Combatting Memory Decline Among Menopausal Women Could Be the Next Research Frontier for Hypnotic Relaxation Therapy

Memory decline — a frequent complaint of menopausal women — potentially could be lessened by hypnotic relaxation therapy, say Baylor University researchers, who already have done studies showing that such therapy eases hot flashes, improves sleep and reduces stress in menopausal women.

Their review — “Memory Decline in Peri- and Post-menopausal Women: The Potential of Mind-Body Medicine to Improve Cognitive Performance” — is published in the journal Integrative Medicine Insights. October has been designated World Menopause Month by the International Menopause Society.

Initial research by Baylor, funded by the National Institutes of Health, focused on hot flashes, finding that hypnotic relaxation therapy lessened them, but “along the way, we discovered there are a lot of secondary benefits, including significantly improved sleep and mood,” said Jim R. Sliwinski, a doctoral student in the department of psychology and neuroscience in Baylor’s College of Arts & Sciences.

Co-researcher Gary Elkins, Ph.D., theorizes that sleep, mood and hot flashes associated with decreased estrogen also have a bearing on memory. Their publication, which reviews previous research by other scholars, proposes a framework for how mind-body interventions may improve memory, which could prove fruitful in doing future research.

“Memory decline may not be solely about decreased estrogen,” said Elkins, director of Baylor’s Mind-Body Medicine Research Laboratory and a professor of psychology and neuroscience.

Peri- and post-menopausal women may find mind-body therapies attractive for many reasons, among them that they do not have the side effects of medications or hormone therapy, said Elkins, author of “Relief from Hot Flashes: The Natural, Drug-Free Program to Reduce Hot Flashes, Improve Sleep and Ease Stress.”

While hormone therapy can increase estrogen, it also is associated with an increased risk of breast cancer and cardiovascular disease for some women, he said.

Researchers have noted that while memory decline can occur with aging in both men and women, women are more likely to report a greater number of memory problems, associating it with estrogen decline. Women also report more concerns about memory than pre-menopausal women do, according to several large-scale survey studies.

A factor that may impact memory is that women are dealing with increased responsibilities, stress or depression over such issues as caring for aging parents. In addition, their concern about memory problems may cause them to be more aware of memory lapses, Sliwinski said.

Even women who can safely be treated with estrogen do not necessarily have improved memory. “It sometimes even is associated with cognition problems,” he said.

Although there are questions about sleep’s specific role in forming and storing memories, researchers generally agree that consolidated sleep throughout a whole night is optimal for learning and memory.

Memory tests and scores over time with study participants — both pre-and post-menopausal — could help shed light on how menopause affects recollection, the Baylor researchers said.

(Image: Shutterstock)

Blood Vessels in the Eye Linked With IQ, Cognitive Function

The width of blood vessels in the retina, located at the back of the eye, may indicate brain health years before the onset of dementia and other deficits, according to a new study published in Psychological Science, a journal of the Association for Psychological Science.

Research shows that younger people who score low on intelligence tests, such as IQ, tend to be at higher risk for poorer health and shorter lifespan, but factors like socioeconomic status and health behaviors don’t fully account for the relationship. Psychological scientist Idan Shalev of Duke University and colleagues wondered whether intelligence might serve as a marker indicating the health of the brain, and specifically the health of the system of blood vessels that provides oxygen and nutrients to the brain.

To investigate the potential link between intelligence and brain health, the researchers borrowed a technology from a somewhat unexpected domain: ophthalmology.

Shalev and colleagues used digital retinal imaging, a relatively new and noninvasive method, to gain a window onto vascular conditions in the brain by looking at the small blood vessels of the retina, located at the back of the eye. Retinal blood vessels share similar size, structure, and function with blood vessels in the brain and can provide a way of examining brain health in living humans.

The researchers examined data from participants taking part in the Dunedin Multidisciplinary Health and Development Study, a longitudinal investigation of health and behavior in over 1000 people born between April 1972 and March 1973 in Dunedin, New Zealand.

The results were intriguing.

Having wider retinal venules was linked with lower IQ scores at age 38, even after the researchers accounted for various health, lifestyle, and environmental risk factors that might have played a role.

