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A Good Memory or a Bad One? One Brain Molecule Decides.

Yasemin Saplakoglu wrote . . . . . . . . .

You’re on the vacation of a lifetime in Kenya, traversing the savanna on safari, with the tour guide pointing out elephants to your right and lions to your left. Years later, you walk into a florist’s shop in your hometown and smell something like the flowers on the jackalberry trees that dotted the landscape. When you close your eyes, the store disappears and you’re back in the Land Rover. Inhaling deeply, you smile at the happy memory.

Now let’s rewind. You’re on the vacation of a lifetime in Kenya, traversing the savanna on safari, with the tour guide pointing out elephants to your right and lions to your left. From the corner of your eye, you notice a rhino trailing the vehicle. Suddenly, it sprints toward you, and the tour guide is yelling to the driver to hit the gas. With your adrenaline spiking, you think, “This is how I am going to die.” Years later, when you walk into a florist’s shop, the sweet floral scent makes you shudder.

“Your brain is essentially associating the smell with positive or negative” feelings, said Hao Li, a postdoctoral researcher at the Salk Institute for Biological Studies in California. Those feelings aren’t just linked to the memory; they are part of it: The brain assigns an emotional “valence” to information as it encodes it, locking in experiences as good or bad memories.

And now we know how the brain does it. As Li and his team reported recently in Nature, the difference between memories that conjure up a smile and those that elicit a shudder is established by a small peptide molecule known as neurotensin. They found that as the brain judges new experiences in the moment, neurons adjust their release of neurotensin, and that shift sends the incoming information down different neural pathways to be encoded as either positive or negative memories.

The discovery suggests that in its creation of memories, the brain may be biased toward remembering things fearfully — an evolutionary quirk that may have helped to keep our ancestors cautious.

The findings “give us significant insights into how we deal with conflicting emotions,” said Tomás Ryan, a neuroscientist at Trinity College Dublin who was not involved in the study. It “has really challenged my own thinking in how far we can push a molecular understanding of brain circuitry.”

It also opens opportunities to probe the biological underpinnings of anxiety, addiction and other neuropsychiatric conditions that may sometimes arise when breakdowns in the mechanism lead to “too much negative processing,” Li said. In theory, targeting the mechanism through novel drugs could be an avenue to treatment.

“This is really an extraordinary study” that will have a profound impact on psychiatric concepts about fear and anxiety, said Wen Li, an associate professor at Florida State University who studies the biology of anxiety disorders and was not involved in the study.

Dangerous Berries

Neuroscientists are still far from understanding exactly how our brains encode and remember memories — or forget them, for that matter. Valence assignment is nonetheless seen as an essential part of the process for forming emotionally charged memories.

The ability of the brain to record environmental cues and experiences as good or bad memories is critical for survival. If eating a berry makes us very sick, we instinctively avoid that berry and anything that looks like it thereafter. If eating a berry brings delicious satisfaction, we may seek out more. “To be able to question whether to approach or to avoid a stimulus or an object, you have to know whether the thing is good or bad,” Hao Li said.

Profile photo of researchers Kay Tye and Hao Li of the Salk Institute for Biological Studies smiling and standing back-to-back.

Memories that link disparate ideas — like “berry” and “sickness” or “enjoyment” — are called associative memories, and they are often emotionally charged. They form in a tiny almond-shaped region of the brain called the amygdala. Though traditionally known as the brain’s “fear center,” the amygdala responds to pleasure and other emotions as well.

One part of the amygdala, the basolateral complex, associates stimuli in the environment with positive or negative outcomes. But it was not clear how it does that until a few years ago, when a group at the Massachusetts Institute of Technology led by the neuroscientist Kay Tye discovered something remarkable happening in the basolateral amygdala of mice, which they reported in Nature in 2015 and in Neuron in 2016.

Tye and her team peered into the basolateral amygdala of mice learning to associate a sound with either sugar water or a mild electric shock and found that, in each case, connections to a different group of neurons strengthened. When the researchers later played the sound for the mice, the neurons that had been strengthened by the learned reward or punishment became more active, demonstrating their involvement in the associated memory.

