Controversy around Biogen’s novel Alzheimer’s treatment. Plus, a surprising verdict for cannabis and pain control, and a new cancer drug pulls double duty for MS patients

With medicinal cannabis earning legalization in several states and across the United States, research gaps are beginning to close. But this week, we’re bringing bad news for proponents of cannabinoids as analgesics. You’ll also find research pointing to racial disparities in dementia diagnoses, a simple supplement that may improve age-related defects, research into a cancer treatment for multiple sclerosis, and more.

Neuro Flashback

Globally, Parkinson’s disease is the most common movement disorder and the second most common neurodegenerative disorder among the elderly. The first clinical description of the disease was written 2 centuries ago by the London surgeon/apothecary James Parkinson (1755-1824). But his 66-page booklet, titled An Essay on the Shaking Palsy, was not fully recognized during his lifetime. Parkinson, who lived through the American Revolution, the French Revolution, and the Napoleonic Wars, engaged in political activism, medical writing, amateur chemistry, paleontology, and spent time as a parish doctor and as a psychiatric physician. While he’s best known posthumously for his work on the disease that bears his name, it was paleontology that brought Parkinson fame during his lifetime—he was a founding member of the Geological Society of London. In recognition of his contribution to the nascent field of paleontology, his name was given to many fossils, particularly ammonites (eg, Nautilus parkinsoni). 

In the News

FDA poised to reject Biogen’s Alzheimer’s drug. In the next few months, the FDA will make one of its most important calls in recent memory: the rejection or approval of aducanumab, a first-of-its-kind treatment for Alzheimer’s disease, the merit of which has been fiercely debated during the past few years. Our advice? Don’t get your hopes up: FDA advisers recently reasserted their case against the drug over a purported lack of evidence for its efficacy

Aducanumab was designed to slow cognitive decline by targeting the cause of the disease, which differentiates it from other Alzheimer’s treatments that typically aim to alleviate symptoms. The FDA advisers who doubt its efficacy cited two clinical trials that produced opposite findings. One found that patients who received a high dose of aducanumab over a long period performed significantly better on a cognitive test than those who received placebo. The other study found that the drug had the opposite effect. The FDA, which is not required to follow the recommendations of its advisers (but typically does), is due to reach its verdict by early June. There’s still a path to approval, but this announcement makes it a narrow one.

The “breast” way to increase child IQ. All parents want to give their child a head start in life. According to a new study, one way to improve the odds that children get a cognitive boost is to ensure they’re getting mother’s milk. The new study found that the act of breastfeeding, as well as its duration, is associated with a lower risk of having a low IQ at the age of 5 years.

The study, published in Obstetrics and Gynecology, involved a secondary analysis of two parallel multicenter, double-blinded, randomized controlled trials in which candidates with a singleton pregnancy and either subclinical hypothyroidism or hypothyroxinemia were treated with thyroxine or placebo. Researchers looked at the self-reported breastfeeding of the 614 participants. They found that by age 5 years, children who had been breastfed tended to have a higher IQ than those who hadn’t; likewise, low IQ scores were less frequent with any breastfeeding vs no breastfeeding. Additionally, each additional month of breastfeeding was linked with a lower likelihood of having a low IQ score. Add this to the evidence that suggests “breast is best” for newborns.

Mimicking muscle stress signals can slow brain aging. When we age, our bodies undergo neurodegeneration in the central nervous system. Prior observations have indicated that our skeletal muscles influence CNS aging, but the underlying muscle-to-brain signaling mechanism remains unclear. Now, a new study has filled this gap, showing that mimicking the stress signals from muscles can help protect the brain and retina from aging by preventing the buildup of misfolded protein aggregates. The findings indicate that tailoring this signaling could help combat neurodegenerative conditions like age-related dementia and Alzheimer’s disease.

The study, published in Cell Metabolism, used fruit fly models and brain cell models called organoids. Researchers focused on muscle signals, which they found rely on an enzyme called amyrel amylase. Mimicking the stress-induced amyrel upregulation in muscles reduced the age-related accumulation of poly-ubiquitinated proteins in the brain and retina via chaperones. They concluded that proteasome stress in skeletal muscle hinders retinal and brain aging by mounting an adaptive response via amylase/maltose. The findings point to a possible new therapeutic approach for dementia and other age-related diseases.