Individuals who had wider retinal venules showed evidence of general cognitive deficits, with lower scores on numerous measures of neurospsychological functioning, including verbal comprehension, perceptual reasoning, working memory, and executive function.

Surprisingly, the data revealed that people who had wider venules at age 38 also had lower IQ in childhood, a full 25 years earlier.

It’s “remarkable that venular caliber in the eye is related, however modestly, to mental test scores of individuals in their 30s, and even to IQ scores in childhood,” the researchers observe.

The findings suggest that the processes linking vascular health and cognitive functioning begin much earlier than previously assumed, years before the onset of dementia and other age-related declines in brain functioning.

“Digital retinal imaging is a tool that is being used today mainly by eye doctors to study diseases of the eye,” Shalev notes. “But our initial findings indicate that it may be a useful investigative tool for psychological scientists who want to study the link between intelligence and health across the lifespan.”

The current study doesn’t address the specific mechanisms that drive the relationship between retinal vessels and cognitive functioning, but the researchers surmise that it may have to do with oxygen supply to the brain.

“Increasing knowledge about retinal vessels may enable scientists to develop better diagnosis and treatments to increase the levels of oxygen into the brain and by that, to prevent age-related worsening of cognitive abilities,” they conclude.

Homer prevents stress-induced cognitive deficits

Before examinations and in critical situations, we need to be particularly receptive and capable of learning. However, acute exam stress and stage fright causes learning blockades and reduced memory function. Scientists from the Max Planck Institute of Psychiatry in Munich have now discovered a mechanism responsible for these cognitive deficits, which functions independently of stress hormones. In animal studies, the researchers show that social stress reduces the volume of Homer-1 in the hippocampus – a region of the brain that plays a central role in learning. This specific protein deficiency leads to altered neuronal activity followed by deterioration in the animals’ learning performance. In the experiments, it was possible to prevent the cognitive deficit by administering additional volumes of the protein to the mice. This suggests that Homer-1 could provide a key molecule for the development of drugs for the treatment of stress-induced cognitive deficits.

Klaus Wagner, a scientist at the Max Planck Institute of Psychiatry, studied the learning behaviour of mice that had been subjected to severe stress. He exposed the animals to social stress – a pressure also frequently experienced by humans today. A male mouse was placed in the cage of an aggressive member of the same species for five minutes. The latter tried to banish the “intruder” by attacking it. Unlike in nature, the test mouse was unable to flee from the cage and was under severe stress, as substantiated by measurements of the stress hormones in its blood.

Following a period of eight hours in which the animal was able to recover in its own cage, its behaviour was examined. While the mouse’s motivation, activity and sensory functions were not impaired at this time, it displayed clear deficits in its learning behaviour. A single five-minute situation of social stress was sufficient, therefore, to impair the animal’s learning performance hours later.

The researchers at the Max Planck Institute then tried to establish which mechanisms were responsible for these cognitive deficits. They identified the protein Homer-1, the concentration of which declines specifically in the hippocampus after exposure to stress. Through its interaction with the neuronal messenger substance glutamate and its receptors, Homer-1 modulates the communication in the neuronal synapses. When the volume of Homer-1 in the hippocampus falls after exposure to stress, the natural receptor activity is severely disrupted and learning capacity declines. The researchers were able to prevent this effect by increasing the Homer-1 concentration again.

Mathias Schmidt, Research Group Leader at the Max Planck Institute of Psychiatry interprets the results as follows: “With our study, we demonstrated the regulation of glutamate-mediated communication in the hippocampus, which directly controls learning behaviour. This mechanism functions independently of stress hormones for the most part. The molecule Homer-1 assumes a key role in this process and will hopefully provide new possibilities in future for targeted pharmaceutical intervention for the avoidance of cognitive deficits.”

Linking insulin to learning: Important insights in research with worms

Recent work by Harvard researchers demonstrates how the signaling pathway of insulin and insulinlike peptides plays a critical role in helping to regulate learning and memory.

The research, led by Yun Zhang, associate professor of organismic and evolutionary biology, is described in a Feb. 6 paper in Neuron.

