A breakthrough blood test for brain tumors, 10x sensitivity for Alzheimer’s detection, and how coffee can save your brain
Beating a neurological disease—especially the degenerative kind—comes down to getting ahead of it. This week, we’re getting a whole lot closer to that lofty goal thanks to two new tests—one for Alzheimer’s and one for Parkinson’s—that each boast tenfold increases in sensitivity. Plus, we’ve got new neurological benefits of coffee, a debunked link between cannabis and stroke, and so much more.
Where did strokes get their name? Hippocrates, the philosophical genius, father of medicine, and world famous oath enthusiast, first recognized strokes more than 2,400 years ago. At the time, he called them “apoplexy,” which means “struck down by violence” in Greek. It wasn’t until the mid-1600s that Johann Jakob Wepfer first discovered that people who died from apoplexy had bleeding in the brain. He also discovered that a blockage in one of the brain’s blood vessels could cause apoplexy. Fast forward to present day and we’re still unraveling the mysteries of strokes. While there’s no cure, we’ve learned a lot about their cause, prevention, risk, and treatment, and now, many patients have pretty good chances of survival.
In the News
A tenfold improvement in Alzheimer’s biomarker detection. Most improvements in medicine—even the “statistically significant” ones—happen through tiny increments. That doesn’t seem to be the case for a new method for detecting biomarkers for Alzheimer’s disease, which, according to scientists from Washington State University, is 10 times more sensitive than the blood testing technology we’re using today.
Here’s how it works. Last year, researchers created an artificial enzyme using a single-atom architecture, called a nanozyme, made of single iron atoms embedded in nitrogen-doped carbon nanotubes. They used the nanozyme to mimic the active site of a natural enzyme and to detect Alzheimer’s proteins at levels 10 times lower than commercially available tests like ELISA. It’s still early days for this method, but the possibilities are huge. Rather than diagnosing Alzheimer’s through symptoms (at which point severe brain damage has already occurred), doctors could pinpoint risk of the condition much earlier, and even take steps that could prevent or slow onset. Let’s hope it works.
Polar plunge for Alzheimer’s prevention? Scientists have been getting pretty creative in their search for new ways to treat and prevent Alzheimer’s disease. And amid a lack of conventional therapies for the condition, they’ve stumbled on an unconventional tactic that appears to help: Cold water swimming. Researchers have identified a “cold-shock” protein in the blood of regular winter swimmers at London’s Parliament Hill Lido, an unheated, open-air swimming pool open to the public year-round. The protein, called RBM3, has been shown to slow the onset of dementia and even repair some of the damage it causes in mice.
Researchers tested swimmers for RBM3 during the winters of 2016, 2017, and 2018, and found elevated levels of the protein in their blood when compared to control members of a Tai Chi club who practiced near the pool. Cold water immersion likely won’t end up being a viable dementia treatment, since chilling someone to the core has risks that far outweigh the benefits. The mission, rather, is to find a drug that can trigger higher levels of RBM3 production. This study moves the scientific community one step closer.
The neurological consequences of pollution. Forecasts from the Alzheimer’s Association suggest Alzheimer’s prevalence will nearly triple by 2050, with costs (which are currently around $750,000, according to a recent survey) increasing by about 360% in that time frame. That’s partly attributable to the fact that the nation is getting older. But it could also be traced back to increasing levels of air pollution, according to a new report published in The Lancet Planetary Health, which found that air pollution was significantly associated with an increased risk of hospital admissions for not just Alzheimer’s, but Parkinson’s disease and other dementias, too.
From diagnostic billing codes, researchers identified 1 million cases of Parkinson’s and 3.4 million cases of Alzheimer’s and related dementia in people aged 65 years or older. For each 5 μg/m3 increase in annual particulate matter (PM2.5) concentrations in the air, risk of hospitalization for Alzheimer’s and Parkinson’s disease increased by 13%. “For the aging American population, improving air quality to reduce PM2.5 concentrations to less than current national standards could yield substantial health benefits by reducing the burden of neurological disorders,” the authors wrote.
Worse COVID-19 infection means higher stroke risk. COVID-19 data keep pouring in. Previous research has shown that COVID-19 is linked to thromboembolic complications, possibly mediated by increased blood coagulability and inflammatory endothelial impairment. To solidify this link and to offer new insights into COVID-19 and stroke, researchers from Dresden, Germany, performed two studies: An observational, multicenter cohort study and a systematic review.
