works and what would happen to the cells when treated inside the body."

The team are now working to investigate whether the chemical treatment can be targeted to stem cells involved with bone growth to ensure that it has no adverse reactions on other cells in the body.

They are also doing further testing to understand why inhibiting the sugar chains has an impact on the way stem cells stimulate bone formation.

The research, supported by Arthritis Research UK and funded by EPSRC, is published in the Journal of Cell Science.

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Story Source:

Materials provided by University of York. Note: Content may be edited for style and length.

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Journal Reference:

1. Katherine M. Wilson, Alistair M. Jagger, Matthew Walker, Estere Seinkmane, James M. Fox, Roland Kröger, Paul Genever, Daniel Ungar. Glycans modify mesenchymal stem cell differentiation to impact the function of resulting osteoblasts. Journal of Cell Science, 2018; DOI: 10.1242/jcs.209452

Diet may influence the spread of a deadly type of breast cancer, study finds

A single protein building block commonly found in food may hold a key to preventing the spread of an often-deadly type of breast cancer, according to a new multicenter study published today in the medical journal Nature.

Investigators found that by limiting an amino acid called asparagine in laboratory mice with triple-negative breast cancer, they could dramatically reduce the ability of the cancer to travel to distant sites in the body. Among other techniques, the team used dietary restrictions to limit asparagine.

Foods rich in asparagine include dairy, whey, beef, poultry, eggs, fish, seafood, asparagus, potatoes, legumes, nuts, seeds, soy and whole grains. Foods low in asparagine include most fruits and vegetables.

"Our study adds to a growing body of evidence that suggests diet can influence the course of the disease," said Simon Knott, PhD, associate director of the Center for Bioinformatics and Functional Genomics at Cedars-Sinai and one of two first authors of the study. The research was conducted at more than a dozen institutions.

If further research confirms the findings in human cells, limiting the amount of asparagine cancer patients ingest could be a potential strategy to augment existing therapies and to prevent the spread of breast cancer, Knott added.

The researchers studied triple-negative breast cancer cells, which grow and spread faster than most other types of cancer cells. It is called triple negative because it lacks receptors for the hormones estrogen and progesterone and makes little of a protein called HER2. As a result, it resists common treatments -- which target these factors and has a higher-than-average mortality rate.

Research from past studies found that most tumor cells remain in the primary breast site, but a subset of cells leaves the breast and enters the bloodstream. Those cells colonize in the lungs, brain and liver, where they proliferate. The study team wanted to understand the particular traits of the tumor cells circulating in the blood and in the sites where the cancer has spread.

The researchers discovered that the appearance of asparagine synthetase -- the enzyme cells used to make asparagine -- in a primary tumor was strongly associated with later cancer spread.

The researchers also found that metastasis was greatly limited by reducing asparagine synthetase, treatment with the chemotherapy drug L-asparaginase, or dietary restriction. When the lab mice were given food rich in asparagine, the cancer cells spread more rapidly.

"The study results are extremely suggestive that changes in diet might impact both how an individual responds to primary therapy and their chances of lethal disease spreading later in life," said the study's senior author, Gregory J. Hannon, PhD, professor of Cancer Molecular Biology and director, Cancer Research UK Cambridge Institute, University of Cambridge in England.

Investigators now are considering conducting an early-phase clinical trial in which healthy participants would consume a low-asparagine diet. If the diet results in decreased levels of asparagine, the next scientific step would involve a clinical trial with cancer patients. That trial likely would employ dietary restrictions as well as chemotherapy and immunotherapy, Knott said.

Studying the effects of asparagine also could alter treatments for other types of cancer, investigators say.

"This study may have implications not only for breast cancer, but for many metastatic cancers," said Ravi Thadhani, MD, MPH, vice dean, Research and Graduate Research Education, at Cedars-Sinai.

Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health, under these awards numbers: P50-CA58223-09A1, R00 CA194077 and 5P30CA045508; by the National Institutes of Health grant number 5 P01 CA013106-44; and by the Susan G. Komen Foundation (SAC110006); the ICR and CRUK grand challenge award (C59824/A25044); and a grant from the DOD BCRP (W81XWH-1-0300).

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Story Source:

Materials provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.

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Journal Reference:

1. Simon R. V. Knott, Elvin Wagenblast, Showkhin Khan, Sun Y. Kim, Mar Soto, Michel Wagner, Marc-Olivier Turgeon, Lisa Fish, Nicolas Erard, Annika L. Gable, Ashley R. Maceli, Steffen Dickopf, Evangelia K. Papachristou, Clive S. D’Santos, Lisa A. Carey, John E. Wilkinson, J. Chuck Harrell, Charles M. Perou, Hani Goodarzi, George Poulogiannis, Gregory J. Hannon. Asparagine bioavailability governs metastasis in a model of breast cancer. Nature, 2018; DOI: 10.1038/nature25465

Poor fitness linked to weaker brain fiber, higher dementia risk

Scientists have more evidence that exercise improves brain health and could be a lifesaving ingredient that prevents Alzheimer's disease.

In particular, a new study from UT Southwestern's O'Donnell Brain Institute suggests that the lower the fitness level, the faster the deterioration of vital nerve fibers in the brain. This deterioration results in cognitive decline, including memory issues characteristic of dementia patients.