“People think of insulin and diabetes, but many metabolic syndromes are associated with some types of cognitive defects and behavioral disorders, like depression or dementia,” Zhang said. “That suggests that insulin and insulinlike peptides may play an important role in neural function, but it’s been very difficult to nail down the underlying mechanism, because these peptides do not have to function through synapses that connect different neurons in the brain.”

To get at that mechanism, Zhang and colleagues turned to an organism whose genome and nervous system are well described and highly accessible by genetics: C. elegans.

Using genetic tools, researchers altered the transparent worms by removing their ability to create individual insulinlike compounds. These new “mutant” worms were then tested to see whether they would learn to avoid eating a particular type of bacteria that is known to infect the worms. Tests showed that although some worms did learn to steer clear of the bacteria, others didn’t — suggesting that removing a specific insulinlike compound halted the worms’ ability to learn.

Researchers were surprised to find, however, that it wasn’t just removing the molecules that could make the animals lose the ability to learn — some peptides were found to inhibit learning.

“We hadn’t predicted that we would find both positive and negative regulators from these peptides,” Zhang said. “Why does the animal need this bidirectional regulation of learning? One possibility is that learning depends on context. There are certain things you want to learn — for example, the worms in these experiments wanted to learn that they shouldn’t eat this type of infectious bacteria. That’s a positive regulation of the learning. But if they needed to eat, even if it is a bad food, to survive, they would need a way to suppress this type of learning.”

Even more surprising for Zhang and her colleagues was evidence that the various insulinlike molecules could regulate each other.

“Many animals, including humans, have multiple insulinlike molecules, and it appears that these molecules can act like a network,” she said. “Each of them may play a slightly different role in the nervous system, and they function together to coordinate the signaling related to learning and memory. By changing the way the molecules interact, the brain can fine-tune learning in a host of different ways.”

Human cognition depends upon slow-firing neurons

Good mental health and clear thinking depend upon our ability to store and manipulate thoughts on a sort of “mental sketch pad.” In a new study, Yale School of Medicine researchers describe the molecular basis of this ability — the hallmark of human cognition — and describe how a breakdown of the system contributes to diseases such as schizophrenia and Alzheimer’s disease.

“Insults to these highly evolved cortical circuits impair the ability to create and maintain our mental representations of the world, which is the basis of higher cognition,” said Amy Arnsten, professor of neurobiology and senior author of the paper published in the Feb. 20 issue of the journal Neuron.

High-order thinking depends upon our ability to generate mental representations in our brains without any sensory stimulation from the environment. These cognitive abilities arise from highly evolved circuits in the prefrontal cortex. Mathematical models by former Yale neurobiologist Xiao-Jing Wang, now of New York University, predicted that in order to maintain these visual representations the prefrontal cortex must rely on a family of receptors that allow for slow, steady firing of neurons. The Yale scientists show that NMDA-NR2B receptors involved in glutamate signaling regulate this neuronal firing.  These receptors, studied at Yale for more than a decade, are responsible for activity of highly evolved brain circuits found especially in primates.

Earlier studies have shown these types of NMDA receptors are often altered in patients with schizophrenia. The Neuron study suggests that those suffering from the disease may be unable to hold onto a stable view of the world. Also, these receptors seem to be altered in Alzheimer’s patients, which may contribute to the cognitive deficits of dementia.

The lab of Dr. John Krystal, chair of the department of psychiatry at Yale, has found that the anesthetic ketamine, abused as a street drug, blocks NMDA receptors and can mimic some of the symptoms of schizophrenia. The current study in Neuron shows that ketamine may reduce the firing of the same higher-order neural circuits that are decimated in schizophrenia. 

“Identifying the receptor needed for higher cognition may help us to understand why certain genetic insults lead to cognitive impairment and will help us to develop strategies for treating these debilitating disorders,” Arnsten said.

Momentum builds in quest to find cure for childhood brain disease

Rasmussen Encephalitis strikes healthy kids; only known treatment removing half the brain.

How do you find a cure for a devastating pediatric brain disease so rare that it can take decades to build a meaningful research base?