But Tye’s team couldn’t tell what was steering the information toward the right group of neurons. What acted as the switch operator?

Dopamine, a neurotransmitter known to be important in reward and punishment learning, was the obvious answer. But a 2019 study showed that although this “feel-good” molecule could encode emotion in memories, it couldn’t assign the emotion a positive or negative value.

So the team began looking at the genes expressed in the two areas where positive and negative memories were forming, and the results turned their attention to neuropeptides, small multifunctional proteins that can slowly and steadily strengthen synaptic connections between neurons. They found that one set of amygdala neurons had more receptors for neurotensin than the other.

This finding was encouraging because earlier work had shown that neurotensin, a meager molecule just 13 amino acids long, is involved in the processing of reward and punishment, including the fear response. Tye’s team set out to learn what would happen if they changed the amount of neurotensin in the brains of mice.

Tiny Molecule With a Big Personality

What followed were years of surgically and genetically manipulating mouse neurons and recording the behaviors that resulted. “By the time I finished my Ph.D., I had done at least 1,000 surgeries,” said Praneeth Namburi, an author on both of the papers and the leader of the 2015 one.

During that time, Tye moved her growing lab across the country from MIT to the Salk Institute. Namburi stayed at MIT — he now studies how dancers and athletes represent emotions in their movements — and Hao Li joined Tye’s lab as a postdoc, picking up Namburi’s notes. The project was stalled further by the pandemic, but Hao Li kept it going by requesting essential-personnel status and basically moving into the lab, sometimes even sleeping there. “I don’t know how he stayed so motivated,” Tye said.

The researchers knew that the neurons in the amygdala did not make neurotensin, so they first had to figure out where the peptide was coming from. When they scanned the brain, they found neurons in the thalamus that produced a lot of neurotensin and poked their long axons into the amygdala.

Tye’s team then taught mice to associate a tone with either a treat or a shock. They found that neurotensin levels increased in the amygdala after reward learning and dropped after punishment learning. By genetically altering the mice’s thalamic neurons, they were able to control how and when the neurons released neurotensin. Activating the neurons that released neurotensin into the amygdala promoted reward learning, while knocking out the neurotensin genes strengthened punishment learning.

They also discovered that the assignment of valences to environmental cues promotes active behavioral responses to them. When the researchers prevented the amygdala from receiving information about positive or negative valence by knocking out the thalamic neurons, the mice were slower to collect rewards; in threatening situations, the mice froze rather than running away.

So what do these results suggest would happen if your valence-assignment system broke down — while an angry rhino was charging you, for example? “You would just only slightly care,” Tye said. Your indifference in the moment would be recorded in the memory. And if you found yourself in a similar situation later in life, your memory would not inspire you to try urgently to escape, she added.

However, the likelihood that an entire brain circuit would shut down is low, said Jeffrey Tasker, a professor in the brain institute at Tulane University. It’s more probable that mutations or other problems would simply prevent the mechanism from working well, instead of reversing the valence. “I would be hard-pressed to see a situation where somebody would mistake a charging tiger as a love approach,” he said.

Hao Li agreed and noted that the brain likely has fallback mechanisms that would kick in to reinforce rewards and punishments even if the primary valence system failed. This would be an interesting question to pursue in future work, he added.

One way to study defects in the valence system, Tasker noted, might be to examine the very rare people who don’t report feeling fear, even in situations routinely judged as terrifying. Various uncommon conditions and injuries can have this effect, such as Urbach-Wiethe syndrome, which can cause calcium deposits to form in the amygdala, dampening the fear response.

The Brain Is a Pessimist

The findings are “pretty big in terms of advancing our understanding and thinking of the fear circuit and the role of the amygdala,” Wen Li said. We are learning more about chemicals like neurotensin that are less well known than dopamine but play critical roles in the brain, she added.

