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Brain Secrets of the Super-Sharp ‘Super-Agers’

Amy Norton wrote . . . . . . . . .

Researchers have discovered another clue as to how some older people stay sharp as a tack into their 80s and beyond: Their brain cells are really big.

The study focused on what scientists have dubbed “super-agers” — a select group of elderly adults who have the memory skills of people decades younger.

The researchers found that in a memory-related area of the brain, super-agers had larger neurons than elderly adults with average brain power — and even in comparison to people 30 years their junior.

What’s more, those big brain cells were relatively free of “tau tangles,” one of the key markers of Alzheimer’s disease.

Tau is a protein that, in healthy brain cells, helps stabilize the internal scaffolding. But abnormal versions of tau — ones that cling to other tau proteins — can develop as well.

In people with Alzheimer’s, the brain is marked by a large accumulation of those tau tangles, as well as “plaques” — clumps of another protein called amyloid.

Researchers at Northwestern University, in Chicago, have been studying super-agers for years. In previous work the investigators found that those unusually sharp seniors are similar to their cognitively average peers when it comes to amyloid plaques: Both groups have comparable amounts in their brains.

Where they differ is in tau buildup. Super-agers have far fewer tau tangles in a memory-related area of the brain called the entorhinal cortex.

The new study, published in the Journal of Neuroscience, adds to that picture. Super-agers also have larger neurons (nerve cells) in the entorhinal cortex.

“The study of super-aging establishes the principle that dementia is not inevitable — that withstanding ‘abnormal aging’ is possible,” said lead researcher Tamar Gefen. She is an assistant professor of psychiatry and behavioral sciences at Northwestern’s Feinberg School of Medicine.

It also highlights the link between tau accumulation and the dementia process, Gefen said. Historically, amyloid plaques have gotten most of the attention, she noted — with drug development mainly aimed at reducing amyloid plaques in the brain.

Now, Gefen said, “it’s generally accepted among the scientific community that amyloid is not the only culprit. There are several targets, amyloid and tau included, that need to be considered in the fight against Alzheimer’s pathology.”

Based on the new findings, she said, her team suspects that tau tangles may cause neurons to shrink.

There are many unknowns about super-agers — including how many are out there, and why their brains resist age-related decline. It’s likely a mix of good genes and lifestyle factors, and Gefen said the super-ager study is trying to figure what, exactly, those factors might be.

Understanding why some seniors cognitively thrive into their 80s, 90s and beyond will also help researchers understand why so many others develop dementia.

“In order to more fully understand dementia risk, it is important for researchers to examine both sides of the coin,” said Claire Sexton, senior director of scientific programs and initiatives at the Alzheimer’s Association.

“In those people found to be consistently more resistant, what can we learn from them to help others reduce their risk of Alzheimer’s or other dementia?” said Sexton, who was not involved in the study.

She agreed that the new findings highlight tau as a key player.

“While much of the limelight is currently on anti-amyloid therapies for Alzheimer’s,” Sexton said, “these new findings align with a growing focus on the role of tau in neurodegenerative disease.”

Sexton noted that the Alzheimer’s Association is funding a number of studies developing experimental anti-tau therapies. And earlier this year, researchers launched the first trial to test a combination of drugs targeting both amyloid and tau.

The current findings are based on autopsied brain tissue from six elderly adults who’d participated in the super-ager study before their deaths and agreed to donate their brains for research. Their tissue samples were compared against donated brain tissue from seven “cognitively average” seniors, five elderly adults with early-stage dementia, and six healthy adults 20 to 30 years younger.

Overall, Gefen’s team found, super-agers had larger neurons, with far less tau, in the entorhinal cortex, versus both groups of older adults.

Surprisingly, their neurons were even larger than the younger group’s — some of whom were only in their 40s, Gefen noted.

It’s not clear why. But, Gefen said, it’s possible that super-agers are equipped with those larger neurons at birth.

She speculated that the super-size neurons may “harbor features,” as yet unknown, that help them resist tau-tangle formation. Resistance to tau, in turn, might protect the neurons from shrinking.

Source: HealthDay

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

Moderate Drinking Linked to Brain Changes and Cognitive Decline

Consumption of seven or more units of alcohol per week is associated with higher iron levels in the brain, according to a study of almost 21,000 people publishing in the open access journal PLOS Medicine. Iron accumulation in the brain has been linked with Alzheimer’s and Parkinson’s diseases and is a potential mechanism for alcohol-related cognitive decline.

There is growing evidence that even moderate alcohol consumption can adversely impact brain health. Anya Topiwala of the University of Oxford, United Kingdom, and colleagues explored relationships between alcohol consumption and brain iron levels. Their 20,965 participants from the UK Biobank reported their own alcohol consumption, and their brains were scanned using magnetic resonance imaging (MRI). Almost 7,000 also had their livers imaged using MRI to assess levels of systemic iron. All individuals completed a series of simple tests to assess cognitive and motor function.

