Breakthrough Alzheimer’s study offers hope for early detection, LSD gets a moment in the sun, and novel treatments for PTSD
LSD could be on its way from the fringes to the pharmacy. This week, we’re bringing you a new study that has pinpointed the drug’s mechanisms, paving the way for treatment of certain psychiatric disorders. We also have news of how afternoon naps could protect against dementia, a neural network to screen for sleep apnea, upcoming trials designed to treat PTSD by erasing fear memories with a common drug, and more.
The first medical description of a stroke is credited to Hippocrates, who recognized the condition more than 2,400 years ago. Back then, it was known as “apoplexy,” which roughly translates to “struck down by violence,” due to the paralysis and changes in well-being that occur in stroke patients. It wasn’t until the mid-1600s that doctors noticed that patients with stroke had bleeding in the brain. That discovery is credited to Swiss pathologist Johann Jakob Wepfer, who also found that a blockage in one of the brain’s blood vessels could cause stroke.
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Exercise your brain by taking a good, old-fashioned nap. People who are prone to catnaps in the afternoon shouldn’t let anyone scold them for being lazy. After all, they can now say they’re sleeping for their cognitive health. According to a new study, a regular afternoon nap is linked to better mental agility.
The research, published in General Psychiatry, looked at a cohort of 2,214 healthy individuals aged 60 years or older. Of the total participants, 1,534 took a regular afternoon nap. All participants were then screened for dementia via a Mini Mental State Exam (MMSE), which measures cognitive ability and higher function, including visuo-spatial skills, working memory, attention span, problem-solving, locational awareness, and verbal fluency. Researchers found that nappers scored significantly higher on the MMSE cognitive performance tests. While this was an observational study with several limitations, researchers hypothesize that the extra sleep plays a mediator role in regulating the body’s immune response, as those with higher levels of inflammation tend to take more naps.
New database could illuminate how COVID-19 impacts neurology. It’s been established that COVID-19 can result in long-lasting damage to the brain, spinal cord, nerves, and muscles in some patients, but it’s far too soon for researchers to have a proper understanding of these effects. In a preemptive effort to speed up this process, NYU Langone Health created the COVID-19 Neuro Databank/Biobank (NeuroCOVID), which will collect information from clinicians about neurological symptoms, complications, and outcomes, as well as COVID-19 effects on pre-existing neurological conditions.
The database will be a resource of clinical information and biospecimens from patients of all ages who have experienced neurological problems associated with SARS-CoV-2 infection. Participating healthcare providers and clinics across the country have been encouraged to use a web-based data portal to submit de-identified information for the database, along with specimens collected during clinical procedures and tests. NYU Langone Health wants data on neurological symptoms, comorbidities, disease course, complications, sequelae, and outcomes. Researchers hope to use the database to examine how COVID-19 affects the nervous system, and how common—or rare—such complications are.
Human and primate brains might have had a similar upbringing. According to a new study, the evolutionary development of human and primate brains appear alike with regard to communication and memory functions. The study, published in Neuron, compared auditory cortex information from humans and primates and found significant links between the two. The team took brain imaging information obtained from neurosurgical patients being monitored for treatment and compared it to imaging results of monkeys undergoing stimulation of the auditory cortex.
The work highlighted a previously unknown brain pathway that humans and primates share, which could signify an evolutionary process dating back at least 25 million years. These findings are vital, as the mechanism for how brain stimulation works in patients with neurological and psychiatric disorders is not well-understood. According to researchers, the findings have already inspired future research into how brain stimulation might aid neurology and neurosurgery patients.
For protection, the brain listens to the gut. Researchers have long assumed that the main function of astrocytes, the most abundant type of cells within the central nervous system (CNS), is to provide nutrients for nerve cells in the brain. Research has also indicated that astrocytes can actively promote neurodegeneration, inflammation, and neurological diseases. However, a new study has shown that a specific subset of these cells do the opposite: they serve a protective, anti-inflammatory function within the brain based on signals regulated by the bacteria in the gut.
The study, published in Nature, used refined gene- and protein-analysis tools to identify the novel astrocyte subset, which resides close to the meninges and expresses a protein called LAMP1, along with a protein called TRAIL. These proteins can induce the death of other cells and help the LAMP1+TRAIL+ astrocytes limit CNS inflammation by inducing cell death in T-cells that promote inflammation. Researchers say this information was missed in prior studies, because they looked at astrocytes as though they all performed uniformly.