The work points toward the possibility that the brain is pessimistic by default, Hao Li said. The brain has to make and release neurotensin to learn about rewards; learning about punishments takes less work.

Further evidence of this bias comes from the reaction of the mice when they were first put into learning situations. Before they knew whether the new associations would be positive or negative, the release of neurotensin from their thalamic neurons decreased. The researchers speculate that new stimuli are assigned a more negative valence automatically until their context is more certain and can redeem them.

“You’re more responsive to negative experiences versus positive experiences,” Hao Li said. If you almost get hit by a car, you’ll probably remember that for a very long time, but if you eat something delicious, that memory is likely to fade in a few days.

Ryan is more wary of extending such interpretations to humans. “We’re dealing with laboratory mice who are brought up in very, very impoverished environments and have very particular genetic backgrounds,” he said.

Still, he said, it would be interesting to determine in future experiments whether fear is the actual default state of the human brain — and if that varies for different species, or even for individuals with different life experiences and stress levels.

The findings are also a great example of how integrated the brain is, Wen Li said: The amygdala needs the thalamus, and the thalamus likely needs signals from elsewhere. It would be interesting to know which neurons in the brain are feeding signals to the thalamus, she said.

A recent study published in Nature Communications found that a single fear memory can be encoded in more than one region of the brain. Which circuits are involved probably depends on the memory. For example, neurotensin is probably less crucial for encoding memories that don’t have much emotion attached to them, such as the “declarative” memories that form when you learn vocabulary.

For Tasker, the clear-cut relationship that Tye’s study found between a single molecule, a function and a behavior was very impressive. “It’s rare to find a one-to-one relationship between a signal and a behavior, or a circuit and a function,” Tasker said.

Neuropsychiatric Targets

The crispness of the roles of neurotensin and the thalamic neurons in assigning valence might make them ideal targets for drugs aimed at treating neuropsychiatric disorders. In theory, if you can fix the valence assignment, you might be able to treat the disease, Hao Li said.

It’s not clear whether therapeutic drugs targeting neurotensin could change the valence of an already formed memory. But that’s the hope, Namburi said.

Pharmacologically, this won’t be easy. “Peptides are notoriously difficult to work with,” Tasker said, because they don’t cross the blood-brain barrier that insulates the brain against foreign materials and fluctuations in blood chemistry. But it’s not impossible, and developing targeted drugs is very much where the field is headed, he said.

Our understanding of how the brain assigns valence still has important gaps. It’s not clear, for example, which receptors the neurotensin is binding to in amygdala neurons to flip the valence switch. “That will bother me until it is filled,” Tye said.

Too much is also still unknown about how problematic valence assignments may drive anxiety, addiction or depression, said Hao Li, who was recently appointed as an assistant professor at Northwestern University and is planning to explore some of these questions further in his new lab. Beyond neurotensin, there are many other neuropeptides in the brain that are potential targets for interventions, Hao Li said. We just don’t know what they all do. He’s also curious to know how the brain would react to a more ambiguous situation in which it wasn’t clear whether the experience was good or bad.

These questions linger in Hao Li’s brain long after he packs up and goes home for the night. Now that he knows which network of chatty cells in his brain drives the emotions he feels, he jokes with friends about his brain pumping out neurotensin or holding it back in response to every bit of good or bad news.

“It’s clear that this is biology, it happens to everyone,” he said. That “makes me feel better when I’m in a bad mood.”


Source : Quanta Magazine

Music: Bridging Memories for People With Alzheimer’s

Dennis Thompson wrote . . . . . . . . .

Wes Mika started out on drums, but in his heart he was a tambourine man.

“He got fascinated by the little silver discs on the tambourine,” said his wife, Susan Mika. “Sometimes he would hit the tambourine with the little mallets of the drum. He just he loved that tambourine.”

Wes, 77, has dementia and lives in a memory care facility in Arlington Heights, Ill., a northwest suburb of Chicago. He and Susan, 76, participated in a music program designed to help dementia patients connect with their loved ones.