In the observational study of 165 patients hospitalized for COVID-19 (49.1% males with a median age of 67 years, of which 72.1% had severe or critical disease), the overall stroke rate was 4.2%. In the systematic review, researchers included two observational studies involving 741 pooled patients with COVID-19, and their overall stroke rate was 2.9%. They found that there was a fourfold increased risk of acute stroke in patients with severe disease vs those with non-severe disease, with no evidence of heterogeneity. The results align with many other study findings of COVID-19 and neurological disease: We need additional research and close clinical neurological monitoring of patients infected with COVID-19.
How often do people in the US die from stroke?
Every 40 seconds someone in the United States has a stroke, and every 4 minutes someone dies from stroke. In 2018, 1 in every 6 deaths from cardiovascular disease was due to stroke. In all, more than 795,000 people have a stroke each year in the US. About 610,000 of these are new strokes, and about 185,000 are in patients who’ve had a stroke before.
Tiny blood test, huge potential for the brain. Using an enhanced form of liquid biopsy, Researchers at Massachusetts General Hospital in Boston have successfully detected genetic mutations that promote the growth of the most common type of adult brain tumors. It’s a breakthrough in blood test development for brain tumors, they said, and it notches a tenfold improvement over any prior assay for TERT mutations in the blood for brain tumors.
By comparing blood samples from patients with gliomas with tumor biopsy tissues from the same patients, Mass General researchers found that their own novel digital droplet polymerase chain reaction (ddPCR) blood test could accurately detect and monitor two mutations of the gene TERT over time. The mutations, known as C228T and C250T, are known to promote cancer growth and are present in more than 60% of all gliomas and 80% of all high-grade gliomas—the most aggressive and life-threatening type. The test is easy to use, quick, and low cost, meaning it could be easily performed at most laboratories, researchers said. Next steps involve expanding the blood test to be able to differentiate between multiple types of tumors.
New factors influencing Parkinson’s pathogenesis and progression. Scientists believe they are on to something promising involving key brain cell type changes involving lipids, inflammation, and the development of Parkinson’s disease. In a new study published in the Proceedings of the National Academy of Sciences, researchers were able to demonstrate concurrent lipid changes in dopaminergic neurons and their neighboring brain glial cells, such as microglia and astrocytes, in Parkinson’s brains. Specifically, microglia and astrocytes showed abnormal patterns of intracellular lipid storage, which were significantly correlated with the accumulation of lipids within dopaminergic neurons—the most vulnerable brain cells to the disease process.
The work shows that microglia, which to a large extent control macrophage and immune functions in the brain, are overloaded with lipids in Parkinson’s disease. On the other hand, astrocytes that normally supply lipids for maintenance and growth, on average, are losing some of that lipid content. Meanwhile, neurons are accumulating lipids in an inverse linear fashion relative to the surrounding astrocytes. “These results support our lipid-inflammation hypothesis in the causation of Parkinson’s disease initiation and progression and may help us discover and develop new therapies by leaving behind conventional thinking about PD pathology, which to some extent has been limited to neurons and protein aggregates,” researchers wrote.
Caring is cool—and a good sign for the brain. A growing body of evidence suggests that severe apathy in older adults is an early sign of dementia. Now we can add a new study to the pile. This one comes from the University of California, San Francisco (with support from the National Institute on Aging). They recently published the first longitudinal study to show that apathy could indeed be one of the early visible symptoms of cognitive decline.
The research team followed more than 2,000 individuals aged 70 years or older for up to 9 years. All participants were free from a clinical diagnosis of dementia at baseline. Following initial evaluation, they were sorted into low, moderate, or severe apathy groups. At the end of the study’s follow-up period, researchers found that those in the severe apathy group were 80% more likely to develop dementia than those in the low apathy group were. Researchers cited neuroimaging studies that linked neurophysiological observations with symptoms of apathy, suggesting that it’s not just a psychological characteristic, but a condition likely caused by certain types of neurodegeneration. Apathy may signal dementia onset late in the game, but in a condition with such a dearth of therapies, every step forward counts.
Seeing the potential behind Cystatin C. Ever heard of Cys C? It’s a novel biomarker of neurodegenerative diseases like Alzheimer’s and dementia. But we can’t conclusively say it’s a biomarker of mild cognitive impairment, because a systematic review hasn’t been conducted. Until now, that is.
Researchers from the Department of Neurology at the All India Institute of Medical Sciences in New Delhi, India, conducted a comprehensive search of studies published between 1950 and 2020, finding a total of 12 studies with 2,433 patients with mild cognitive impairment and 1,034 controls. They found a strong association between increased levels of Cys C and the risk of mild cognitive impairment compared to controls. In a subgroup analysis, a significant association for the high level of Cys C with the risk of mild cognitive impairment was observed in Asian participants, but not in Caucasian participants. Still, researchers concluded that Cys C can be considered a predictor for the risk of cognitive impairment.