Has anyone ever sold their brain?
Yes, sort of. In 2003, an artist named Jonathon Keats began offering contracts for people to purchase up to 6 billion of his neurons upon his death. Investors paid $10 for a contract for 1 million neurons. When Keats dies, these investors will have the option to pay a final sum of $10,000 for their new neurons. The contracts could net close to $60 million. Some of the money will be used by Mr. Keats “to keep his brain functioning” while a holding company makes licensing deals for the brain.
Breakthrough Alzheimer’s study identifies first tau deposits. During the early stages of Alzheimer’s disease—when there are no diagnosable cognitive symptoms—the cerebral cortex is in a state of transient hyperexcitability. While several studies on animals have found that accumulations of tau and beta-amyloid proteins were associated with this increased excitability and brain dysfunction, no research had demonstrated this in humans. But a new study has spotlighted how the first deposits of tau proteins in the brainstem are associated with neurophysiological processes specific to the early stages of Alzheimer’s development.
Researchers from the GIGA Cyclotron Research Centre in vivo imaging laboratory at the University of Liège, Belgium, looked at whether the first deposits of tau and beta-amyloid proteins in the brains of healthy individuals, 50 to 70 years of age, could be linked to a higher level of cortical excitability. Researchers used multiple neuroimaging methodologies (eg, MRI, PET) to characterize the quantity of tau and beta-amyloid proteins in the regions where they first appear. The study also measured the excitability of each participant’s cortex using transcranial magnetic stimulation techniques, along with electroencephalographic recordings. The findings constitute the first in vivo observation in humans of the early link between proteins associated with Alzheimer’s disease and their impact on brain function—suggesting that the hyperexcitability of the cortex could be used as a biomarker.
AI tool could predict schizophrenia. There are roughly 3.5 million Americans with schizophrenia, a potentially debilitating condition that is difficult to diagnose and treat before troublesome symptoms emerge. Now, a new study lays out an interesting step forward for developing an artificial intelligence tool that can detect schizophrenia by analyzing brain scans.
The study, published in npj Schizophrenia, sought to test the AI tool, called “Ensemble algorithm with Multiple Parcellations for Schizophrenia prediction (EMPaSchiz).” The tool appeared to predict a schizophrenia diagnosis with 87% accuracy by examining patient brain scans. In the new study, it analyzed functional MRIs of 57 healthy first-degree relatives of patients with schizophrenia. Researchers found that it accurately identified the 14 individuals who scored highest on a self-reported schizotypal personality trait scale. The developers intend EMPaSchiz to be used as a decision-support tool, not as a replacement for diagnosis by a psychiatrist, however they hope it can be used to diagnose schizophrenia earlier. That could aid studies into the disease’s progression.
Concerned about sleep apnea? There’s a new neural network for that. According to some studies, up to 90% of stroke patients experience sleep apnea, which can reduce quality of life, impede? rehabilitation, and increase the risk for recurrent cerebrovascular events. Although screening for sleep apnea is recommended for patients with cerebrovascular disease, it’s rarely conducted on stroke survivors due to the high cost and time investments. Now, researchers have developed a neural network that can assess the severity of sleep apnea in patients with acute stroke and transient ischemic attack by using a simple nocturnal oxygen saturation signal.
For the study, published in Sleep Medicine, researchers used the apnea-hypopnea index, which represents the number of apnea and hypopnea events per hour. When they compared the results of traditional manual scoring and those using the new neural network, the median difference was only 1.45 events per hour. Plus, the neural network was found to be 78% accurate in classifying patients into four different categories of sleep apnea severity (no sleep apnea, mild, moderate, severe). According to researchers, the findings indicate that the neural network offers an easy and cost-effective way of screening for sleep apnea, which could result in early interventions to stop recurrent cerebrovascular events.
Study sets the lowest bar for amyloid-PET. One of the hallmarks of Alzheimer’s disease is a buildup of amyloid protein plaques in the brain. Now, with an eye toward earlier intervention for dementia patients, a new study has defined the lowest threshold for amyloid-PET to predict future cognitive decline and amyloid accumulation.