The program, Musical Bridges to Memory, has been shown to enhance patients’ ability to non-verbally interact with their caregivers, according to a study published recently in the journal Alzheimer Disease and Associated Disorders.

The music therapy also reduces troubling dementia symptoms like agitation, anxiety and depression.

“He’s in a wheelchair, and it was just a nice, close connection for both of us,” Susan said. “We both enjoyed it. I would sing the lyrics I knew, and at times I would see him moving his lips. He doesn’t speak loudly but he would move his lips, so I think he knew the words and was connected with the music.”

The music program was developed by the non-profit Institute for Therapy through the Arts, and is designed to help dementia patients who are losing their ability to communicate verbally with loved ones.

In the program, a live ensemble plays music from a patient’s youth. The patient and their caregiver are encouraged to interact with the music together by singing, dancing or playing simple instruments like shakers, drums or tambourines.

It’s well-established that even as dementia wreaks havoc on the mind and memories, the degenerative brain disorder doesn’t appear to affect a person’s ability to enjoy music until much later in the disease course, said senior researcher Dr. Borna Bonakdarpour. He is an associate professor of neurology at Northwestern University Feinberg School of Medicine, in Chicago.

Because of this, patients can retain their ability to dance and sing long after their ability to talk has diminished.

“They can process music, they can get it, they receive it, they respond to it, they can dance with it, they can play with it, they can sing along with it,” Bonakdarpour said. “These are components that are pretty much intact, which is amazing.”

The Alzheimer’s Association recognizes music therapy as an important non-drug therapy for dementia, said Sam Fazio, senior director for psychosocial research and quality care.

“You’re accessing different parts of the brain that may not be affected by the disease’s symptoms,” Fazio said. “Sometimes when people can no longer express themselves in words, they can still express themselves with lyrics of a song or feel the melody.”

Helping patients and caregivers

For this study, Bonakdarpour’s team asked 21 patients and their caregivers to take part in the Musical Bridges to Memory program once a week. The study was unusual because earlier music therapy efforts have tended to focus solely on the patient, while this involved both patients and caregivers.

The program included 45 minutes of music, as well as a 15-minute talk beforehand so the music therapist could discuss specific communication skills to be addressed during the time together. Overall, patients took part in 12 sessions over three months.

The patient/caregiver pairs also were videotaped for 10 minutes before and 10 minutes after each session, so research assistants could analyze the effect music therapy had on their interactions, Bonakdarpour said.

While the program is designed to help access the musical part of a patient’s brain, these sessions also counsel caregivers on ways to patiently engage with their loved one, Bonakdarpour said.

“Things can get escalated between the patient and caregiver because the care partner doesn’t know what to do with abnormal behaviors,” he said. “A patient with a memory problem may ask the same question 10 times, and the partner can get exasperated.”

Wes and Susan took part in the program virtually because of the COVID-19 pandemic.

The music included old standards like “You Are My Sunshine,” “Take Me Out to the Ballgame,” and “You’re a Grand Old Flag,” but the musicians took requests, Susan said. She and Wes love Josh Groban, so the ensemble added some of his tunes to their repertoire.

“She would play videos and she’d do an opening and an ending song,” Susan recalled. “She asked what we wanted to hear, and she would play it for us, and then we would sing along. I was right next to him, so I would often look into his face, and we’d connect that way.”

The researchers found that non-verbal social interactions significantly increased between the patients and caregivers who took part in the program, while communication declined among eight patient/caregiver pairs who did not participate and served as a control group.

In group conversations after the music, patients were more socially engaged, the researchers said. They maintained eye contact more often, were less distracted and agitated, and were in an upbeat mood.

Bonakdarpour remembered one particular patient “who was very hyperactive and during the sessions would get up and wanted to dance with everybody. The wife was kind of embarrassed, and she would get mad at him.”

“But then as the sessions moved forward, and by the middle to end, this guy was sitting down during all the sessions with his wife,” Bonakdarpour said. “They’re communicating. They’re using percussion instruments to participate. They dance together. So it really changed their relationship.”