In 2010, the parents of a patient created the Rasmussen Encephalitis (RE) Children’s Project to help solve this problem. In a short amount of time, the foundation has raised funds to establish a consortium of top researchers, build a collection of samples of the disease from around the world and support projects to study the disease tissue and search for genetic links. The goal is to find a cure.

Researchers at the David Geffen School of Medicine at UCLA have played a vital role in the ongoing research, and the foundation recently provided a second round of funding to continue their work. The gift of $125,000 builds on the organization’s donation of $111,000 made in 2011. 

"We are still in the early stages of research, but our momentum is building," said Seth H. Wohlberg, founder of the RE Children’s Project, and father of Grace, 15, who was stricken by the disease when she was 10 years old. "One of our key accomplishments has been to create an international system so that we can coordinate and transfer RE brain tissue and DNA material from the patients and parents. Collecting these samples is vital to advancing the research."

With the additional funding, UCLA researchers will apply cutting-edge DNA sequencing technology to determine whether a virus, or some other infectious agent, causes RE. They also plan to develop an animal model of the disease using cells obtained from the RE samples. 

The researchers include Dr. Gary Mathern, professor of pediatric neurosurgery and director of the UCLA Pediatric Epilepsy Program at Mattel Children’s Hospital; Carol Kruse, professor of neurosurgery; and Geoffrey Owens, visiting assistant researcher in neurosurgery.

"I am grateful to collaborate with a devoted father who has taken on the enormous task of advancing research for RE," said Mathern. "Thanks to his leadership, we now have the network to collect the tissue and DNA needed to study the brain, immunologic cells and genetics to unlock what causes this disease and develop new treatments or a cure. The RE Children’s Project has truly helped accelerate our research, bringing new information and resources that could have taken 10 more years to develop to the forefront today."

Rasmussen Encephalitis is a neurological disease that causes intractable seizures, cognitive deficits and paralysis of half of the body.  It is very rare and only a few hundred cases have been reported worldwide. RE typically affects previously normal children between the ages of two and ten years old. The disease process can run its course over a one to two year period during which time one half of the body is rendered useless and epileptic seizures continue unabated. 

An unusual feature of the disease is that it is usually confined to one hemisphere of the brain and is resistant to standard anti-seizure medicines. Currently the only known “cure” is radical- the surgical removal or disconnection of the affected side of the brain known as a hemispherectomy.

In the summer of 2008, the Wohlberg’s 10-year-old daughter Grace started to experience epileptic seizures. After months of testing, her parents learned that she had the extremely rare neurological disorder. Grace underwent an initial hemispherectomy surgery in February 2009. However, her seizures recurred so her parents then brought Grace to UCLA to complete the hemispherectomy which was performed by Mathern in March 2010. 

Today, Grace attends high school with the assistance of a full-time aide. While the surgery has stopped the seizures, Grace faces lifelong disabilities including partial blindness, cognitive issues and learning how to walk again. She is also active in helping her father promote the RE Children’s Project.

"It’s really supportive to let people know our story," said Grace. "Every year, my dad does a fundraiser and a lot of people come out to support it. It’s fun to be there and see all the people who care and want to help."

(Image: Wikimedia Commons)

Long-Term Anabolic-Androgenic Steroid Use May Severely Impact Visuospatial Memory

The long-term use of anabolic-androgenic steroids (AAS) may severely impact the user’s ability to accurately recall the shapes and spatial relationships of objects, according to a recent study conducted by McLean Hospital and Harvard Medical School investigators.

In the study, published online in the journal Drug and Alcohol Dependence, McLean Hospital Research Psychiatrist Harrison Pope, MD, used a variety of tests to determine whether AAS users developed cognitive defects due to their admitted history of abuse.

"Our work clearly shows that while some areas of brain function appear to be unaffected by the use of AAS, users performed significantly worse on the visuospatial tests that were administered. Those deficits directly corresponded to their length of use of anabolic-androgenic steroids," explained Pope. "Impaired visuospatial memory means that a person might have difficulty, for example, in remembering how to find a location, such as an address on a street or a room in a building… We are worried that with higher doses of AAS and longer periods of lifetime exposure, some people might even eventually develop visuospatial deficits similar to those sometimes seen in elderly people with dementia, who can easily become lost or disoriented."