Stress can lead to a “broken heart.” Takotsubo syndrome (TTS), also known as “broken heart” syndrome, is a rare and sometimes fatal heart condition, characterized by a sudden temporary weakening of the heart muscles that causes the left ventricle of the heart to balloon out at the bottom while the neck remains narrow. A new study has found that heightened activity in the brain, caused by stressful events, is linked to the risk of developing this rare condition.

The study, published in the European Heart Journal, analyzed data on 104 people with an average age of 68 years, and used brain scans with F-fluorodeoxyglucose PET-CT to assess brain activity prior to the development of TTS. Researchers found that the greater the activity in nerve cells in the amygdala region of the brain, the more likely patients were to develop TTS. The amygdala controls emotions, motivation, learning and memory, but it’s also involved in the control of the autonomic nervous system and regulation of heart function. The findings suggest that interventions to lower this stress-related brain activity could help to reduce the risk of developing TTS.

Neuro Trivia

Question: How many different types of brain cancer are there?

 

Answer: More than 150 different kinds of brain cancer have been documented.

Novel Diagnostics

Racial disparities found in dementia diagnoses. Racial bias has long plagued medicine and healthcare. A new study confirms that despite our aspirations, it remains a common problem in the field. The findings showed that Asian, Black, and Hispanic California Medicare fee-for-service beneficiaries are less likely than White beneficiaries to receive a diagnosis of incident mild cognitive impairment vs dementia.

The study, published in JAMA Neurology, looked at a cohort of 10,472 beneficiaries who had no diagnoses of dementia or mild cognitive impairment in 2013-2014. Researchers found that when compared with White beneficiaries, those who identified as Asian, Black, or Hispanic were less likely to receive a timely diagnosis of incident mild cognitive impairment vs dementia. Additionally, researchers observed that Asian beneficiaries were less likely to receive key elements of a diagnostic evaluation compared with White beneficiaries. They concluded that racial/ethnic minority groups have a lower likelihood of early diagnosis of dementia and comprehensive diagnostic workup when compared to White people, which highlights another key area of health disparities needing public health interventions.

Range of factors linked to newborn mortality. A new study aimed to explore the risk factors for mortality and neurodevelopmental impairment (NDI) among extremely premature infants, which had remained unclear until now. Researchers found that intrauterine growth retardation, bradycardia, periventricular hemorrhagic infarction (PVHI), necrotizing enterocolitis, and tension pneumothorax were all linked to neonatal mortality among infants born at 22 to 23 weeks’ gestation.

The study, published in Neonatology, involved a cohort of 104 infants delivered at 22 to 23 weeks’ gestation from 2006-2015. Researchers compared 65 and 34 cases of survival-to-discharge and postnatal in-hospital death, respectively, and 26 and 35 cases with and without NDI, respectively. They found that the survival rate was 75.0% and 62.0% among the infants born at 22 and 23 weeks’ gestation, respectively. The infants who died tended to weigh less and their intrauterine growth retardation rate was higher. Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring, periventricular hemorrhagic infarction, necrotizing enterocolitis, and tension pneumothorax.

Retina damage signposts stroke risks. When it comes to microvascular diseases of the brain, there are currently no screening tools for preclinical risk stratification. But new research appears to have found an early warning sign. The study indicates that damage to the retina may provide an early warning sign of increased risk for stroke and dementia and early death, providing time for early intervention.

The study used a cohort of more than 5,500 adults (mean age: 56 years), 13% of whom had retinopathy and 87% of whom had no evidence of retinopathy. Those with retinopathy were more likely to have vascular risk factors including hypertension, diabetes, dyslipidemia, heart disease, and chronic kidney disease. Additionally, they found that retinopathy was associated with a significantly increased risk of dementia and a nonsignificant increase in stroke risk, and that those with retinopathy were more likely to die within the next 10 years. The findings suggest that retina damage could serve as a tissue biomarker for cerebrovascular and neurodegenerative diseases.

Too few stroke patients screened with CTP. According to a new study, the availability and utilization of computed tomography perfusion (CTP) in patients with acute ischemic stroke (AIS) is low, and most patients are evaluated at non-CTP-performing hospitals. The findings indicate the need for alternative means of screening for AIS recanalization therapies.

