Coffee’s brain-saving effects, biomarkers for a tricky neuro disorder, and a new vaccine for a deadly brain infection
Over the past few months, most news outlets have been mainly focused on covering the COVID-19 pandemic. So, you might not have heard about some of the major new studies, treatments, and diagnostics to come out of the field of neuroscience. For example, did you know that researchers have just found that your daily dose of caffeine could protect you against a crippling neuro disease? Or that a new FDA-approved vaccine could save thousands of lives from a deadly brain infection? Or that a certain biomarker could help pinpoint patients with a notoriously hard-to-diagnose neuro disorder? Read this week’s NeuroBrief for the full details and other top stories.
Ever met someone who just couldn’t remember you—no matter how many times you’d met them before? Either they’re really bad with faces, or they might have prosopagnosia—aka face blindness. This odd neuro disorder was first discovered in the early 19th century, but the term “prosopagnosia” was coined about 75 years ago by German neurologist Joachim Bodamer. Face blindness is usually caused by damage to the social part of the brain that deals with facial perception and memory (the right fusiform gyrus), either from stroke, brain trauma, or neurodegenerative disorders. Some people with face blindness have trouble recognizing familiar faces, while others can’t recognize their own face. And some even have trouble making out animal faces and objects like cars. (Imagine trying to find your car in a crowded parking lot. Yikes.) So, how can you tell the difference between prosopagnosia and forgetfulness or other memory disorders like dementia? Your best bet is to use the Cambridge Face Memory test, which more accurately diagnoses prosopagnosia than the two other standard tests available, the Benton Facial Recognition Test and Warrington Recognition Memory of Faces. Sadly, there’s no cure for face blindness, but those affected can learn to use visual and verbal clues to make out a person.
In the News
Age matters: The alcohol-stroke link. Tossing back a few too many beers with friends on the weekend can cause you to sport a beer gut as you get older. A little unsightly, but nothing diet and exercise can’t fix. Tossing back too many beers (and shots and glasses of wine) over the decades can lead to a beer belly and stroke (and possibly death). Not so easy to fix. A new study shows that heavy drinkers who continue drinking into old age tend to have bigger waistlines and higher stroke risk than people who aren’t heavy drinkers. Sounds bad, right? It gets even worse: The study also showed that the age when you stop heavy drinking may have an important role in the risk of early death. Which age was it? Keep reading—you might be surprised.
Researchers wanted to understand the link between dangerous heavy drinking (“hazardous drinking”) over a person’s lifetime and how this habit can affect the heart, liver, and odds of early death. They looked at data from over 4,800 drinkers (59 to 83 years old) from the 2011-2012 Whitehall II Study survey. Heavy drinking was considered to be a score of 5 or more on the Alcohol Use Disorders Identification Test for Consumption. Based on each drinkers’ scores for every decade of life, the researchers separated them into different groups: never heavy drinker, former early heavy drinker (stopping before 50 years), former later heavy drinker (stopping after age 50), current heavy drinker, or consistent heavy drinker (heavy drinker at each decade of life). More than half of the drinkers were heavy drinkers at some point in their lives. People who drank more throughout their lives had bigger waistlines, and current heavy drinkers had higher blood pressure, higher fatty liver index scores, and higher stroke risk. What’s even more surprising is that people who stopped heavy drinking after age 50 actually had a higher risk of non–heart disease-related death, even compared with current heavy drinkers. It’s still unclear how alcohol increases stroke risk, but other researchers have suggested that drinking raises your blood pressure levels, so that’s a likely explanation. Bottom line: Avoiding heavy drinking or stopping heavy drinking early on could save your life.
Drink a cup o’ joe, save your brain? Coffee makes the world go round. It’s a literal life-saver. And now researchers have found another benefit to add to coffee’s repertoire: protection against Parkinson disease (PD). (Yes, you read that right. We’ll understand if you want to hit pause and run to the coffee machine to make a cup right now.) A new study shows that having more caffeine and blood urate levels can lower the risk of PD.