A schedule III drug for Parkinson’s disease. Ketamine has had a rollercoaster reputation: First as an animal tranquilizer, then as a party drug, and more recently as a treatment for treatment-resistant depression. Soon, we may be able to add another indication to the list: Parkinson’s disease. Pharmather, a company focused on the research and development of psychedelic pharmaceuticals, recently filed an application with the FDA to receive Orphan Drug Designation for ketamine for the treatment of levodopa-induced dyskinesia associated with Parkinson’s disease.
Ketamine is already approved and has a known safety profile, with previous clinical reports suggesting low doses are well tolerated and can improve pain and depression—two comorbidities in patients with Parkinson’s disease. Researchers are currently working to patent the results from preclinical data from five case studies, which showed that low-dose sub-anesthetic ketamine infusion can be tolerable, safe, and potentially of long-term benefit to reduce levodopa-induced dyskinesia, improve on time, and reduce depression. Orphan drug designation could help them streamline research, more of which is certainly needed.
Reviewing rimegepant. Headaches beware—the FDA has accepted the supplemental new drug application (sNDA) for rimegepant, a calcitonin gene-related peptide receptor agonist, for the preventive treatment of migraine. The sNDA is supported by data from a randomized, double-blind, placebo-controlled phase II/III study that assessed the drug’s efficacy and safety in adults who had migraines for at least 1 year and between 4 to 18 moderate to severe migraine attacks per month in the 3 months prior to enrollment.
Results of the trial showed that patients treated with rimegepant achieved a statistically significant reduction in monthly migraine days from baseline (–4.3 days vs –3.5 days with placebo). What’s more, researchers observed a reduction of 4.9 monthly migraine days among patients treated with rimegepant who were not on concomitant preventive treatment (like topiramate and amitriptyline), compared with a 3.7-day reduction in the placebo group. Keep an eye on this drug—the results are solid and the approval date is expected in the first half of 2021.
Microglia, autophagy, and multiple sclerosis. Most multiple sclerosis treatments work by dampening the inflammatory nature of the immune response that the disease causes. They can control acute flare-ups, but don’t do much to stop disease progression and neurodegeneration. Microglia, on the other hand, are immune cells that constantly scavenge the central nervous system for unwanted cell debris in a process that’s related to autophagy—the process by which cells clean out or recycle damaged components. Now, researchers are looking to microglia as the next potential therapeutic breakthrough that could one day achieve the holy grail of halting disease progression in multiple sclerosis.
Researchers had previously established a link between an autophagy-related protein called Atg7 and disease severity in mouse models of multiple sclerosis. In this study, they took a closer look at microglial Atg7. Deleting the Atg7 gene in T cells didn’t affect disease progression, but removing it in microglia damaged the cells’ ability to clear debris and led to persistent neuroinflammation that lacked the same recovery phase that was found in control mice. Microglia without Atg7 showed decreased debris uptake and degradation. With that in mind, researchers hypothesized that boosting microglial autophagy might have beneficial effects on multiple sclerosis. They chose trehalose, a sugar naturally found in plants and fungi that’s known to induce autophagy, and found that treating aged mice with the sugar 1 week before multiple sclerosis induction decreased myelin debris clearance by microglia and ameliorated the severity of multiple sclerosis. It’s both very good news and very early days for microglia, so stay tuned for more.
Nasal drug administration for MS passes the smell test. Researchers are looking to a new drug called VX-765 delivered via an uncommon method—intranasal administration—to be the next drug to effectively slow the progression of multiple sclerosis. In a preclinical model, researchers at the University of Alberta showed that delivering anti-inflammatory drugs to mice helped prevent damage to brain cells, effectively slowing disease progression in a disease that has no known cure.
Their hypothesis rests on the power of inflammasomes, which are molecules that are responsible for the activation of an inflammatory response in the body. In a degenerative disease like multiple sclerosis, inflammatory responses must be controlled, and so far, VX-765 is a strong candidate to make that happen. It works by inhibiting caspase-1, a component of inflammasomes that promotes harmful inflammation. In previous studies, researchers observed beneficial results by delivering insulin intranasally in other models of brain inflammation. Why not try that again? They did—using mouse models, they dissolved VX-765 in a fluid and injected the mixture into the nose. It was effective in preventing demyelination and axon injury and loss. If VX-765 makes it through human trials, patients can expect treatment to be much simpler, because they’ll need less of the drug since it has a quick delivery into the brain and doesn’t need to travel through the circulatory system.
New in Patient Management
Coffee and Parkinson’s. We humans turn to caffeine to help prepare us for many of life’s problems, and now increasing evidence suggests that caffeine consumption can lower the risk of neurodegenerative disease. So how about Parkinson’s disease? New research suggests caffeinated drinks like coffee may help protect people from Parkinson’s disease caused by mutations in the LRRK2 gene—one of the most common genetic causes of familial Parkinson’s.
