What’s up with statins and cognition, multiple sclerosis, and neurological waste management?

Pull up a chair ‘cause it’s that time of the week again.

A lot’s happened in the world of Neuro while you were busy planning the perfect Thanksgiving Day menu. At least, that’s what you’re telling everyone you were doing when really you were checking out who has the best Black Friday deals – yeah, we said it.

From findings that may lead to delayed progression of multiple sclerosis, to the latest in anti-aging medicine, to the answer you’ve been waiting for on what’s been going on with Statins, we’ve got you covered. So, keep reading to get all your turkey updates… errrr Neuro updates. Sorry, we’ve got turkey on the brain – pun totally intended.

Neuro Flashback

In 1998—just 21 years ago—Peter S. Eriksson, MD, PhD, Swedish stem cell neuroscientist (at the time with the Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA), and colleagues demonstrated that the human hippocampus retains its ability to generate neurons throughout life— neurogenesis—overturning 100 years of neurological doctrine. Dr. Eriksson used immunofluorescent labeling for bromodeoxyuridine and other neuronal markers to demonstrate that new neurons were generated from progenitor cells in the dentate gyrus of adults. And poof, just like that—mind blown. Proof that new brain cells are created throughout our lives was a seminal discovery in neuroscience.

In the News

Waste not, want not. Your brain may be conducting waste management while you sleep. Researchers discovered—for the first time—that during sleep, cerebrospinal fluid (CSF) washes in and out of the brain in waves and actually helps the brain clear out its “metabolic trash.” Using EEG caps and MRI machines, the team tracked electrical activity in the brains of 13 subjects. Their equipment revealed that during sleep, CSF seemed to synchronize with brainwaves to remove waste, including toxic proteins that could build up and block neuronal pathways. The rationale behind this—they think—is that during sleep, neurons are switched off and require less oxygen. This leads to less blood in the brain and dropping pressures. To maintain normal pressure, CSF levels must increase. Their results have implications for conditions like Alzheimer disease, where the buildup of protein plaques causes memory loss and cognitive impairment, possibly because of less efficient waste management. In the aging brain, this built-in waste management system may be compromised as well due to characteristically fewer slow waves, reduced circulation, and reduced CSF pulses.

Weekly Trivia

What neurodegenerative disease can be caused by cannibalism? The answer is kuru. Like mad cow disease, kuru is a prion disease, and was first discovered in the members of the Fore tribe of Papua New Guinea, which practiced ritualistic cannibalism. The cause? Eating brain matter of any kind can result in prion ingestion. With an incredibly long incubation period (up to 20 years or more), kuru causes trembling, weakness, headache, and limb pain, which progresses to uncontrollable jerking and laughing, difficulty swallowing, and loss of all muscle control. There is no known treatment for kuru, and death usually occurs within 1 year of symptom onset. Luckily, members of the Fore tribe realized this, and have modified their lifestyle so that kuru has nearly disappeared. Just some food for thought.

Novel Diagnostics

The Tesla of MRIs. Researchers from Brigham and Women’s Hospital have discovered that the powerful 7-Tesla (7T) MRI, instead of conventional MRI, can easily pick up a proposed marker of brain inflammation—leptomeningeal enhancement (LME)—in patients with MS. LME is more common in these patients and is also associated with gray matter lesions. Increased immune system activity on the meningeal surface has been linked to MS and its progression.

So, in comparing 30 participants with relapsing remitting MS with 15 healthy controls, researchers found that two-thirds of those with MS had LME, compared with only 6.7% of healthy controls. This added up to a whopping ten-fold increase. Plus, they saw a four-to-five-fold increase in cortical and thalamic lesions, which are unwelcome markers of gray matter injury that occur in MS and could play a role in disease progression. With these new markers of progression, it’s hoped that new treatments to stop the progression can be developed.

Tracking Alzheimer’s. Monitoring patients with Alzheimer disease (AD) just got easier thanks to a newly developed staging system that monitors ß-amyloid accumulations. Using fluorine 18-labeled florbetapir PET, this four-level staging system puts together a bunch of handy data from cerebrospinal fluid and PET scans. With this, researchers found that ß-amyloid stages were distinctly associated with CSF tau biomarkers, atrophy, and cognitive decline. And they could also analyze transitions between stages, and associated with specific gene expression profiles. Very useful!

Doctor, what’s the prognosis? No, it’s not a crystal ball, but the CaRdiac Arrest Survival Score (CRASS) may accurately predict outcomes in both survival and neurological function. In patients hospitalized for out-of-hospital cardiac arrest, bad survival and neurological outcomes occur because of age, presumable trauma, mechanical CPR, experiencing the event at a nursing home, hospital admission with ongoing CPR, and administration of adrenalin. On the other hand, better survival and better neurological function occur when certain conditions are presents: When patients have minor disease, receive amiodarone, have the event at work, school, or a doctor’s office, are normotensive, and received less than 5 minutes of CPR.

Novel Treatments

Beyond bipolar. Could lithium be a wonder drug? This seems the case in light of new findings that that it may reverse the damage that children might sustain after undergoing radiotherapy for a brain tumor. Because survival in children with brain tumors has improved greatly, many of them live—as adults—with memory and learning deficiencies caused by radiotherapy. In a preclinical study, researchers at the Karolinska Institutet showed that the memory capacity and learning capabilities of lithium-treated irradiated mice got better. Mice had brain irradiation in their early years, and then treated with lithium from adolescence until young adulthood. And voila! They performed just as well on cognitive tests as mice that had not undergone radiation. And, in a little more bang for the buck, researchers also saw increased new neuronal growth in the hippocampus during lithium treatment.