Previous studies have already shown that caffeine and urate have neuroprotective properties. So, researchers studied if this protection also applies to PD. To do this, they looked at data from 369 people with idiopathic PD and 197 controls from the Harvard Biomarkers Study (HBS), measuring urate from blood samples. Participants filled out a questionnaire at the start of the HBS, answering questions on how many caffeinated and decaffeinated coffee, tea, and sugar drinks (zero to six or more a day) they had in the last year. Researchers used the questionnaires to measure caffeine intake.
They found that idiopathic PD patients drank fewer caffeinated drinks than controls. And this matched up with their other finding: The more caffeine participants drank, the lower their odds of having PD. Even after adjusting for age, sex, BMI, and plasma urate, the results were the same. They also found that higher blood urate levels in males and females were linked to lower PD risk. But, the researchers warned that a recent study of a urate-elevating treatment did not help people with PD. So, even though this current study supports the link between PD and lower urate levels, the researchers don’t recommend treatment strategies focused on raising them. They also say they can’t recommend caffeine as a target for PD since it hasn’t been studied in a long-term PD trial. But, coffee- and tea-lovers can rejoice in knowing that it’s likely that their brew has PD-protective potential.
Hearing loss = brain changes. We all know that hearing loss and old age go hand-in-hand. But, did you know that hearing loss in old age could also affect your brain? As your hearing gets worse, your risk of cognitive decline goes up. No one knew the reason behind this, until recently. Neuroscientists discovered that gradual hearing loss actually causes some parts of the brain to change, which affects memory.
They looked at the brains of mice that showed signs of hereditary hearing loss—which is like age-related deafness in people—and studied the density of neurotransmitter receptors in the brain that are important for making memories. They also looked at how hearing loss affected memory storage in the hippocampus. What’d they find? In the hippocampus, gradual hearing loss damaged synaptic plasticity—the process that enables memory. Basically, gradual hearing loss caused constant changes in neurotransmitter receptor distribution and density, which messed up sensory information processing and stopped the hippocampus from working well. Bottom line: The worse your hearing loss, the worse your memory becomes.
So, what can you do to help your patients? Obviously, trying to prevent hearing loss in the first place is key. Some healthy lifestyle habits—like not smoking, keeping your heart in tip-top shape, and avoiding loud noises—can slow hearing loss as you age. But what about patients who are already showing signs of hearing loss? Good question. Unfortunately, there’s no good answer. Some studies have shown that hearing aids can help cut cognitive decline and dementia risk, but researchers aren’t sure how or why it works. It’s an area that needs more study.
Parkinson disease starts where? When you’re second-guessing yourself, people will tell you to go with the feeling in your gut. But not everything that starts in the gut is good. Indigestion, anyone? You know what else starts in the gut? Parkinson disease (PD)—at least that’s what one study shows. Researchers mapped out the types of cells responsible for different brain disorders. And one of the cool things they discovered was that cells from the gut’s nervous system played an important role in PD. This means that the disease might start in the gut. Their findings provide a “roadmap” that could lead to new treatments for neuro and psych disorders.
The researchers wanted to get a better understanding of the cell types affected in different brain disorders to understand the causes and, hopefully, create new treatments. So, they combined genetic data from mice and humans to map the cell types behind different brain disorders, including PD. They looked at differences in brain tissue from healthy people as well as people with PD at different disease stages. They found that dopaminergic neurons were linked to PD, which wasn’t surprising. (The death of dopaminergic neurons is a hallmark of PD and is believed to play a key role in PD development.) What was surprising was that enteric neurons (those in the gut) were also linked to PD. Another surprising thing they found was that oligodendrocytes (support cells in the brain) were affected early on, meaning that they might have an important role in the early stages of PD. The same evidence linking oligodendrocytes to PD was found in animal studies, bolstering the connection even more. Oligodendrocytes were also affected before dopaminergic neuron death. This makes oligodendrocytes an attractive new target for PD interventions.