Participants’ mean age was 55 years old and 48.6% were female. Although 2.7% classed themselves as non-drinkers, average intake was around 18 units per week, which translates to about 7½ cans of beer or 6 large glasses of wine. The team found that alcohol consumption above seven units per week was associated with markers of higher iron in the basal ganglia, a group of brain regions associated with control of motor movements, procedural learning, eye movement, cognition, emotion and more. Iron accumulation in some brain regions was associated with worse cognitive function.

This is the largest study to date of moderate alcohol consumption and iron accumulation. Although drinking was self-reported and could be underestimated, this was considered the only feasible method to establish such a large cohort’s intake. A limitation of the work is that MRI-derived measures are indirect representations of brain iron, and could conflate other brain changes observed with alcohol consumption with changes in iron levels.

Given the prevalence of moderate drinking, even small associations can have substantial impact across whole populations, and there could be benefits in interventions to reduce consumption in the general population.

Topiwala adds, “In the largest study to date, we found drinking greater than 7 units of alcohol weekly associated with iron accumulation in the brain. Higher brain iron in turn linked to poorer cognitive performance. Iron accumulation could underlie alcohol-related cognitive decline.”

Source: Science Daily

Study: Latin Dance May Boost Your Aging Brain

Cara Murez wrote . . . . . . . . .

Latin dance classes may be a great workout and social outlet, but new research suggests that learning the intricate steps of the salsa, samba and merengue may also improve your memory.

In the study, a Latin dance program was offered to more than 300 Spanish speakers over four years at 12 different sites in Chicago.

After eight months of classes, assessments found significant improvement in participants’ working memory scores. Working memory is a type of short-term memory used to keep small amounts of information in mind while partaking in other cognitive tasks.

“We think it worked for several reasons. More time being spent active, that could be a reason. It could be the different components of the dance program itself,” said study author Susan Aguinaga, who worked on the program from its inception while a graduate student at the University of Illinois in Chicago. She is now a professor of kinesiology and community health at the University of Illinois at Urbana-Champaign.

“It’s an appealing type of physical activity that they want to continue engaging with,” Aguinaga explained. “In general, populations have a hard time maintaining their physical activity levels, but when it’s an activity that they actually enjoy, then they will be more likely to maintain that activity for longer periods of time.”

It could also simply be the music that’s playing, intriguing dance styles or an activity that’s aerobic, which has previously been shown to improve cognitive performance, Aguinaga said.

“The takeaway is definitely finding an activity that is enjoyable, that is appealing. And if dancing is that activity that provides enjoyment and physical activity and social support, then I think this is an activity that should be promoted more,” Aguinaga said.

The study was a randomized, controlled trial that tested BAILAMOS (Balance and Activity in Latinos, Addressing Mobility in Older Adults), which was co-created by study co-author David Marquez, director of the Exercise and Psychology Lab at the University of Illinois, Chicago, and Miguel Mendez, creator and owner of the Dance Academy of Salsa in Illinois. The program includes merengue, salsa, bachata and cha-cha-cha dancing.

In the study, just over 330 Spanish-speaking Hispanic adults were assigned either to twice weekly dance sessions for eight months or to the control group, which had once-weekly health education classes for four months.

The dancers were led by a professional instructor for the first four months, then during the “maintenance phase” were led by participants assigned as “program champions” for their leadership skills and enthusiasm.

While the study found no difference between the groups in cognitive tests at four months, after eight months people in the dance group had better scores.

In dance classes, a person learns several steps and then need to recall those steps the following week and turn them into sequences, Aguinaga explained. Researchers thought the process of recalling steps could target different aspects of memory, but in a fun way.

About 12% of older Hispanics in the United States currently are living with an Alzheimer’s disease diagnoses, the study noted. That number is estimated to increase by 832% by 2060.

“For older Latinos, the thought of promoting dance as exercise is very appealing, given that older Latinos are familiar with dance in some way. They’ve grown up with it, maybe they’ve danced in the past and it’s something that they enjoy,” Aguinaga said. “It might not even be perceived as exercise because it’s a fun activity.”

About 85% of the study participants were women. They had an average age of 65 and their BMI (body mass index) would categorize them as obese.

Program participants reported feeling better overall, making friends and being better able to manage chronic diseases such as high blood pressure and diabetes, Aguinaga said.

A similar program could potentially benefit people of other races and ethnicities if organizers promoted dances and music that was appealing to whatever population they were targeting, she added.

The findings were published recently in Frontiers in Aging Neuroscience.

Dr. Zaldy Tan is medical director of the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai Medical Center, in Los Angeles. He said, “I think that’s one of the strengths of the study is that the population studied and intervention were appropriate and consistent,” noting that the program was specific and culturally sensitive.