"This research supports the hypothesis that improving people's fitness may improve their brain health and slow down the aging process," said Dr. Kan Ding, a neurologist from the Peter O'Donnell Jr. Brain Institute who authored the study.

White matter

The study published in the Journal of Alzheimer's Disease focused on a type of brain tissue called white matter, which is composed of millions of bundles of nerve fibers used by neurons to communicate across the brain.

Dr. Ding's team enrolled older patients at high risk to develop Alzheimer's disease who have early signs of memory loss, or mild cognitive impairment (MCI). The researchers determined that lower fitness levels were associated with weaker white matter, which in turn correlated with lower brain function.

Distinctive tactics

Unlike previous studies that relied on study participants to assess their own fitness, the new research objectively measured cardiorespiratory fitness with a scientific formula called maximal oxygen uptake. Scientists also used brain imaging to measure the functionality of each patient's white matter.

Patients were then given memory and other cognitive tests to measure brain function, allowing scientists to establish strong correlations between exercise, brain health, and cognition.

Lingering mysteries

The study adds to a growing body of evidence pointing to a simple yet crucial mandate for human health: Exercise regularly.

However, the study leaves plenty of unanswered questions about how fitness and Alzheimer's disease are intertwined. For instance, what fitness level is needed to notably reduce the risk of dementia? Is it too late to intervene when patients begin showing symptoms?

Some of these topics are already being researched through a five-year national clinical trial led by the O'Donnell Brain Institute.

The trial, which includes six medical centers across the country, aims to determine whether regular aerobic exercise and taking specific medications to reduce high blood pressure and cholesterol levels can help preserve brain function. It involves more than 600 older adults at high risk to develop Alzheimer's disease.

"Evidence suggests that what is bad for your heart is bad for your brain. We need studies like this to find out how the two are intertwined and hopefully find the right formula to help prevent Alzheimer's disease," said Dr. Rong Zhang of UT Southwestern, who oversees the clinical trial and is Director of the Cerebrovascular Laboratory in the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, where the Dallas arm of the study is being carried out.

Prior findings

The research builds upon prior investigations linking healthy lifestyles to better brain function, including a 2013 study from Dr. Zhang's team that found neuronal messages are more efficiently relayed in the brains of older adults who exercise.

In addition, other teams at the O'Donnell Brain Institute are designing tests for the early detection of patients who will develop dementia, and seeking methods to slow or stop the spread of toxic proteins associated with the disease such as beta-amyloid and tau, which are blamed for destroying certain groups of neurons in the brain.

"A lot of work remains to better understand and treat dementia," said Dr. Ding, Assistant Professor of Neurology & Neurotherapeutics. "But, eventually, the hope is that our studies will convince people to exercise more."

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Story Source:

Materials provided by UT Southwestern Medical Center. Note: Content may be edited for style and length.

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Journal Reference:

1. Kan Ding, Takashi Tarumi, David C. Zhu, Benjamin Y. Tseng, Binu P. Thomas, Marcel Turner, Justin Repshas, Diana R. Kerwin, Kyle B. Womack, Hanzhang Lu, C. Munro Cullum, Rong Zhang. Cardiorespiratory Fitness and White Matter Neuronal Fiber Integrity in Mild Cognitive Impairment. Journal of Alzheimer's Disease, 2017; 61 (2): 729 DOI: 10.3233/JAD-170415

Cognitive decline: Is low blood sodium a risk factor?

Low sodium levels in the blood have been linked to declines in cognitive function among otherwise healthy older men in a new study, which has now been published in the Clinical Journal of the American Society of Nephrology.

Scientists have linked low blood sodium levels to cognitive impairment in older men.

The authors suggest that addressing these low sodium levels — which are known medically as hyponatremia — could be valuable in halting cognitive decline as people age.

Hyponatremia occurs when blood sodium levels fall below 135 millimoles per liter (mmol/L).

Studies have shown that low sodium levels may be tied to an increased risk of attention deficits, falls, fractures, heart problems, and premature death.

Medical News Today have previously reported the results of studies warning of the dangers of drinking too much fluid when exercising, as this can lead to exercise-associated hyponatremia (EAH).

Mild symptoms of EAH include dizziness, nausea, and puffiness, but more severe cases can be fatal. It is estimated that at least 14 athletes have died from EAH.

The authors of the new study, from the University of Colorado Anschutz Medical Campus in Aurora, set out to investigate.Severe cases of hyponatremia have previously been associated with neurological and cognitive problems, but studies have not pinpointed how different levels of sodium in the blood affect cognition in older adults.

Risk of cognitive decline increased

The researchers behind the new study looked at data from 5,435 healthy men aged 65 and older, who were each followed for an average of 4.6 years.

The results show that men whose sodium levels were 126–140 mmol/L were 30 percent more likely to have symptoms of cognitive impairment at the start of the study and 37 percent more likely to experience symptoms of cognitive decline over time, compared with men with sodium levels of 141–142 mmol/L.

Interestingly, high sodium levels of 143–153 mmol/L were also associated with cognitive decline over time.

Lead study author Kristen Nowak, Ph.D., says that more studies are needed to further investigate what corrective action can be taken to prevent cognitive decline in people with hyponatremia.

She adds, "Slightly lower sodium levels in the blood are likely to be unnoticed in clinical practice."

"Because both slightly lower serum sodium levels and mild changes in cognitive function are common occurrences with advancing age, future research on this topic is important — including determining whether correcting lower sodium levels affects cognitive function."