How many neurons are in the average human brain?
This was a tricky one. And if you guessed “100 billion,” you were close, but no cigar. In med school, you were probably taught that the human brain has about 100 billion neurons—a number that’s been repeated over and over for decades. But, that’s not true. The magic number is actually closer to 86 billion. That’s what scientists discovered when they actually sat down, dissolved a human brain, and counted the nuclei of neurons to get a true tally of how many cells make up the brain. (On a side note, experts have also found that humans use 25% of their total energy to fuel all of these brain cells. Talk about brainpower.)
OSA severity tool for epilepsy patients. Do you know what the fourth most common chronic neuro disease is? It’s epilepsy. And obstructive sleep apnea (OSA) affects more people with epilepsy than those in the general population. What’s worse is that, in older folks with epilepsy, OSA can worsen seizure control. For clinicians, it can be hard to predict how bad OSA will be in patients with epilepsy because there aren’t many good screening tools on the market. Luckily, there’s a new instrument that might be able to help. Researchers have created the STOPBAG2 scoring instrument. It combines sleep-related symptoms and continuous variables for age and BMI, and can accurately predict all levels of OSA severity in adults with epilepsy. This is big news because it beats out previous versions of the scoring system: STOP (Snoring, Tiredness/sleepiness/fatigue, Observed apneas, high blood Pressure), STOPBANG (STOP, BMI ≥ 30kg/m, Age ≥ 50 years, Neck circumference ≥ 40 cm, and Male gender), and STOPBAG. The higher the score using the tools, the higher the risk of OSA.
Researchers tallied up scores for STOP, STOPBANG, STOPBAG, and STOPBAG2 in 133 adults with epilepsy who had polysomnography. They used the apnea-hypopnea index (AHI) to measure how bad OSA was in each person. They found that STOPBAG2 was much more sensitive than the other tools for predicting mild, moderate, and severe OSA. It was also more specific for predicting mild OSA, but its specificity was similar to the other tools for moderate and severe OSA. The key takeaway: STOPGBAG2 is the best predictive tool for OSA severity. The researchers say their findings on STOPBAG2 “[support] its implementation in epilepsy clinics.”
New risk score for multiple sclerosis. As you know, treating a disease is rarely a one-size-fits-all. With so many variables involved in treatment strategy, having the right tools for diagnosis and prognosis is incredibly important. The reality is that there aren’t that many great tools out there. And this is especially true for multiple sclerosis (MS), where info on the risk factors for progression is pretty much nonexistent. To help tackle this, a handful of researchers took matters into their own hands and came up with a new clinical risk score for predicting long-term MS progression, which they say can be easily applied in clinical practice.
To create the model for the score, the researchers used data from 288 patients with MS (derivation sample) to determine risk factors for progression. They then used another 144 patients with MS to validate the accuracy of the scoring system (validation sample). The risk factors that were found to be independently linked to long-term progression were: no specific MS treatment before Expanded Disability Status Scale 3, getting the disease after age 30, pyramidal and cerebellar impairment as the first disease symptoms, time between the first and second relapses less than 2 years, and African ancestry. One point was given to each risk factor identified, and the total number of points gave the overall risk score. A higher score meant that a patient had reached secondary MS progression.
The score was able to predict progression in the validation sample. This was proven by the fact that there were no major differences between the estimated and actual number of patients in progression. There were also no big differences seen between patients with low risk (≤ 2 points) and high risk (≥ 3 points) in the derivation sample vs the validation sample. Patients in the derivation sample with ≥ 3 points had a higher risk for progression. The researchers’ new findings and score are important since these prognostic factors can give clinicians better insight into the best treatment strategies for their patients in terms of efficacy and safety.