“That’s one thing that I always tell my patients is that physical activity is good for them. Good for their heart, good for their brain, but they must pick a physical activity that’s sustainable, that is consistent to their lifestyle,” said Tan, who was not involved with the new study.

Tan said past research on physical activity has been consistent in that it seems to help people maintain their memory and their thinking skills. One of his own studies found that people who had higher rates of physical activity had more robust brains and a lower risk of dementia.

“The exact mechanism is unclear. Certain theories include the fact that exercise produces better blood flow and improves circulation, and improves vascular health. Of course, the brain is a very vascular organ. It requires a lot of blood flow, a lot of oxygen. So, that’s one way that it could benefit it,” Tan said.

Another theory is that exercise induces specific factors that stimulate brain cell growth and health, Tan added.

Senior and community centers are in a great position to create programs like this, though the pandemic has hampered in-person classes for seniors, he noted.

Tan said that while healthy diet, sleep and socialization are all important, exercise is the number one intervention he recommends to patients who have memory issues, or those who may not yet have memory problems but are interested in preserving their health.

“There are really multiple benefits associated with that. Increased strength, better balance, improved memory and, overall, increased cardiovascular health,” Tan said. “It’s something that definitely we should be encouraging.”

Source: HealthDay

Learn About Confabulation, Also Known as “Honest Lying”

Susan Fitzgerald wrote . . . . . . . . .

In detailed and vivid language, a middle-aged woman talked about her plans for the day and how she had arranged the rooms in the house where she was staying. She explained that in the morning she had awakened, packed her suitcase, and said goodbye. She was off to look after her little boy, who needed to be fed.

The woman’s account, while seemingly ordinary, was extraordinary to the researchers who wrote about it in the journal Brain in 1996. Nothing the 58-year-old woman said was true. The house was a hospital, and her hungry little boy was a grown man. As the scientists noted, this story was a case of confabulation, an unusual neurologic phenomenon in which people talk, often with great flourishes, about events or experiences in their lives—unaware that their stories are false.

“Confabulation is an intriguing disorder of memory and thought. Patients tell stories about their recent doings and plans for the future that are blatantly incompatible with reality,” says Armin Schnider, MD, professor of neurorehabilitation at the University of Geneva in Switzerland, who wrote about the woman in various medical journals and is considered a leading authority on the disorder.

“In contrast to lying, confabulation is not intentional and, in many cases, not even consciously perceived by the confabulator,” says Dr. Schnider. Because there is no intent to deceive and nothing to be gained, confabulation is sometimes referred to as “honest lying” by researchers.

Confabulation usually happens after a brain injury, whether from trauma, a stroke, or a tumor. The woman described by Dr. Schnider had bleeding in her brain from a ruptured aneurysm. In another case referenced in the same article, a 45-year-old man sustained a head injury in a motorcycle accident. After regaining consciousness and being transferred to a rehabilitation ward, the charming and chatty man told stories, some true, others imaginary, according to his relatives.

The man occasionally acted on his confabulations. One time he went to a physician’s office in the ward and asked if he could use the telephone to arrange a deer hunt for that afternoon with his friends. Another time he told a physician he was worried that he might not get leave from his military duties the next day.

Scrambling Reality

Frequently confabulations contain shreds of truth, with some details perhaps drawn from a snippet of conversation, a photograph, or a television show. The woman wanting to feed her little boy, for instance, did have children, but they were all adults. In other cases, a confabulation may touch on a pastime or habit from a person’s life preceding the brain injury or relate in some way to a sad or even happy event from the past.

“Most confabulations become obvious in a discussion about recent doings or plans for the day,” says Dr. Schnider, author of The Confabulating Mind: How the Brain Creates Reality (Oxford University Press, 2018). “They reflect a confusion of current reality,” he says. “Subjects perceive themselves in another time, place, and situation—often related to their near or distant past—and act according to this feeling.”

The term was likely introduced into medical literature in the early 1900s by Carl Wernicke, a German physician who characterized it as “the emergence of memories of events and experiences that never happened.” The exact mechanisms of confabulation may vary from one case to another, but usually it’s due to damage or dysfunction of the front part of the brain, says Dr. Schnider. There’s a preconscious mechanism in this part of the brain that Dr. Schnider calls the orbitofrontal reality filter, which flags thoughts and memories that don’t correlate with reality. “Severe confabulations also may occur in conjunction with delirium, advanced dementia, or uncontrolled psychosis where brain damage is less local.”

Even healthy people experience some degree of faulty memory at one time or another. It may involve a favorite story from childhood or college days that as it is told and retold over time has some details mixed up. Such instances “reflect normal alterations of memory traces over time, which are particularly likely to occur when the memory of an event is weak and the false information is plausible,” says Dr. Schnider.

Some people also embellish. They recount a real event or experience but exaggerate a bit, adding details that didn’t quite happen as told.

