Robot arms help stroke survivors, a stinky gas that could protect your brain, and biologists identify the first neurons hit by Alzheimer’s

We’ve got a major breakthrough for you in Alzheimer’s disease research: For the first time ever, a team of scientists has identified which neurons are the first to be affected by the disease, potentially paving the way for therapies to build up neuronal resilience. This week, we also have research suggesting that recent depression diagnoses could be a predictor of impending dementia—but only in women. Plus, details on a trial demonstrating that a mind-controlled robotic arm might provide rehab options for stroke patients, and much more.

Neuro Flashback

Rickman J. Godlee performed the first recognized reduction of a primary brain tumor on Nov. 25, 1884. The operation took place in London, England, at the Hospital for Epilepsy and Paralysis in Regents Park. While the world had already seen operations on intracranial tumors, those procedures focused on extracerebral meningeal or osseous tumors. Godlee’s patient died 28 days later of what appeared to be meningitis and secondary complications. However, postmortem examination revealed no remnant of the excised glioma. Highly detailed descriptions of Godlee’s operation dominated the press and, according to some, paved the way for further surgeries and possibly even the advent of modern neurosurgery.

In the News

Could this EEG helmet detect Alzheimer’s before it starts? There is still no simple, reliable way to diagnose Alzheimer’s disease, but a biotech startup might soon change that. Recently, iMediSync announced the launch of an EEG product that uses AI brain mapping to detect preclinical AD by monitoring brainwaves.

As the brain degenerates, brain waves begin to slow down, but this process is hard to spot. As such, iMediSync says it’s developed an AI cloud platform called iSyncBrain, which uses analytics and brain-mapping techniques to learn what this slowdown looks like. The company claims that its technology can discriminate between the likes of AD and mild cognitive impairment with more than 90% accuracy in trials. The company plans to showcase its tech at CES 2021, so stay tuned to see if reality lives up to the hype.

Study shows COVID-19 virus can directly affect the central nervous system. Scientists have long suspected that SARS-CoV-2 can affect brain cells and leave long-lasting neurological damage. But now, a study that used both mouse and human brain tissue has demonstrated that the virus can directly infect the central nervous system—and researchers are finally beginning to discover its effects on brain cells.

The study, conducted by researchers at Yale School of Medicine and published in the Journal of Experimental Medicine, looked at the ability of SARS-CoV-2 to invade human brain organoids, which are miniature 3-D organs grown in a lab using human stem cells. The researchers found that the virus can infect neurons and subsequently use the neuronal cell machinery to replicate. Researchers also looked at the brains of three patients who died from the virus, and they found SARS-CoV-2 in the cortical neurons of one of those patients. According to the study, the infected brain regions were associated with ischemic infarcts due to decreased blood supply causing tissue damage and cell death.

Biologists identify first affected neurons in Alzheimer’s. Up until now, a diagnosis of Alzheimer’s disease (AD) came after the disease had already taken hold—and where the disease started remained unknown. For the first time, however, a team of molecular biologists and neuropathologists from the University of California-San Francisco, Weill Institute for Neurosciences has identified which neurons are the first to be affected by AD.

The research, published in Nature, involved using single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus to identify vulnerable neuronal populations. These brain regions are where neuronal loss occurs early and late in AD, respectively. The team identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex. Their characterization of selectively vulnerable neurons could lead to more studies and, ultimately, therapeutic strategies for enhancing neuronal resilience.

Eli Lilly announces AD drug slows symptoms by 30%. While its claims have yet to be published or peer-reviewed, Eli Lilly has announced that donanemab, an investigational drug targeting beta-amyloid, appeared to slow onset of AD symptoms in patients by more than 30% in a Phase II study.

The drug targets a modified form of beta amyloid known as N3pG. Eli Lilly claims that the drug demonstrated significant slowing of declines in cognition and daily function vs placebo in the TRAILBLAZER-ALZ study. Over the years, various beta amyloid-targeting drugs have failed when they reached clinical trials, but Eli Lilly claims that this drug is different. By targeting N3pG beta amyloid, the company says, donanemab treatment can rapidly result in high levels of amyloid plaque clearance. In the phase II trial, the drug reportedly left patients with an 84 centiloid reduction of amyloid plaque on average at 72 weeks, compared with a baseline level of 108 centiloids. The company plans to discuss findings with regulators before it plans its next steps.

Neuro Trivia

Question: How many brains does a leech have?

Answer: A freshwater leech’s body is separated into 32 segments, each with its own brain. Therefore, a leech can be said to have 32 brains. Of note, these types of leeches also have 10 stomachs and nine pairs of testicles.