The study, published in Circulation: Cardiovascular Quality and Outcomes, used data on AIS cases recorded between 2014-2017. Researchers examined the utilization of imaging in AIS cases and the change in utilization over time. Among 50,797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with MRI. Researchers noted that CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access. They concluded that CTP utilization in patients with AIS is low, and most patients were evaluated at non-CTP-performing hospitals.

Novel Treatments

Existing cancer drug may be effective for MS. The extracellular matrix plays a vital role in initiating various biochemical and tissue-specific signaling cascades. In the brain, this includes regulating the repair of myelin. In MS patients, however, this process fails, which has led researchers to consider the role of the extracellular matrix as a key variable in MS that can determine whether or not remyelination will occur after it has been damaged. Now, new research has revealed how regeneration of myelin in multiple sclerosis fails and suggests that an existing drug—currently being studied as a cancer therapy—can alter key signaling cascades that result in MS.

The research, published in the Journal of Neuroscience and in Nature Communications, examined mouse models of MS and focused on the key enzymes involved in the regulation of heparan sulfation, which plays a key role in signaling between cells and is involved in both the repair of myelin and the biology of oligodendrocyte progenitor cells (OPCs), the cells that generate myelin. Researchers found that SULF2, one of the enzymes involved in regulating heparan sulfation, is highly expressed by OPCs. In MS patients, this enzyme is found at high levels in regions of demyelination. Additionally, they found that a pharmacological agent called PI-88 (which is currently in clinical trials as an agent against various cancers) blocks SULF2 and can help speed up the recruitment of OPCs into regions of demyelination and promote the regeneration of new oligodendrocytes and myelin.

Depletion of microglia could treat blocked arteries. It’s long been known that reactive microglia, which are key immunocompetent cells, play an important role in the development of ischemic stroke. But the role of activated microglia in the development of ischemia has remained unclear. Now, however, the findings of a new study indicate that modulation of the inflammatory response via microglia elimination at a specific time point could be an encouraging therapeutic approach for the treatment of cerebral ischemia.

The study, published in the Journal of Neuroinflammation, used a Rose Bengal photothrombosis model to induce targeted ischemic stroke in mice. Researchers then eliminated resident microglia through intragastric administration of tamoxifen and intraperitoneal injection of diphtheria toxin. They found that the mice showed a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke. The findings indicate that the method could be a promising therapeutic approach for the treatment of cerebral ischemia.

Alzheimer’s drugs demonstrate long-term effects. Cholinesterase inhibitors are often recommended for the treatment of Alzheimer’s disease, but their long-term effects on cognitive function have remained the subject of debate. Now, a new study has found that cholinesterase inhibitors can result in persisting cognitive benefits and reduced mortality for up to 5 years after diagnosis.

The study, published in Neurology, looked at three drugs that are used in the treatment of Alzheimer’s disease: galantamine, donepezil, and rivastigmine. Using data on 11,652 patients treated with cholinesterase inhibitors and a matched control group of 5,826 untreated patients, researchers looked at cognitive function and mortality over a 5-year period. They found that those treated with cholinesterase inhibitors exhibited slower cognitive decline and 27% lower mortality vs the control group. The findings indicate that, of all three drugs, galantamine had the strongest effect on cognition.

Study shows drug can stop migraines before they start. Galcanezumab, a monoclonal antibody that binds calcitonin gene-related peptide (CGRP), has been shown to have early onset of effect in patients with migraine, but it was unknown whether the drug works for those who haven’t responded to other migraine preventatives. Now, a new study has demonstrated that galcanezumab showed efficacy, beginning the day after treatment initiation, in patients who had not previously benefited from migraine preventive treatments.

The study, published in The Journal of Headache and Pain, looked at 462 patients with episodic or chronic migraine who had two to four migraine preventive medication category failures in the past 10 years. Half were given galcanezumab at 120 mg per month and half were given a placebo. Researchers found that galcanezumab-treated patients had a significantly greater reduction in monthly migraine headache days over all 3 months of the study, when compared to placebo. The day after treatment began, only 28.4% of those on galcanezumab experienced a headache, compared with 39.2% of those on a placebo. 