Confabulation differs from delusional thinking, which typically is part of a psychiatric disorder, such as schizophrenia, and involves an unshakable belief in something that has no basis in reality.

“Normally we think of our memory as a repository of things that have happened,” says Sara Manning Peskin, MD, assistant professor of clinical neurology at the University of Pennsylvania in Philadelphia. When memory loss stems from a brain injury or disease, she says, a person may unknowingly “fill in gaps in their memory with new memories that never really happened.

“You create a prior reality,” says Dr. Manning Peskin, who writes about confabulation in her new book, A Molecule Away from Madness: Tales of the Hijacked Brain (W.W. Norton & Company, 2022).

Though confabulation is not intentional, it may have the effect of boosting a person’s sense of worth or helping a person make sense of a confusing situation.

Vitamin Deficiency

In her book, Dr. Manning Peskin chronicles a case of confabulation brought on by severe alcoholism, a condition known as Korsakoff’s syndrome. Excessive drinking and poor nutrition can cause a deficiency in thiamine, a B vitamin, which can lead to brain damage. Dr. Manning Peskin describes Lisa Park, a woman with alcohol use disorder who spun fantastical stories. A picture of a celebrity, for instance, triggered a detailed but untrue tale of Park’s brush with fame. Her confabulation eased after she received high doses of thiamine intravenously.

Confabulation is not easy to spot. The tales are often told with such sincerity that “you might assume the person’s word was fact,” Dr. Manning Peskin says.

Another group prone to confabulation is children with fetal alcohol syndrome disorder, says Jerrod Brown, PhD, assistant professor at Concordia University in St Paul, MN. A variety of factors, including social, emotional, and intellectual immaturity and poor impulse control, contributes to the problem, he says. It may be difficult for parents to sort out truth from falsehood, leading to arguments and mistrust of their children. “It can get in the way of family relationships,” says Dr. Brown, who has done podcasts on the subject. He says superficial chattiness or excessive storytelling may be signs of a problem.

Possible Treatments

Confabulation generally falls into two subtypes, provoked and spontaneous, says Dr. Brown, who co-authored a review article on the condition in 2017 in the International Journal of Neurology and Neurotherapy. Provoked instances are usually in response to a question the person feels compelled to answer (“What did you do last night?”). Spontaneous ones are when the person volunteers false information unprompted (“Last night I went to…”).

Confabulation may seem relatively harmless, but it can be stressful and hurtful for family members and caregivers, who may equate it with lying or find it tedious and embarrassing. People who engage in confabulation also may be vulnerable to manipulation, Dr. Brown says, which could have legal repercussions if they make false statements or confessions to police or in court.

Because there are many causes of confabulation, there is no one general treatment. The phenomenon may fade as the underlying condition is resolved, Dr. Schnider says. Keeping “memory” diaries to record real events may be useful for recalling what actually happened yesterday or a while ago. Occasionally medications such as antipsychotics may be helpful, he says.

Questionnaires can be used to evaluate patients with memory problems, says Dr. Schnider. “They do not, however, replace observing the behavior of patients to see if how they behave agrees with what they are saying,” he adds. Because doctors may not always be able to sort out what’s true from what isn’t when evaluating a new patient, family members can play an important role in helping verify information.

Otherwise, it isn’t necessary to correct a confabulation as long as the person is in a safe environment and the false memories can’t lead to dangerous behavior, Dr. Schnider says.

“The study of confabulation has led to ways to explore how the brain distinguishes between thoughts that refer to current reality and thoughts that do not, such as fantasies and daydreams,” says Dr. Schnider. Understanding more about the disorder, he says, will help reveal “how we sense reality.”

Source: Brain&Life


Type 2 Diabetes Accelerates Brain Aging and Cognitive Decline

Scientists have demonstrated that normal brain aging is accelerated by approximately 26% in people with progressive type 2 diabetes compared with individuals without the disease, reports a study published today in eLife.

The authors evaluated the relationship between typical brain aging and that seen in type 2 diabetes, and observed that type 2 diabetes follows a similar pattern of neurodegeneration as aging, but which progresses faster. One important implication of this finding is that even typical brain aging may reflect changes in the brain’s regulation of glucose by insulin.

The results further suggest that by the time type 2 diabetes is formally diagnosed, there may already be significant structural damage to the brain. Sensitive ways to detect diabetes-associated changes to the brain are therefore urgently needed.

There is already strong evidence linking type 2 diabetes with cognitive decline, yet few patients currently undergo a comprehensive cognitive assessment as part of their clinical care. It can be difficult to distinguish between normal brain aging that begins in middle age, and brain aging caused or accelerated by diabetes. To date, no studies have directly compared neurological changes in healthy people over the course of their lifespan with changes to those experienced by people of the same age with diabetes.