‘It just makes him happy’

Based on these results, Bonakdarpour’s team has received a three-year grant from the National Endowment for the Arts to expand the program and perform another clinical trial involving more patients.

Fazio praised the study because it was done with professional music therapists and with the right protocols so it could have the best possible outcomes.

“Sometimes people think they’re doing music therapy by just playing a record in the background, when that’s not really true,” Fazio said. “To have the outcomes we want, like increased engagement and less anxiety or agitation, the correct protocols need to be in place by trained music therapy professionals who understand how to use music to accomplish non-musical goals.”

Bonakdarpour is convinced that music therapy should be an important part of helping manage the symptoms of dementia patients whose capabilities are declining.

“For some of these psychiatric issues of people with dementia, we don’t have great drugs,” he said. “When we’re really desperate, we have to use some drugs that have side effects. Some of them can really affect the heart. It can even shorten people’s lives. And if you can avoid using these toxic medications, wouldn’t that be great?”

Wes enjoyed the program so much that Susan now incorporates music into their regular visits, she said. She asks an Amazon device to play a list of songs.

“Alexa plays those songs and then we just play along with the instruments. I try to find songs that he’ll remember. It just makes him happy,” Susan said.


Source: HealthDay

How Music Affects Memory in Those with Dementia

Most people aren’t connected to music the way Tony Bennett is, but virtually everyone has songs they love. And music can reengage a person with dementia.

“When my father was in hospice in the last weeks of his life, he had been unable to speak for a while and wasn’t responding to us,” says Daniel Potts, MD, FAAN, a neurologist at VA Tuscaloosa Health Care and author of A Pocket Guide for the Alzheimer’s Caregiver. “We’re a singing family, so we called everybody who used to sing with us. Most of them came, and we just sat around his bedside and sang…and he sang with us. We’ll never forget that.”

Over the past two decades, a substantial body of research has demonstrated that music in all its forms arouses, stimulates, and organizes many areas of the brain. “Songs of personal meaning stimulate memories, even for people who have trouble accessing their memories, because of the various ways networks that form information in the brain get recruited,” says Concetta Tomaino, DA, executive director and co-founder of the Institute for Music and Neurologic Function in New York City. “Imaging studies have shown that there is an area of convergence in the medial prefrontal cortex [a region that holds onto and retrieves memories] that lights up in the brain when we hear music that’s important to us.

“Music that’s personal has many elements that help us recall information. It affects us emotionally, it connects us to people and places, and we tend to relive it and listen to it many times throughout our lives, which strengthens those connections even more,” Dr. Tomaino says.

In a study published in Brain in 2015, European researchers examined a group of people with Alzheimer’s disease by using brain imaging technologies and compared them with young, healthy participants. The scientists found that the areas of the brain that encode musical memory show very little damage in Alzheimer’s.

And researchers at the University of Utah, who published their results in the Journal of Prevention of Alzheimer’s Disease in 2019, found that playing personally meaningful music for people with Alzheimer’s disease stimulated those areas of the brain and improved mood. “We had patients and their families identify music they liked. Then we used an MP3 player to develop a playlist and asked them to listen to it over several weeks,” says Norman L. Foster, MD, FAAN, professor of neurology at the University of Utah and one of the lead authors of the study. They then used functional MRIs to see which regions of the brain were activated when patients listened to their favorite music.

They found that several key regions of the brain—including the visual network, the salience network (regions that decide which stimuli deserve our attention), the executive network (which performs high-level cognitive tasks such as reasoning and problem-solving), and the cerebellar and corticocerebellar network pairs (for visual attention and working memory)—showed significantly higher-level functional connections. “Language and visual memory pathways are damaged early as the disease progresses, but personalized music programs can activate the brain, especially for patients who are losing contact with their environment,” Dr. Foster says.