A team of researchers at Massachusetts General Hospital investigated the association between Parkinson’s disease and coffee consumption in 368 people taking part in the LRRK2 Cohort consortium, an assembly of study participants with and without Parkinson’s disease who carry mutations in the LRRK2 gene. Among these participants were 188 patients with Parkinson’s (118 with LRRK2 mutation and 70 without) and 180 healthy controls (115 with LRRK2 mutation and 65 without). Results showed that blood concentration of caffeine was significantly lower in patients with Parkinson’s than in controls, especially among LRRK2 mutation carriers. Among those gene mutations, patients with Parkinson’s had a 76% lower concentration of caffeine in their blood than the healthy control group. Patients with a normal gene copy had a 31% lower concentration of caffeine in their blood compared to controls. We can’t yet definitively say that caffeine consumption lowers the risk of Parkinson’s disease, but keeping in mind all its other health benefits, it certainly doesn’t appear to hurt.
CVT outlook not looking so good. It might feel like cases of cerebral venous thrombosis (CVT) have been on the rise in the last decade, but scientists don’t go on feeling. They rely on data, like the fresh set from a new retrospective cohort study published in Neurology, where they used validated ICD codes to identify 5,567 new cases of CVT in the State Inpatients Databases of New York and Florida from 2006-2016.
The results? Annual age- and sex-standardized incidence of CVT in cases per 1 million population ranged from 13.9 to 20.2, but incidence varied significantly by sex, with women (20.3-26.9) having a higher incidence than men (6.8-18.8). Incidence varied by age/sex too, with women between the ages of 18 and 44 seeing a 24.0-32.6 incidence rate, and men of the same age group seeing 5.3-12.8. Black Americans (18.6-27.2) were more likely than White Americans (14.3-18.5) and Asian Americans (5.1-13.8) to have higher CVT incidence over the study period. Overall, incidence increased from 2006 to 2016, but most of the increase was driven by rising case counts in all age groups of men, women 45 to 64 years of age, and women ≥ 65 years of age, with incidence in women 18 to 44 years of age remaining unchanged. Now on to the next question: Is this increase the result of changing risk factors or improved detection? We’ll let you know when we find out.
Dementia, infections, and mortality. People with dementia are at high risk of many less-than-desirable health outcomes. But how do they handle infections of any kind? Does their condition put them at increased risk for worse outcomes and mortality? Researchers at the University of Copenhagen in Denmark set out to find out in a nationwide registry-based cohort study.
Follow-up took place on January 1, 2000, or the 65-year birthday and lasted until death, immigration, or December 31, 2015, whichever came first. Exposure was incident dementia and a first infection and outcome was all-cause mortality. Mortality rate ratios (MRR) were calculated using poisson regression in four exposure groups (dementia yes/no and infection yes/no), and also by sex, infection, site, and time since infection. In total, researchers followed 1,496,436 people over 12,739,135 person years and found that MRR in dementia/infection was 6.52 and was increased for infections of all sites. Increased mortality was found in both the short-term (30 days) and long-term (10 years). The bottom line? Increased mortality from infections in people with dementia suggests they’re a highly vulnerable group deserving of clinical attention.
Cannabis and stroke. A few case studies have pointed to a link between cannabis use and increased risk of ischemic stroke, but these don’t bring the firepower of larger scale studies. Plus, many scientists have suggested that the correlation disappears when other factors are taken into consideration. Now, a larger-scale study of 9,350 patients shines light on this little-known link—it found no independent association between recent cannabis use and the incidence of acute ischemic stroke.
Researchers performed a retrospective observational study using a medical records database and included all patients aged 18 years or older admitted from 2015 to 2017 who underwent urine toxicology testing on admission. Of the 9,350 patients included, 1,643 (18%) had a positive urine cannabis test. Unadjusted risk ratio showed a 50% decrease in risk of acute ischemic stroke among cannabis users, but the effect was lost after adjusting for age, race, ethnicity, sickle cell disease, dyslipidemia, hypertension, obesity, diabetes, cigarette smoking, atrial fibrillation, and other cardiac conditions. More studies with larger sample sizes are needed, but for now, this research supersedes the conclusions drawn from individual case studies.
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Upcoming Medical Meetings
The following meetings are entirely virtual:
Frontiers in Circadian Medicine. November 2, 2020.
10th Annual Traumatic Brain Injury Conference. November 2-4, 2020.
The following meeting will have an online and in-person component:
7th International Symposium on Collaterals to the Brain. November 3-5, 2020. Los Angeles, CA.