“Routine clinical assessments for diagnosing diabetes typically focus on blood glucose, insulin levels and body mass percentage,” says first author Botond Antal, a PhD student at the Department of Biomedical Engineering, Stony Brook University, New York, US. “However, the neurological effects of type 2 diabetes may reveal themselves many years before they can be detected by standard measures, so by the time type 2 diabetes is diagnosed by conventional tests, patients may have already sustained irreversible brain damage.”

To define the impact of diabetes on the brain over and above normal aging, the team made use of the largest available brain structure and function dataset across human lifespan: UK Biobank data from 20,000 people aged 50 to 80 years old. This dataset includes brain scans and brain function measurements and holds data for both healthy individuals and those with a type 2 diabetes diagnosis. They used this to determine which brain and cognitive changes are specific to diabetes, rather than just aging, and then confirmed these results by comparing them with a meta-analysis of nearly 100 other studies.

Their analysis showed that both aging and type 2 diabetes cause changes in executive functions such as working memory, learning and flexible thinking, and changes in brain processing speed. However, people with diabetes had a further 13.1% decrease in executive function beyond age-related effects, and their processing speed decreased by a further 6.7% compared to people of the same age without diabetes. Their meta-analysis of other studies also confirmed this finding: people with type 2 diabetes had consistently and markedly lower cognitive performance compared to healthy individuals who were the same age and similarly educated.

The team also compared brain structure and activity between people with and without diabetes using MRI scans. Here, they found a decrease in grey brain matter with age, mostly in a region called the ventral striatum – which is critical to the brain’s executive functions. Yet people with diabetes had even more pronounced decreases in grey matter beyond the typical age-related effects – a further 6.2% decrease in grey matter in the ventral striatum, but also loss of grey matter in other regions, compared with normal aging.

Together, the results suggest that the patterns of type 2 diabetes-related neurodegeneration strongly overlap with those of normal aging, but that neurodegeneration is accelerated. Moreover, these effects on brain function were more severe with increased duration of diabetes. In fact, progression of diabetes was linked with a 26% acceleration of brain aging.

“Our findings suggest that type 2 diabetes and its progression may be associated with accelerated brain aging, potentially due to compromised energy availability causing significant changes to brain structure and function,” concludes senior author Lilianne Mujica-Parodi, Director of the Laboratory for Computational Neurodiagnostics, Stony Brook University. “By the time diabetes is formally diagnosed, this damage may already have occurred. But brain imaging could provide a clinically valuable metric for identifying and monitoring these neurocognitive effects associated with diabetes. Our results underscore the need for research into brain-based biomarkers for type 2 diabetes and treatment strategies that specifically target its neurocognitive effects.”

Source: elife

You’ve Likely Heard of the Brain’s Gray Matter – Here’s Why the White Matter Is Important Too

Christopher Filley wrote . . . . . . . . .

Who has not contemplated how a memory is formed, a sentence generated, a sunset appreciated, a creative act performed or a heinous crime committed?

The human brain is a three-pound organ that remains largely an enigma. But most people have heard of the brain’s gray matter, which is needed for cognitive functions such as learning, remembering and reasoning.

More specifically, gray matter refers to regions throughout the brain where nerve cells – known as neurons – are concentrated. The region considered most important for cognition is the cerebral cortex, a thin layer of gray matter on the brain’s surface.

But the other half of the brain – the white matter – is often overlooked. White matter lies below the cortex and also deeper in the brain. Wherever it is found, white matter connects neurons within the gray matter to each other.

I am a professor of neurology and psychiatry and the director of the behavioral neurology section at the University of Colorado Medical School. My work involves the evaluation, treatment and investigation of older adults with dementia and younger people with traumatic brain injury.

Finding out how these disorders affect the brain has motivated many years of my study. I believe that understanding white matter is perhaps a key to understanding these disorders. But so far, researchers have generally not given white matter the attention it deserves.

Figuring out the white matter

This lack of recognition largely stems from the difficulty in studying white matter. Because it’s located below the surface of the brain, even the most high-tech imaging can’t easily resolve its details. But recent findings, made possible by advancements in brain imaging and autopsy examinations, are beginning to show researchers how critical white matter is.

White matter is comprised of many billions of axons, which are like long cables that carry electrical signals. Think of them as elongated tails that act as extensions of the neurons. The axons connect neurons to each other at junctions called synapses. That is where communication between neurons takes place.

Axons come together in bundles, or tracts, that course throughout the brain. Placed end to end, their combined length in a single human brain is approximately 85,000 miles. Many axons are insulated with myelin, a layer of mostly fat that speeds up electrical signaling, or communication, between neurons by up to 100 times.

This increased speed is crucial for all brain functions and is partly why Homo sapiens have unique mental capacities. While there’s no doubt our large brains are due to evolution’s addition of neurons over eons, there has been an even greater increase in white matter over evolutionary time.

This little-known fact has profound implications. The increased volume of white matter – mainly from the myelin sheaths that surround axons – enhances the efficiency of neurons in the gray matter to optimize brain function.