Novel Diagnostics

Time to start paying closer attention to occlusion site and thrombus length. Early neurological deterioration, also known as END or “stroke progression,” occurs in up to 40% of stroke survivors. But a new study suggests that END of ischemic origin (ENDi) can be reliably predicted in patients with IV thrombolysis (IVT)-treated minor strokes and large-vessel occlusion (LVO), using an easily applicable score based on occlusion site and thrombus length.

The study, published in JAMA Neurology, looked at 729 patients with minor stroke and LVO who were intended for IVT alone. Researchers found that a score based on occlusion site and thrombus length—two independent predictors of ENDi—showed good discriminative power for ENDi risk prediction. They confirmed the result in an independent cohort of 347 patients. Researchers concluded that this predictive system may help to select the best candidates for direct transfer for additional thrombectomy.

Junk DNA could be biomarkers for mild cognitive impairment. MiRNAs have been the subject of a variety of recent research, as scientists begin to uncover that they have far more significance than previously understood. Now, a new study indicates that circulating miRNAs are significantly linked to severe cognitive decline, cellular oxidative stress, and apoptosis in patients with mild cognitive impairment (MCI).

The study, published in Clinical Interventions in Aging, looked at 150 older adults (aged 65.4 ± 3.7 years), all of whom had MCI. Researchers aimed to analyze the role of circulated miRNAs in the development of MCI, as well as their relationships with things like cellular oxidative stress and apoptosis. They found that, in the serum of the 70 MCI patients, levels of miR-124a and miR-483-5p were increased significantly, and miR-142-3p and miR-125b were significantly decreased, compared to the 80 participants in the control group. Circulating miRNAs were significantly linked to severe cognitive decline, cellular oxidative stress, and apoptosis in MCI patients. As such, the findings suggest that these could be used as possible noninvasive biomarkers for MCI diagnosis.

Bad news for those with arthritis and CV risk factors. Patients with rheumatoid arthritis (RA) and cardiovascular (CV) disease, or even just CV risk factors, are more likely to have to contend with another ailment later in life: Dementia.

A new study, published in Seminars in Arthritis and Rheumatism, used Centers for Medicare & Medicaid Services claims data from 2006 through 2014 to analyze patients with RA who were 65 years of age and older. Researchers compared the incidence of dementia in patients who also had prevalent CVD, those who had CV risk factors but no prevalent CVD, and those who just had RA. Among a cohort of 56,567 patients with RA, 11,789 cases of incident dementia emerged. Those with either CVD or CV risk factors were at an increased risk of dementia, according to the findings.

Feeling down? That could be a sign of impending dementia. There are numerous risk factors for Alzheimer’s disease for both men and women. But, according to a recently published study, recent depression could be a predictor of AD development in women, but not men.

The study, published in The American Journal of Geriatric Psychiatry, used the National Alzheimer’s Coordinating Center database to analyze older adults (age 50+ years) with normal cognition who visited memory clinics across the country between 2005 and 2019. Of the 10,739 participants, 652 developed AD over a median follow-up of 55.3 months. Researchers found an independent association of recent (within 2 years) diagnoses of depression with increased risk of incident AD. This observation did not correlate with remote depression. On top of that, this association appeared only in women, leading researchers to conclude that recent depression may be predictive of AD development only in females.

Novel Treatments

Mind-controlled robotic arm could be rehab for stroke patients. Not all survivors of stroke respond to conventional rehabilitation. For those who don’t, a new trial and an unlikely device might offer some hope. The trial showed that certain stroke patients gained clinically significant arm movement and control by using an external robotic device powered by the patient’s own brain.

The clinical trial, whose results were described in the journal NeuroImage: Clinical, involved training stroke survivors with limited movement in one arm to use a brain-machine interface attached to an exoskeleton fixed to that arm. The interface used a computer program to capture brain activity and translate the patient’s intentions into the movement of the robotic arm device. In doing so, the device used brain plasticity to help participants relearn movements. The trial involved 10 patients between the ages of 41 and 71 years and took place over 4 weeks. While it remains unclear whether the benefits will persist in the long term, the trial shows promise for this novel treatment.

For basilar artery occlusion, two treatments may be better than one. Basilar artery occlusion (BAO) can be a potentially fatal diagnosis, and it’s notoriously difficult to manage. But new research suggests that patients who’ve suffered a minor stroke with BAO could find success in bridging therapy. Combining IV thrombolysis and mechanical thrombectomy is associated with an excellent outcome vs IVT alone.

The multicentric retrospective observational study, which was published in Stroke, was undertaken to determine whether bridging therapy is superior to IVT alone as a treatment following minor stroke with BAO. The study looked at 57 patients with minor stroke (National Institutes of Health Stroke Scale score ≤ 5) with BAO, roughly half of whom were subject to IVT alone, and the other half subject to bridging therapy. Researchers found that the latter tended to experience an excellent outcome, compared to those who underwent IVT alone. So, in this case, two treatments really are better than one.