That kind of reconnection produces tangible results. Music & Memory, a nonprofit organization in Mineola, NY, helps nursing homes and family caregivers create and manage playlists. A study published in the Journal of the American Medical Directors Association in March 2020 found that the Music & Memory program significantly reduced the need for anti-anxiety, antipsychotic, and antidepressant medications in nursing home residents. It also led to significant declines in aggressive behavior, depressive symptoms, pain, and falls.

To make the most of the power of music for someone with dementia, consider these four expert-recommended strategies.

Make it personal. Find out what music is meaningful to the person, says Dr. Potts. Songs from the “reminiscence bump”—between the ages of 10 and 30, when emotion tends to be heightened—have extra staying power. “Those songs really stoke the autobiographical memory,” Dr. Potts says. (This is why general “music therapy” groups in long-term care facilities may not be as helpful; if people listened to different types of music when they were younger, they might not respond to the same music.)

Participate. “In our support groups, we find that it isn’t just putting on music that people like; it’s also engaging with them—singing along, keeping the beat with them,” says Jonathan Graff-Radford, MD, division chair of behavioral neurology at Mayo Clinic in Rochester, MN. “See which songs trigger more engagement—people may clap their hands, sing, or tap their feet—and then play those songs more frequently and eliminate ones that don’t seem to do the trick.”

Add it to the routine. “Don’t just play the music once in a while; make it a regular part of their days,” Dr. Graff-Radford says. “But avoid overdoing it, keep the volume at an appropriate level, and take a break if they seem to be overstimulated.”

Use it strategically. “Music can be very helpful when the person gets difficult or is agitated,” says Dr. Tomaino. “Don’t fight with the person; instead, find a piece of music and see if you can engage the person.” Dr. Tomaino remembers a couple who loved big-band and swing music and used to go out dancing. After the wife was diagnosed with Alzheimer’s disease, she became obstinate when it was time for bathing and personal care. To budge her from the chair, her husband would put on a Duke Ellington album and extend a hand as if asking her to dance. She recognized that and would take his hand, and he’d gently dance her over to the bathroom. “It’s the context, the feelings, the personal connections embodied in music that stay with us forever.”


Source: Brain&Life

Lifetime of Knowledge Can Clutter Memories of Older Adults

When a person tries to access a memory, their brain quickly sifts through everything stored in it to find the relevant information. But as we age, many of us have difficulty retrieving memories. In a review publishing in the journal Trends in Cognitive Sciences on February 11, researchers propose an explanation for why this might be happening: the brains of older adults allocate more space to accumulated knowledge and have more material to navigate when attempting to access memories. While this wealth of prior knowledge can make memory retrieval challenging, the researchers say it has its upsides — this life experience can aid with creativity and decision-making.

Researchers of Columbia University, Harvard University, and University of Toronto looked at several behavioral and neuroimaging studies, which show that older adults have difficulty suppressing information that is no longer relevant and that when searching for a specific memory, they often retrieve other, irrelevant memories along with it. The studies also showed that when given a cognitive task, older adults rely more heavily on previous knowledge than younger adults do.

While the researchers focus primarily on the difficulties that these cluttered memories may pose, they also highlight a few situations in which these crowded memoryscapes may be useful. “Evidence suggests that older adults show preserved, and at times enhanced, creativity as a function of enriched memories,” the researchers write. They further hypothesize that older adults may be well served by their prior knowledge when it comes to decision-making, where they can pull on their accumulated wisdom.

With continued study and increased understanding of how memory works in older adults, researchers are hopeful that they may be able to find new ways to help them. They write, “It is possible that the increased binding and richer encodings of older adults can even be leveraged to improve older adults’ learning and memory.”


Source: Science Daily

Some Blood Pressure-lowering Meds Linked to Less Memory Decline in Older Adults

Older adults taking blood pressure-lowering medications known to cross the blood-brain barrier had better memory recall over time compared to those taking other types of medicines to treat high blood pressure, according to new research published today in the American Heart Association journal Hypertension.