Imagine a nation of cities that are all functioning independently, but not linked to other cities by roads, wires, the internet or any other connections. This scenario would be analogous to the brain without white matter. Higher functions like language and memory are organized into networks in which gray matter regions are connected by white matter tracts. The more extensive and efficient those connections, the better the brain works.

White matter and Alzheimer’s

Given its essential role in the connections between brain cells, damaged white matter can disturb any aspect of cognitive or emotional function. White matter pathology is present in many brain disorders and can be severe enough to cause dementia. Damage to myelin is common in these disorders, and when the disease or injury is more severe, axons can also be damaged.

More than 30 years ago, my colleagues and I described this syndrome as white matter dementia. In this condition, the dysfunctional white matter is no longer adequately performing as a connector, meaning that the gray matter cannot act together in a seamless and synchronous manner. The brain, in essence, has been disconnected from itself.

Equally important is the possibility that white matter dysfunction plays a role in many diseases currently thought to originate in gray matter. Some of these diseases stubbornly defy understanding. For example, I suspect white matter damage may be critical in the early phases of Alzheimer’s disease and traumatic brain injury.

Alzheimer’s is the most common type of dementia in older individuals. It can impair cognitive function and rob people of their very identity. No cure or effective treatment exists. Ever since Alois Alzheimer’s 1907 observations of gray matter proteins – called amyloid and tau – neuroscientists have believed the buildup of these proteins is the central problem behind Alzheimer’s. Yet many drugs that remove these proteins do not stop the patients’ cognitive decline.

Recent findings increasingly suggest that white matter damage – preceding the accumulation of those proteins – may be the true culprit. As brains age, they often experience gradual loss of blood flow from the narrowing of vessels that convey blood from the heart. Lower blood flow heavily impacts white matter.

Remarkably, there is even evidence that inherited forms of Alzheimer’s also feature early white matter abnormalities. That means therapies aimed at maintaining blood flow to white matter may prove more effective than attempting to dislodge proteins. One simple treatment likely to help is controlling high blood pressure, as this can reduce the severity of white matter abnormalities.

White matter and traumatic brain injury

Patients with traumatic brain injury, particularly those with moderate or severe injuries, can have lifelong disability. One of the most ominous outcomes of TBI is chronic traumatic encephalopathy, a brain disease believed to cause progressive and irreversible dementia. In TBI patients, the accumulation of tau protein in gray matter is evident.

Researchers have long recognized that white matter damage is common in people who have sustained a TBI. Observations from the brains of those with repetitive traumatic brain injuries – football players and military veterans have been frequently studied – have shown that white matter damage is prominent, and may precede the appearance of tangled proteins in the gray matter.

Among scientists, there is a burgeoning excitement over the new interest in white matter. Researchers are now beginning to acknowledge that the traditional focus on the study of gray matter has not produced the results they hoped. Learning more about the half of the brain known as white matter may help us in the years ahead to find the answers needed to alleviate the suffering of millions.

Source: The Conversation

Your Personality May Safeguard Your Aging Brain

Amy Norton wrote . . . . . . . . .

Certain personality traits may make older adults more or less vulnerable to waning memory and thinking skills, a new study suggests.

The study, of nearly 2,000 older adults, found that those high on the “conscientious” scale — organized, self-disciplined and productive — were less likely to develop mild cognitive impairment. That refers to subtler problems with memory and other mental skills that sometimes precede dementia.

On the other end of the spectrum were older folks high in neuroticism — a tendency to be anxious, moody and vulnerable to stress. They had an increased risk of developing mild cognitive impairment, versus people low on the neuroticism scale.

The findings, published April 11 in the Journal of Personality and Social Psychology, add to evidence linking personality to cognitive health as we age.

Personality matters, experts said, because it influences health-related choices ranging from exercise to smoking, as well as broader attitudes — including whether you believe you can make positive changes.

“Personality traits reflect an individual’s persistent patterns of thinking, feeling and behaving,” said Tomiko Yoneda, a postdoctoral researcher at Northwestern University in Chicago, who led the study.

People who are high in conscientiousness, for example, are inclined to eat well, exercise and engage in other healthy behaviors, while avoiding risks like smoking.

Those tendencies may explain their lower risk of developing mild cognitive impairment, according to Yoneda, who was based at the University of Victoria, in Canada, at the time of the study.

In contrast, she said, people high on the neuroticism scale often have “unhealthy coping styles” to deal with anxiety, depression and emotional instability.

Angelina Sutin is a professor at Florida State University College of Medicine who studies personality traits and health.

Sutin agreed that lifestyle behaviors, over the course of a lifetime, are likely a major reason that personality traits are associated with older adults’ memory and thinking skills.

But it goes beyond things like diet, exercise and smoking, too, Sutin said. Personality influences a person’s likelihood of exploring new experiences, for example, or being socially active. Both mental and social stimulation are thought to support healthy brain aging.