New in Patient Management

Analgesic cannabis hopes go up in smoke. The medicinal use of cannabis as a painkiller has been getting a lot of attention in recent years, but the findings of a new study may throw some doubt into the debate. A newly published series of articles challenges the consensus over the effectiveness and safety of cannabis-based medicine for treating chronic pain.

The reviews, published in Pain, analyzed existing data on cannabinoids, including for so-called “medicinal cannabis” and “medicinal cannabis extracts.” While there’s preclinical data supporting the hypothesis of cannabinoid analgesia, researchers found that the evidence doesn’t reach the threshold required for the International Association for the Study of Pain to endorse its general use for pain control. According to one of the researchers, the studies were of “poor quality” and the evidence “was of very low-certainty.” Researchers concluded that far more research into medicinal cannabis is needed.

Simple supplement may slow aging. As we age, our bodies experience increased levels of oxidative stress (OxS), mitochondrial dysfunction, elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia. But researchers have been looking at ways to slow some of these processes. Now, new research reveals that supplementation with GlyNAC—a combination of glycine and N-acetylcysteine as precursors of the natural antioxidant glutathione—could improve many age-associated defects in older humans to improve muscle strength and cognition, and promote healthy aging.

The new study, published in Clinical and Translational Medicine, built off previous research which showed that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice resulted in mitochondrial dysfunction, and that supplementing GlyNAC in aged mice improved naturally occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. For the new study, researchers gave GlyNAC supplementation to eight older adults and eight young adults, and monitored their health over the course of 36 weeks. They found that the supplement lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin‐resistance, endothelial dysfunction, and genomic‐damage, and improved strength, gait‐speed, cognition, and body composition. The findings suggest that GlyNAC could be a viable method for promoting health.

Running from headaches. Migraines are notoriously difficult to treat, but a new study may have found a simple activity that can help patients. The study showed that routine moderate‐vigorous exercise may be an essential adjunctive strategy for improving headache burden in patients eligible for migraine prophylaxis.

The study, published in Headache, looked at data on 94 participants who provided information related to exercise, clinical and demographic characteristics, and lifestyle behaviors. Researchers analyzed daily information on headaches and health behavior over at least 6 weeks using electronic questionnaires focused on the impact of self‐reported, moderate‐vigorous exercise at least three times per week, as well as headache frequency, intensity, and duration. They found that, among those who reported regular use of migraine prophylaxis, a report of moderate‐vigorous exercise at least three times per week was associated with 5.1 fewer headache days compared to those who reported lower levels of exercise. Among those not using migraine prophylaxis, however, only 0.4 fewer headache days per month were observed. The findings suggest that regular moderate‐vigorous exercise could serve as an adjunctive strategy for managing headache burden in patients using migraine prophylaxis.

Blood pressure trajectory linked to stroke outcomes. According to a past study, acute-phase systolic blood pressure (BP) trajectories are associated with subsequent clinical outcomes among patients with ischemic stroke. But researchers were still unclear on the exact nature of this relationship. Now, a new study suggests that patients with ischemic stroke who have a high-decreasing or low-stable systolic BP trajectory after discharge may have a lower risk of adverse clinical outcomes.

In the study, published in Hypertension, researchers analyzed data on a total of 3,479 patients with ischemic stroke using three BP measurements after hospital discharge. They identified discharge systolic BP trajectories using latent mixture modeling, and looked at data on mortality, major disability, recurrent stroke, and cardiovascular events 24 months after stroke onset. They found that those in the high-decreasing and low-stable trajectory groups had a decreased risk of the composite outcome of death or major disability. Patients in the low-stable trajectory group, on the other hand, had the lowest risk of recurrent stroke, cardiovascular events, and the composite outcome of death or cardiovascular events. 

Latest in Journal Summaries

Cognitive changes during the menopausal transition.

Metabolic syndrome and the risk of late-onset Alzheimer disease.

Prestroke physical activity and adverse health outcomes after stroke in the Atherosclerosis Risk in Communities Study.

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Upcoming Medical Meetings

The following meetings are scheduled to be entirely in-person:

PAINWeek Conference 2021. Las Vegas, NV. September 7-11, 2021.

2021 Congress of Neurological Surgeons (CNS) Annual Meeting. Austin, TX. October 16-20, 2021.

Neuroscience 2021: The Society for Neuroscience (SfN) Annual Meeting. Chicago, IL. November 13-17, 2021.

 

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