High blood pressure, or hypertension, is a risk factor for cognitive decline and dementia in older adults. Nearly half of American adults have elevated blood pressure. Treating high blood pressure with blood pressure-lowering medicines reduced the cases of mild cognitive impairment by 19% in one large trial (SPRINT MIND).

ACE inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers and diuretics are different classes of blood pressure-lowering medicines. Each class acts in a different way to reduce blood pressure, and some cross the blood-brain barrier, thereby impacting cognitive function.

“Research has been mixed on which medicines have the most benefit to cognition,” said study author Daniel A. Nation, Ph.D., ​an associate professor of psychological science in the Institute for Memory Impairments and Neurological Disorders at the University of California, Irvine. ”Studies of angiotensin II receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors have suggested these medicines may confer the greatest benefit to long-term cognition, while other studies have shown the benefits of calcium channel blockers and diuretics on reducing dementia risk.”

This is the first meta-analysis to compare the potential impact over time of blood pressure lowering medicines that do vs. those that do not cross the blood-brain barrier. The medicines were evaluated for their effects on several cognitive domains, including attention, language, verbal memory, learning and recall.

“Hypertension occurs decades prior to the onset of dementia symptoms, affecting blood flow not only in the body but also to the brain,” Nation said . “Treating hypertension is likely to have long-term beneficial effects on brain health and cognitive function later.”

Researchers gathered information from 14 studies of nearly 12,900 adults ages 50 years and older. These included studies done in the United States, Australia, Canada, Germany, Ireland and Japan. The meta-analysis found:

  • Older adults taking blood pressure-lowering medicines that cross the blood-brain barrier had better memory recall for up to 3 years of follow-up compared to those taking medicines that do not cross the blood-brain barrier even though they had a higher level of vascular risk.
  • Adults taking hypertension medications that did not cross the blood-brain barrier had better attention for up to 3 years of follow-up.

“These findings represent the most powerful evidence to-date linking brain-penetrant ACE-inhibitors and angiotensin receptor blockers to better memory. It suggests that people who are being treated for hypertension may be protected from cognitive decline if they medications that cross the blood-brain barrier,” said study co-author Jean K. Ho, Ph.D., a postdoctoral fellow at the University of California, Irvine.

Blood pressure is considered elevated at 120/80 mm Hg and higher. The current American Heart Association/American College of Cardiology guidelines for treating high blood pressure suggest changes to diet and activity levels to lower blood pressure and adding blood pressure-lowering medication for people with levels of 130/80 mm Hg or higher depending on their risk status. If blood pressure reaches 140/90 mm Hg, blood pressure-lowering medication is recommended.

Limitations of this analysis are that the authors could not account for differences in racial/ethnic background based on the available studies, and there is a higher proportion of men vs. women in the group who took medications that cross the blood-brain barrier. This is an important area of future research since previous studies have shown that people from various racial/ethnic backgrounds may respond differently to different blood pressure medications.


Source: American Heart Association

A Neuroscientist’s Poignant Study of How We Forget Most Things in Life

David Kortava wrote . . . . . . . . .

Any study of memory is, in the main, a study of its frailty. In “Remember,” an engrossing survey of the latest research, Lisa Genova explains that a healthy brain quickly forgets most of what passes into conscious awareness. The fragments of experience that do get encoded into long-term memory are then subject to “creative editing.” To remember an event is to reimagine it; in the reimagining, we inadvertently introduce new information, often colored by our current emotional state. A dream, a suggestion, and even the mere passage of time can warp a memory. It is sobering to realize that three out of four prisoners who are later exonerated through DNA evidence were initially convicted on the basis of eyewitness testimony. “You can be 100 percent confident in your vivid memory,” Genova writes, “and still be 100 percent wrong.”