There is also evidence linking personality traits to the likelihood of having chronic low-level inflammation in the body — a state that can contribute to a range of diseases.

But lest anxious people get anxious about developing cognitive impairment, Sutin stressed that personality is not “destiny.”

Cognitive decline and dementia are complex, with many factors coming into play. And while personality tends to be relatively stable throughout life, it is not set in stone, either.

Both Sutin and Yoneda pointed to research showing that personality can be nudged in a positive direction when people make concerted efforts to notice and alter certain habitual thoughts and behaviors.

People high in neuroticism, for example, can improve their emotional stability, while dedicated introverts can come out of their shells a bit to be more socially engaged.

“You won’t radically change who you are,” Sutin said. Instead, she added, it’s about making achievable shifts: People high on the neuroticism scale, for instance, could decide to be a little more organized in their daily routines.

The current findings are based on 1,954 older adults who were part of a long-term study of memory and aging that began in the 1990s. Participants answered standard questions gauging personality traits, and then had annual assessments of their cognitive skills, for up to 23 years.

Overall, Yoneda’s team found, the odds of developing mild impairment declined 22% for each 6-point increase on the conscientiousness scale (which ranges from 0 to 48). In contrast, that risk rose by 12% with every 7-point jump on the neuroticism scale (also 0 to 48).

In a related finding, highly conscientious seniors also lived longer in good cognitive health: An 80-year-old, for example, could expect to live an extra two years without impairment, versus a peer who was low on the conscientiousness scale.

Again, though, Sutin stressed that people do not have to be ruled by their personalities.

Instead, she said, understanding your own personality, and how it motivates your thinking and behavior, is helpful: You may be able to “take a step back” when a stressful situation arises, and choose a better coping strategy.

Source: HealthDay

Scientists Discover Genetic Variants that Speed Up and Slow Down Brain Aging

Leigh Hopper wrote . . . . . . . . .

Researchers from a USC-led consortium have discovered 15 “hot spots” in the genome that either speed up brain aging or slow it down — a finding that could provide new drug targets to resist developmental delays, Alzheimer’s disease and other degenerative brain disorders.

The research appeared online in Nature Neuroscience.

“The big game-changer here is discovering locations on the chromosome that speed up or slow down brain aging in worldwide populations. These can quickly become new drug targets,” said Paul Thompson of USC, a lead author on the study and the co-founder and director of the ENIGMA Consortium. “Through our AI4AD [Artificial Intelligence for Alzheimer’s Disease] initiative we even have a genome-guided drug repurposing program to target these and find new and existing drugs that help us age better.”

ENIGMA is working group based at USC that is exploring a vast trove of brain data and has published some of the largest-ever neuroimaging studies of schizophrenia, major depression, bipolar disorder, epilepsy, Parkinson’s disease, and even HIV infection.

To discover the hot spots, or genomic loci, more than 200 ENIGMA-member scientists from all over the world looked for people whose brains were scanned twice with MRI. The scans provided a measure of how fast their brains were gaining or losing tissue in regions that control memory, emotion and analytical thinking.

After computing brain tissue change rates in 15,000 people of all ages, researchers screened a million markers in their genomes to detect 15 genomic loci — specific, physical locations of genes or other DNA sequences on a chromosome — that were speeding up brain tissue changes.

Dementia and Alzheimer’s research implications

These loci included some well-known Alzheimer’s risk genes, such as APOE, and some novel ones, Thompson said. The researchers also found overlap with genes involved with depression, schizophrenia and cognitive functioning.

“Some of these genetic variants affect the growth rates of brain substructures in childhood, while others affect the speed of brain tissue loss in older adulthood,” said co-author Neda Jahanshad, an associate professor of neurology at the Keck School of Medicine of USC. “The different parts of the brain have specific genes associated with their rates of change.”

Thompson added, “You can see that APOE — the famous Alzheimer’s gene — hits a couple of brain structures adversely — the hippocampus and amygdala — which also makes sense as they are the brain regions most vulnerable to Alzheimer’s and it seems to speed tissue loss there specifically.”

ENIGMA also has international projects studying childhood brain disorders — from Tourette syndrome and autism to epilepsy. The new list of genes that slow down or speed up brain growth in children provides new leads to pursue in these disorders as well, the researchers said.

Source: University of Southern California

After COVID-19, Experts Say Watch for These Potential Heart and Brain Problems

Michael Merschel wrote . . . . . . . . .

COVID-19 was full of surprises early on, causing mild problems in the short term for some people and serious complications for others.

Long term, it may be just as capricious.

Studies are spotting potential heart and brain problems up to a year after infection with SARS-CoV-2, even in people who had mild COVID-19.

The possible long-term effects include “a myriad of symptoms affecting different organs,” said Dr. José Biller, director of the COVID-19 neurology clinic at Loyola Medicine in Maywood, Illinois. “So, it could be the lungs, it could be cardiovascular, it could be the nervous system, it could be mental health or behavioral problems.”