Predictive biomarkers for PN. One of the trickiest neuro disorders to diagnose and treat is peripheral neuropathy (PN). It’s common in the general population but hard to diagnose due to varied symptoms and affected body parts. And this difficulty is compounded in older folks, who are at even higher risk and often have overlapping symptoms with other medical problems. Researchers wanted to find out which biomarkers could be used to identify older people with PN and diabetes, which is a common cause of PN. Since there aren’t much data on the risk factors for PN, the researchers looked at how cardiac, kidney, inflammatory, and diabetes biomarkers were associated with PN in a community-based sample of older people. They carried out a cross-sectional analysis of data from over 3,000 people in the Atherosclerosis Risk in Communities (ARIC) study.
ARIC participants were older adults (71-94 years old) with and without diabetes who had monofilament PN testing done between 2016 and 2017. The participants also had data on measures of cardiac function (high-sensitivity cardiac troponin [hs-cTnT], N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β2-microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [HbA1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and C-reactive protein. The researchers used logistic regression to find out how each of these biomarkers was linked to PN after adjusting for traditional risk factors (age, race, sex, cardiovascular risk factors).
They found that 33.5% of the ARIC participants had PN, including 37.3% of those with diabetes and 31.9% of those without diabetes. Most participants with PN were older, male, and had higher BMI than those without PN. People with and without diabetes who had PN showed higher median levels of hs-cTnT. Those who did not have diabetes but had PN showed higher levels of NT-proBNP. And those with diabetes and PN had higher levels of hyperglycemia biomarkers: HbA1c, fructosamine, and glycated albumin. Although the researchers acknowledged that their findings on PN biomarkers weren’t perfect—pointing to their cross-sectional study design, lack of clinical neuropathy-related outcomes, and possible unaccounted-for confounders as limitations—their results do support hs-cTnT as a global marker of end organ damage, and could help identify people with PN.
A cure for chronic pain? Back in the day, docs would give opium to their patients for chronic pain relief and then call it a day. Sounds crazy, we know. But you have to remember that pain meds were still in their infancy and there weren’t a lot of options. Thankfully, times have changed, and medicine has come a long way since. But, we’re still way behind when it comes to safe and effective drugs for chronic pain. Current chronic pain meds don’t provide full relief and often come with a lot of harsh side effects like nausea, vomiting, constipation, lethargy, and even addiction. You’d think that, for a health problem that affects about 10% of the world, we’d have a better handle of treatment. Well, we’re getting there. Seeing the need for better treatment, researchers at the University of Copenhagen started working on a new drug for chronic pain about a decade ago. (Now, that’s commitment.) After recently testing their experimental compound on mice, the researchers say that it offers complete pain relief. The compound is actually a peptide called Tat-P4-(C5)2.
Other experimental treatments for chronic pain have generally worked by dampening nerve pathways. Turns out, because of the lack of specific targeting in the treatment, they usually have pretty bad side effects. Tat-P4-(C5)2, on the other hand, is targeted to only affect the nerve changes that cause pain. So, unlike other pain meds, it doesn’t seem to have any harsh side effects. Previous studies have shown that the peptide can also reduce addiction, so the researchers hope that it can help patients with chronic pain who’ve become addicted to opioid pain meds. Their next step is to start testing the compound on people, but their long-term plan is to establish a biotech company ASAP to help turn the compound into a drug.
A new meningitis vaccine on the horizon. The FDA has approved a Biologics License Application for Sanofi’s new quadrivalent meningococcal vaccine called MenQuadfi. (What a mouthful. Good luck remembering that one! ) It’s indicated for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W, and Y. (But, it does not prevent N. meningitidis serogroup B disease. Good thing there are already vaccines—Bexsero and Trumenba—available for that serogroup.)