Forgetfulness is our “default setting,” and that’s a good thing. The sixty or so members of our species whose brains are not sieves have their own diagnosis: highly superior autobiographical memory, or hyperthymesia. While the average person can list no more than ten events for any given year of life, people living with H.S.A.M. “remember in excruciatingly vivid detail the very worst, most painful days of their lives.” The most studied case concerns Solomon Shereshevsky, an early-twentieth-century Russian journalist who, like Borges’s Funes the Memorious, “felt burdened by excessive and often irrelevant information and had enormous difficulty filtering, prioritizing, and forgetting what he didn’t want or need.” Desperate to empty his mind, Shereshevsky practiced, with some success, various visualization exercises: he’d imagine setting fire to his memories or picture them scrawled on a giant chalkboard and then erased. (He also turned to the comforts of the bottle and died of complications from alcoholism, although Genova doesn’t mention this.)

An efficient memory system, Genova writes, involves “a finely orchestrated balancing act between data storage and data disposal.” To retain an encounter, deliberate attention alone will get you most of the way there. “If you don’t have Alzheimer’s and you pay attention to what your partner is saying, you’re going to remember what they said.” (Distracted spouses, take note.) Also, get enough sleep. (An exhausted Yo-Yo Ma once left his eighteenth-century Venetian cello, worth $2.5 million, in the trunk of a New York City yellow cab.) Other strategies include leaning on external cues, such as checklists—every year, U.S. surgeons collectively leave hundreds of surgical instruments inside their patients’ bodies—chunking information into meaningful units, and the method of loci, or visualizing information in a familiar environment. Joshua Foer employed the latter device, also known as a “memory palace,” to win the 2006 U.S. Memory Championship.

The business of “motivated forgetting” is more complicated. Genova advises aspiring amnesiacs to avoid anything that might trigger an unwanted memory. “The more you’re able to leave it alone, the more it will weaken and be forgotten,” she writes. Easier said than done, especially with respect to the recurring, sticky memories that characterize conditions such as P.T.S.D. Here, Genova points to promising therapies that take advantage of the brain’s natural tendency to edit episodic memories with every retrieval. In the safe keeping of a psychiatrist’s office (and sometimes with the benefit of MDMA), a patient deliberately revisits the painful memory “with the intention of introducing changes,” revising and gradually overwriting the panic-inducing memory with a “gentler, emotionally neutral version of what happened.” Not quite “Eternal Sunshine,” but if it works, it works.

Genova, a neuroscientist by training, has spent most of her working life writing fiction about characters with various neurological maladies. Her novel “Still Alice,” from 2007, centered on a Harvard psychology professor who is diagnosed with early-onset Alzheimer’s. In “Remember,” her first nonfiction work, Genova assures her readers that only two per cent of Alzheimer’s cases are of the strictly inherited, early-onset kind. For most of us, our chances of developing the disease are highly amenable to interventions, as it takes fifteen to twenty years for the amyloid plaque that is mounting in our brains to reach a tipping point, “triggering a molecular cascade that causes tangles, neuroinflammation, cell death, and pathological forgetting.” What do those interventions look like? Genova’s guidance is backed by current science, but is mostly just parental: exercise, avoid chronic stress, adopt a Mediterranean diet, and enjoy your morning coffee—but not so much as to compromise deep sleep, which is when “your glial cells flush away any metabolic debris that has accumulated in your synapses.”

One of the more interesting studies that Genova cites followed six hundred and seventy-eight elderly nuns over two decades, subjecting them to all manner of physical and cognitive tests. When a nun died, her brain was collected for autopsy. Curiously, a number of the nuns whose brains showed plaques, tangles, and shrinkage exhibited “no behavioral signs” of Alzheimer’s disease. The researchers theorized that these nuns had a high degree of “cognitive reserve”; they tended to have more years of formal education, active social lives, and mentally stimulating hobbies. Even as many old neural pathways collapsed, they were paving “new neural roads” and taking detours along as-yet undamaged connections, thereby masking, if not postponing, the onset of the disease. All pretty straightforward. Now all we have to do is build a society in which everyone has the time and resources for adequate sleep, exercise, nutrition, self-care, and a few good hobbies.


Source : The New Yorker