Estimates vary widely on how many people may be affected. Research suggests about 10% to 20% of people experience mid- or long-term issues from COVID-19, according to the World Health Organization.

That may sound small, but COVID has affected hundreds of millions of people, said Dr. Siddharth Singh, director of the post-COVID-19 cardiology clinic at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles. In the U.S. alone, about 80 million people have been infected with the coronavirus since the pandemic started in early 2020.

There are many more questions than answers, including about who is most at risk for post-COVID problems and how long the effects might last. But experts say people who have had COVID-19 should be aware of these potential risks:

Heart disease and stroke

A study published in Nature Medicine in February concluded the risk of heart problems one year after COVID-19 infection is “substantial.”

Those heart problems include irregular heartbeats, heart failure (the inability of the heart to pump properly), coronary disease (buildup in arteries that limits blood flow), heart attacks and more.

The study included 153,760 U.S. veterans, most of them white and male, who tested positive for COVID-19 between March 1, 2020, and Jan. 15, 2021, and survived at least 30 days. They were compared to a control group of more than 5.6 million veterans without COVID-19.

Researchers adjusted for pre-existing conditions and found that after one year, those who had COVID-19 were 63% more likely to have some kind of cardiovascular issue, resulting in about 45 additional cases per 1,000 people.

Risks were elevated even among people who did not have severe COVID-19. That matches what Singh has seen in his post-COVID clinic, which began treating patients in December 2020. “A lot of patients that we have seen with long-haul symptoms had minor illness and had been treated at home.”

Singh also treats many people with postural orthostatic tachycardia syndrome, or POTS, which can cause dizziness, fainting and heart palpitations. “These palpitations mostly tend to happen when people are standing or sitting upright,” he said.

In rare cases, “smoldering inflammation around the heart or in the heart” can occur, Singh said.

The Nature Medicine study also found a 52% increased risk of stroke at one year among COVID-19 survivors, or about four extra strokes per 1,000 people.

Brain problems

Among the 113 patients in Biller’s long COVID clinic, almost 3 in 4 reported so-called brain fog. “They are unable to multitask, and have difficulties in learning new skills,” said Biller, who also leads the department of neurology at the Loyola University Chicago Stritch School of Medicine.

A recent Nature study of 785 people ages 51 to 81 found those who had COVID-19 lost more grey matter and had more brain shrinkage than those who had not.

Mental health

A study published in February in BMJ used the same pool of U.S. veterans as the Nature Medicine study and found a 35% increased risk of anxiety disorders after COVID-19, or 11 additional cases per 1,000 people after one year compared to those without COVID-19. The risk for depression was slightly higher.

When researchers compared people who’d had COVID-19 versus the flu, the risk of mental health disorders was again significantly higher with COVID-19.

“Mental health is closely tied to cardiovascular health,” Singh said. If somebody is anxious or depressed, “they’re not going to exercise that much. They’re not going to watch their diet, take control of their hypertension and other risk factors, their sleep is affected which can impact cardiovascular health, and so on.”

He said many COVID-19 survivors also have unresolved pain, grief and post-traumatic stress disorder, which can contribute to a decline in mental health.


At Biller’s post-COVID clinic, patients often describe experiencing “crushing” fatigue. Fatigue was the most common post-COVID symptom reported in a review of several studies published in August in Scientific Reports.

What you can do

Even though the long-term risks from having COVID-19 may be real, Singh said, they should not cause most people to be terribly worried. Instead, he said, it’s a good time to be proactive:

  • Take care of yourself. “A lot of my family and friends have gotten COVID earlier this year and last year,” Singh said. “What I’m telling them is just to be a bit more vigilant when it comes to their cardiovascular health and making sure their cardiovascular risk factors are well-controlled. Obviously, if one is having chest pain, shortness of breath or palpitations, that should not be ignored.”
  • Symptoms lingering? See a doctor. “It can take anywhere from two to six weeks to completely bounce back from the infection,” Singh said. But if people have persistent physical and mental symptoms beyond four to six weeks, “it’s wise to get checked out.”
  • Pay attention to sleep. Sleep disorders – which are linked to heart problems – can develop after COVID-19, research shows. “The importance of good sleep cannot be overemphasized,” Singh said. If you’re having trouble, you might need to see a specialist.
  • Stay informed. As research continues to untangle the mysteries of COVID-19, people will need trustworthy information. The Centers for Disease Control and Prevention offers regular updates about the coronavirus, and the National Library of Medicine provides a tutorial for evaluating health information.
  • Get vaccinated. COVID-19 vaccines reduce the risk of infection and severe illness. And while it’s not yet clear whether vaccination influences long-term symptoms in people who get breakthrough infections, Biller said, “prevention is the key.”

Source: American Heart Association