Now, we know what you’re thinking: Aren’t there already vaccines that protect against N. meningitidis serogroups A, C, W, and Y? Yep, you’re absolutely right. The problem’s that existing meningococcal conjugate or MenACWY vaccines are only recommended for limited age groups. MCV4 vaccines (Menactra and Menveo) are indicated for use in people ages 55 and younger (as young as 2 months). There was a vaccine for people over age 55, MPSV4 (Menomune), but it was discontinued in 2017 due to “manufacturing challenges,” leaving high-risk older adults without any effective protection.
So, what does MenQuadfi bring to the table? It’s the first and only quadrivalent meningococcal vaccine in the United States that uses tetanus toxoid as a protein carrier (but it’s not a substitute for a routine tetanus shot by any means). But, more importantly, it’s indicated for use in patients ages 2 and up. MenQuadfi was proven to be safe and effective in 5 double-blind, randomized, multicenter phase 2 and 3 trials in about 5,000 patients aged 2 years and older. It was studied in people who never had meningococcal vaccination as well as in people who were previously immunized with a quadrivalent meningococcal vaccine. The most common side effects after getting a shot of MenQuadfi were injection site pain, myalgia, headache, and malaise. MenQuadfi is expected to be available in 2021. Its ready-to-use liquid formula (0.5 mL single-dose vials) will allow clinicians to avoid vaccine reconstitution.
New add-on med for PD “off episodes.” Levodopa is, arguably, the most potent first-line drug for Parkinson disease (PD). When patients with PD take levodopa, the brain converts the drug into active dopamine, which eases motor problems. The downside to this wonder drug is that, with long-term use, the beneficial effects wear off before new doses can be taken. Once levodopa stops working, an “off episode” can occur, where symptoms start cropping up again. There are drugs that can help manage PD “off episodes,” including both injections and oral tablets, but they usually come with harsh side effects (like dyskinesia) or are not as effective.
To help combat this, the FDA has approved once-daily oral Ongentys (opicapone, Neurocrine Biosciences) as add-on treatment to levodopa/carbidopa for patients with PD during “off” episodes. It’s taken as a once-daily oral capsule (25 mg or 50 mg) at bedtime. Ongentys stops levodopa from breaking down, making levodopa’s clinical effects last longer in patients with PD. It was approved based on data from 38 clinical trials, including 2 multinational, double-blind, phase 3, parallel-group studies in over 1,000 patients. Both phase 3 trials lasted 14-15 weeks each, and all participants were taking levodopa/DOPA decarboxylase inhibitors (alone or with other PD drugs). The most common side effects in the studies were constipation, increased blood creatine kinase, hypotension/syncope, and weight loss. Even though dyskinesia was also a reported side effect, the makers say that Ongentys “significantly reduce[s] ‘off’ time” and increases “on” time without “troublesome dyskinesia when taking levodopa/carbidopa.” Ongentys is expected to be available later this year.
New in Patient Management
An apple a day keeps Alzheimer away. Remember when you were a kid and your mom would tell you “an apple a day keeps the doctor away?” Turns out, mom is always right. A new study that shows people who eat a diet rich in flavonols—a type of antioxidant found in nearly all fruits and vegetables, plus tea and wine—may be at lower risk for Alzheimer disease (AD) dementia.
Researchers studied 921 older adults to find out how dietary flavonol intake and AD dementia are connected. Participants were dementia-free at the start of the study. They filled out a questionnaire each year, reporting how often they ate certain foods, and provided details on education, physical activity, and how much time they spent doing mentally engaging tasks. Participants were followed for an average of 6 years and were tested annually for AD dementia. During the study, 220 of them developed AD. The researchers found that participants with the highest flavonol intake were nearly 50% less likely to develop AD dementia later on in life vs those with the lowest level intake.