The old block and pass? Blocking the activated leukocyte cell adhesion molecule (ALCAM) may delay progression of multiple sclerosis (MS), according to Canadian researchers. In their study published in Science Translational Medicine, they identified ALCAM in both in vitro human and in vivo mouse studies. ALCAM is expressed by B cells—the bad guys in the progressive phase of MS—and controls their entry into the brain through blood vessels, allowing B cells to cross the blood—brain barrier. Lo and behold, blocking ALCAM in mice reduced the flow of B cells to the brain and slowed MS progression. ALCAM is also a potential villain in humans with MS, in whom it’s overexpressed.

Newest secret to not aging. It’s not romantic or even somewhat sexy…but…gut microbes could be the next frontier in the battle against aging. Researchers from Nanyang Technological University, Singapore, transplanted gut microbes from old mice (24 months) into young, germ-free mice (6 weeks old). At 8 weeks, the young mice demonstrated increased intestinal growth and neurogenesis. This uptick in neurogenesis was caused by enrichment of gut microbes that produce butyrate, a specific short-chain fatty acid. What’s more, giving the young mice just butyrate also had the same effects in increasing neurogenesis. Just a brief note: Butyrate is the result of the microbial fermentation of dietary fibers in the lower intestinal tract. It stimulates the production of FGF21, a pro-longevity hormone vital to the body for energy and metabolism. These results could lead to new food-based treatments for aging. So, while eating your way to a youthful glow doesn’t sound like a bad gig, don’t skip the moisturizer just yet!

Epilepsy? Bring on the CBD. Cannabidiol may reduce the frequency of seizures in patients with Lennox-Gastaut syndrome. Researchers studied the effect of doses of 20 mg/kg/d of cannabidiol with clinical trial simulations in patients taking 10- or 20-mg doses of clobazam. Elevated serum levels of clobazam and reductions in the incidence of drop-seizure frequency occurred, and they concluded that these effects were due to the drug-drug interaction between cannabidiol and clobazam. Their results may have important implications for the use of cannabidiol in this patient population. For those patients who are just a little too excited, you can tell them to rest easy because CBD isn’t actually cannabis.

New in Patient Management

Read. Write. And then read some more. Illiteracy may be tied to dementia, according to a study published online in Neurology. People who are illiterate have nearly a three-times greater risk of developing dementia compared with those who are literate. Surprised? You might not be if you consider that both reading and writing are activities that use the mind. Just think of all the neurons firing while you read the newspaper, do a crossword, or help your kids with their homework—or even (gulp!) complete your paperwork. In this study, 983 people (mean age: 77 years) who attended school for 4 years or less were divided according to their literacy. At baseline, 35% of those who were illiterate had dementia, compared with 18% of those who were literate. After a mean follow-up of 4 years, these percentages increased to 48% and 27% respectively. Even after controlling for cardiovascular disease, age, and socioeconomic status, researchers found that those who could not read or write were twice as likely to develop dementia during the study. Moral of the study: reading and writing may give you a lifelong advantage in the fight against dementia.

Mind-altering meditation? In results published in Brain Sciences, researchers found that a single session of guided meditation altered brain activity in those who don’t meditate. Meditation that focuses your awareness on your feelings, thoughts, and sensations as they unfold is called open monitoring meditation. Researchers tested it in 200 participants to determine whether it affected how people detect and respond to errors. After a 20-minute meditation exercise, they used EEG to monitor participants during a computerized distraction test. In those who meditated, the strength of the neural signal linked to conscious error recognition was increased compared with those who did not. Thus, meditation may help you become less prone to making mistakes. Ommmmm. Next up, researchers plan to study different forms of meditation and whether changes in brain activity could become behavioral changes with long-term practice. So the next time your friends try to invite you out on a Sunday afternoon, you can just respond: Namaste at home and meditate.

Statins cleared of a bad rap. Isolated case reports of cognitive decline in statin users have caused some to discontinue their medication. But—in a long-awaited study led by researchers at the University of New South Wales Sydney—statin use was not associated with memory loss and found to perhaps even be protective against it in some people at risk for dementia. Results were published in the Journal of the American College of Cardiology. Over 1,000 elderly people were studied over 6 years and tested in five areas of cognition with 13 different tests and MRI scans. There were no differences in changes in memory and cognition between statin users and non-users. Even better was the finding that in those with risks for dementia—such as heart disease and diabetes—statin use slowed cognitive decline. Hurrah for statins!

Speak up, I can’t hear you. We’ll say this one loud and clear: Hearing loss can make dementia worse. According to Colin Driscoll, MD, head and neck surgeon at the Mayo Clinic, hearing loss causes people to expend more of their cognitive abilities to simply understand the words that are being said and understand the sentences they form. Because all of their cognitive energy is spent on trying to hear, listen to, and understand speech, there is little available for other activities. According to Dr. Driscoll, while hearing loss does not cause dementia or Alzheimer disease, it can cause changes in cognitive abilities. The good news is, hearing loss can be improved with hearing aids and cochlear implants. It’s kind of intuitive (no?) that better hearing leads to better cognition, and less chances for social isolation and depression. Makes you think twice on what you should expend that cognitive energy listening to, though, right? Here are 5 podcasts worth listening to if you’re a doctor.

Latest in peer-reviewed studies

Kids with early onset or recurrent febrile seizures may need more help in school.

Statins decrease risks in young adults with ischemic stroke.

ODYSSEY study shows alirocumab decreases stroke risks.

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Upcoming Medical Meetings

2019 Advances in the Management of Epilepsy, in New Orleans, LA, December 6, 2019

31st Annual Pan Philadelphia Neurosurgery Conference, in Philadelphia, PA, December 6, 2019

American Epilepsy Society (AES) 2019 Annual Meeting, Baltimore, MD, December 6-10, 2019

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