The study, published in Neurology, sought to redefine the β-amyloid (Aβ)-PET threshold based on the lowest point in a baseline distribution that could robustly predict future Aβ accumulation and cognitive decline. Researchers looked at 342 clinically normal participants from the Harvard Aging Brain Study, 157 from the Australian Imaging, Biomarker, and Lifestyle study of aging, and 356 from the Alzheimer’s Disease Neuroimaging Initiative. They analyzed sequential Aβ cutoffs to identify the lowest cutoff associated with future changes in cognition and Aβ-PET. Their findings suggest that, among clinically normal individuals, a specific Aβ-PET threshold can be predictive of cognitive decline. Having successfully established optimized thresholds, the researchers hope that the findings will inform future research and clinical trials targeting early Aβ.
To conquer PTSD, conjure and eradicate those fearsome memories. An upcoming clinical trial aims to test a new treatment known as a “recall and erase” strategy for PTSD. The trial, named ErasingFear, will involve exposing patients to fear memories and then giving them the beta-blocker drug propranolol, in the hope that it rids patients of these triggering memories. The trial, which is being led by Merel Kindt, PhD, professor at the University of Amsterdam, will use a cohort of arachnophobes who are exposed to fleet-footed spiders and tarantulas to provoke their fear memory.
The participants will then receive the propranolol, which hypothetically will interfere with the brain’s process of resaving and rewriting the same memory for long-term storage. As such, the strategy differs from cognitive behavioral therapy, where people are exposed to a fear cue and learn through direct experience that their fear is unrealistic. With propranolol, memories will not be wiped out. The patients will still recall their phobia, but by weakening the memory, it is hypothesized that the bodily fear response will be weakened as well. The next steps of the project will see clinical trials with Dutch war veterans and medical staff traumatized by experiences during the COVID-19 pandemic.
Training the brain to fight PTSD. Individuals with PTSD tend to have disrupted patterns of brain connectivity, but new research suggests that these patients may be able to “train their brain” using neurofeedback to restore healthy patterns of brain activity.
Neurofeedback, sometimes referred to as “brain training,” uses a system called a neurofeedback loop, in which a person’s brain activity is measured through sensors placed on the scalp and displayed back to them using a computer interface. Through these means, the patient can effectively learn to regulate their own brain activity—and ultimately their own states of consciousness, thought, mood, and emotion. Researchers studied 72 participants, including 36 with PTSD and 36 healthy controls. Following therapy, 61.1% of participants no longer exhibited symptoms that met the definition for PTSD. This suggests that neurofeedback could be an effective and accessible treatment option for the disorder.
Take a trip—it may help with that psychiatric disease. In a first, a new study has found a possible mechanism that explains how lysergic acid diethylamide (LSD) can increase social interaction. The findings of the study could lead to the development of therapeutic applications for the treatment of certain psychiatric diseases, like general anxiety or alcohol use disorders.
The study, published in the Proceedings of the National Academy of Sciences, involved administering low doses of LSD to mice over 7 days. Researchers found that the LSD activated the serotonin 5-HT2A receptors and the AMPA receptors in the prefrontal cortex and a cellular protein called mTORC1. As a result of these mechanisms, the social interactions of the mice increased. The researchers intend to continue their trials by testing the ability of LSD to treat mouse models displaying behavioral deficits similar to those seen in human pathologies, such as autism spectrum disorders, social anxiety disorders, and alcoholism.
Study sheds light on inflammation of gray matter in MS. Multiple sclerosis begins when nerve cells are attacked by the body’s immune system. It can then progress with a shift of pathology from the white matter to the gray matter—a phase of the disease that’s difficult to treat because its underlying causes remain poorly understood. New research, published in Nature Neuroscience, has shown in an MS mouse model that inflammation of the gray matter leads to a decrease in nerve-cell activity through the destruction of synapses. This research could lead to the development of therapeutic approaches that will effectively curb the progression of MS.
Loss of synapses is an early indicator of damage to the cerebral cortex in patients with progressive MS. As such, the researchers hypothesized that the synapses are the key to neuronal damage that occurs in this stage of the disease. Using various imaging techniques and mouse models, they found that synaptic spines are destroyed by a specific type of immune cells. Targeted inhibition of these specific immune cells could slow down synapse damage, the findings suggest.