But, certain flavonols topped others. The researchers broke down flavonols into four types: isorhamnetin, (found mostly in pears, olive oil, wine, and tomato sauce), kaempferol (kale, beans, tea, spinach, and broccoli), myricetin (tea, wine, kale, oranges, and tomatoes), and quercetin (tomatoes, kale, apples, and tea). People with higher intakes of isorhamnetin or myricetin were each 38% less likely to develop AD dementia, but the risk was even lower in those who ate more kaempferol: 51%. Quercetin (not to be confused with quarantine) was not linked to lower AD dementia risk at all, though.
Even after adjusting for genetics, demographic, lifestyle factors, and risk factors for AD dementia—like diabetes, heart attack, stroke, and high blood pressure—the results were the same. Although the researchers note that their study does not prove a causal effect, they speculate that eating more flavonols may be a pretty cheap and easy way to fight dementia.
A simple strategy TBI blood clots. Chances are you’ve had a patient with traumatic brain injury (TBI) at some point in your career. It’s one of the leading causes of death and disability worldwide and affects about 2.8 million Americans each year. Because patients with TBI tend not to be as active, they’re prone to blood clots. But, emerging evidence shows that preventative, anti-clotting meds can be used safely in people with TBI (if the brain injury is stable). The problem is that these meds aren’t being used as often as they should in patients with TBI, according to benchmarking data. So, researchers wanted to see if a hospital-wide, preventative, anti-clotting protocol would work to improve outcomes in these patients. And, boy, did it!
The protocol included education, weekly audits, and adherence feedback in real-time. Researchers studied 681 patients with TBI. The protocol was used for 313 of these patients. After applying the protocol, a higher number of patients (81%) received anticoagulation compared with those who didn’t receive the protocol (39%). Protocol patients had also had fewer (2.2%) blood clots than non-protocol patients (5.5%). The researchers concluded that the protocol improved process measures and outcomes in patients with TBI. So, it seems that benchmarking data could actually help healthcare institutions spot clinical areas that need work in real-time, and quality improvement can benefit patient outcomes.
Stroke prevention for PFO. A lot of us probably have health problems we may not even know about. Just look at the coronavirus. So many people had the virus but showed no signs or symptoms. Patent foramen ovale (PFO)—a hole in the heart that didn’t close all the way after birth—is another common health problem that many people never know they have. About 25% of adults have a PFO. It usually doesn’t cause issues or need treatment, and it’s typically caught during tests for other medical conditions. But, for some people, PFOs can become extremely dangerous. Scuba divers and skydivers, for example, are at higher risk of stroke from PFO because of the sudden, extreme changes in air pressure they endure, which can trigger blood clots. When small blood clots pass through the hole, they can travel to the brain and cause a stroke. The American Academy of Neurology (AAN) recently issued new guidelines for docs caring for patients with stroke and PFO.
Originally published in 2016, the guidelines now recommend closing a PFO in some patients younger than 60 years old to prevent another stroke. The update comes on the heels of new evidence showing that, for people who suffered a stroke because of PFO, closure plus meds to prevent blood clots can lower the risk of future strokes better than meds alone. But, PFO closure isn’t recommended for patients with another higher-risk cause of stroke. For patients who don’t want to have surgery, the AAN recommends that docs prescribe antiplatelet drugs like aspirin or anticoagulant drugs like warfarin to prevent blood clots. The new guidance has been backed by many health organizations, including the top dogs: the American Heart Association, the American Stroke Association, and the European Academy of Neurology.
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Upcoming Medical Meetings
The following conferences have not yet been canceled. Please check the conference websites for up-to-the-minute information:
Update on Neurology and Psychiatry of Women – What Every Practitioner Needs to Know, in Boston, MA, May 16-17, 2020.
16th World Congress on Vascular Dementia and Neurodegenerative Diseases, in Osaka, Japan, May 18-19, 2020.
26th Annual Summit on Neuroscience & Neurological Disorders, in Osaka, Japan, May 18-19, 2020.
The following has been changed to a virtual workshop:
6th congress of the European Academy of Neurology (EAN 2020), in Paris, France, May 23-26, 2020.