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CD4+ T and natural killer cell ratios could suggest MS activity. While research is shedding more light on how multiple sclerosis progresses, many aspects of the pathogenesis and mechanisms of the disease remain unclear. A new study has found that ratios of natural killer cells to CD4+ T cells could serve as a prognostic biomarker for disease activity in MS patients.
The study, published in the European Journal of Neurology, looked at the NK and T cell subsets of 50 relapsing-remitting MS patients who were taking part in a vitamin D supplementation study. Using flow cytometry to analyze baseline peripheral blood mononuclear cells, researchers found a negative correlation of the proportion of NK cells with CD4+ T cells and interleukin 17A (IL‐17A+) CD4+ T cells. Lower NK/IL‐17A+ CD4+ T cell ratios were detected in participants with MRI activity or relapses. Researchers saw a negative correlation of NK/IL‐17A+ CD4+ T cell ratio with neurofilament light chain levels. The findings suggest that expanded NK cell compartment appears to serve a protective role in relapsing-remitting MS patients, compared to CD4+ T cell subset fractions.
Pulse down to electric avenue: That’s how you stop the tremors. Tremors are a common symptom of a number of neurological diseases. But, considering their underlying cause is largely unknown, tremors are notoriously difficult to treat. Enter the research team that developed a new way to manage tremors— using non-invasive electrical pulses to inhibit rogue brain waves.
The research, published in Nature Communications, saw researchers track and analyze the phase of the aberrant brain waves associated with tremors in real time in 11 patients. Then they identified synchronized peaks and troughs of this activity. Electrodes were placed on the patients’ scalps, and brain stimulation was targeted toward the cerebellum—the region of the brain that coordinates movement—when the tremor-related brain waves occurred. Researchers reduced symptoms of Essential Tremor Syndrome during stimulation and for a short period afterward. They hope that this will lead to the development of a treatment for tremors that works on a long-term basis.
Strike up the band to help dementia patients. A recent study suggests that playing familiar music to patients with Alzheimer’s-type dementia can elicit an extended emotional response, which could lead to more effective music-based therapies.
The research, recently published in the Journal of Alzheimer’s Disease, jumps off from the belief that music has emotional and behavioral benefits. Investigators sought to establish whether these emotions could be provoked without any “declarative memory,” which refers to the conscious recollection of the particular piece of music. The study looked at 20 patients with dementia and a control group of 19. All participants were asked to listen to a selection of music of their choice and report their feelings before and after each session. While the dementia patients exhibited “impaired memory for music selections,” both groups reported similar levels and duration of emotional response to the stimuli. The findings suggest that lasting emotion can be induced without memory being the cause of that emotion. That could mean big news for musical strategies as an effective therapeutic tool in caring for Alzheimer’s patients.
Can this common painkiller prevent spinal damage? Gabapentin is widely prescribed as a painkiller, but new research has found that the drug can prevent harmful structural changes in the injured spinal cords of mice. What’s more, the drug could block cardiovascular changes and immune suppression caused by spinal cord injury.
The research, published in Cell Reports, was led by The Ohio State University Wexner Medical Center and College of Medicine. After traumatic spinal cord injuries, structural changes tend to occur within spinal autonomic nerve centers, resulting in uncontrolled autonomic reflexes. Autonomic dysfunction can increase blood pressure and long-term immune suppression, which raises the risk of morbidities like heart attack and stroke, and infections such as pneumonia. By conducting experiments with mice, researchers found that gabapentin, if given after an injury but before symptoms develop, can limit structural changes to those nerve cells, which may prevent all these complications. Researchers don’t know whether gabapentin affects other cells or organs in the body or how long these effects might last. However, they say gabapentin could be repurposed as a prophylactic therapy for spinal cord injury patients.
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Upcoming Medical Meetings
The following meeting is entirely virtual:
43rd Annual Carrell Krusen Neuromuscular Virtual Symposium. February 18-19, 2021.
The following meeting is scheduled to have an in-person and virtual component:
American Academy of Neurology 73rd Annual Meeting (AAN 2021). San Francisco, CA. April 17-23, 2021.
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2021 Congress of Neurological Surgeons (CNS) Annual Meeting. Austin, TX. October 16-20, 2021.