For MS patients, a new precision drug inspires hope. Autoimmune diseases like multiple sclerosis (MS) occur because of a breach of immunological self-tolerance and tissue damage by autoreactive T lymphocytes. As such, the aim when treating an autoimmune disease is to control autoreactive T cells without inducing systemic immune suppression. Unfortunately, many current treatments can cause this kind of suppression, resulting in side effects like increased risk of infections. However, a new study has found that BioNTech’s experimental non-inflammatory vaccine—which is designed to dampen the abnormal immune responses seen in MS against myelin—can delay the onset and lessen the severity of MS symptoms in a mouse model.

The study, published in Science, examined the capabilities of a nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA vaccine. The vaccine lacks adjuvant activity and delivers MS autoantigens into lymphoid dendritic cells. In mouse models of MS, the vaccine slowed the progression of MS and reduced its symptoms without resulting in general immune suppression, according to the findings.

New metal alloy nanozyme could halt Parkinson’s. Nanozymes are essentially synthetic nanomaterials that mimic the functions of the enzymes. Sound a bit too futuristic? Maybe. But a new study suggests that a recently developed antioxidant metal-alloy nanozyme can reduce the build-up and transmission of the disease-causing alpha-synuclein protein in the nerve cells and brains of mice with Parkinson’s disease.

The study, conducted by scientists in China and published in the journal Nano Today, was helmed by an assistant professor of neurology at Johns Hopkins University School of Medicine. PD is characterized by the build-up of alpha-synuclein protein fibers (aggregates) called Lewy bodies in the nervous system. This is driven in part by oxidative stress, which can lead to cell and tissue damage. To block aggregate spread, the researchers developed an antioxidant metal-alloy nanozyme using platinum and copper called PtCu bimetallic nanoalloy. The nanozyme was then tested to see whether it would reduce oxidative stress and prevent the spread of alpha-synuclein aggregates in cells and in a number of Parkinson’s animal models. Researchers found that the nanozyme significantly inhibited the neurotoxicity induced by alpha-synuclein. They hope that the nanozyme can be considered for development as a therapeutic strategy.

New in Patient Management

This stinky gas may help protect cells from Alzheimer’s. There are a number of proven ways to help protect against dementia and cognitive decline, but this method may smell the worst. According to newly published research, hydrogen sulfide may help protect aging brain cells against Alzheimer’s disease.

The study, published in Proceedings of the National Academy of Sciences of the United States of America, was conducted on the basis that hydrogen sulfide is created by the body to help regulate functions across the body via cell signaling. Previous studies have found that sulfhydration levels in the brain decrease with age—a trend that is augmented in patients with AD. The new study looked at mice models of AD, which were injected with a hydrogen sulfide-carrying compound, which slowly released hydrogen sulfide molecules while traveling throughout the body. Over the 12-week study period, researchers found that cognitive and motor functions in the mice improved by 50%. In addition, the mice began remembering locations and becoming more physically active than the control group. Sure, hydrogen sulfide might smell like rotten eggs, but it could represent an AD breakthrough that certainly doesn’t stink.

How do you sleep at night? For stroke survivors, not that well. Patients who survive a stroke need all the rest they can get. But new research suggests that this isn’t easy. According to a recently published review in Stroke, sleep disorders after stroke or transient ischemic attack (TIA) are highly prevalent, which highlights the importance of early screening and treatment.

The systematic review and meta-analysis aimed to determine the prevalence of sleep-disordered breathing, insomnia, periodic leg movement during sleep, and restless leg syndrome following stroke or TIA in acute, subacute, and chronic phases. Researchers also examined the moderating influences of patient characteristics (like age) and methodological features (like study quality) on this prevalence. Using data on more than 64,000 adults from 169 studies, researchers found that the prevalence of periodic leg movement during sleep in the acute, subacute, and chronic phases was 32%, 27.3%, and 48.2%, respectively. They concluded that, over time, sleep disorders after stroke or TIA are very common. Early screening for post-stroke or TIA sleep disorders, it turns out, is key for helping patients recover.

New plasma-biomarker illuminates progression of AD. Monitoring the progression of AD can be a tricky business, but a recent study showed that plasma p-tau181, either alone or combined with plasma neurofilament light chain, can be used as an accessible and minimally invasive biomarker to track how far along Alzheimer’s disease has progressed.

The study, published in JAMA Neurology, used data from the Alzheimer’s Disease Neuroimaging Initiative, a multicentric observational study of 1,113 participants from 2007 to 2016. Follow-up blood sampling was performed for up to 8 years, and plasma p-tau181 measurements were performed in 2020. Researchers found that baseline and longitudinal increases of p-tau181 in blood plasma were associated with progressive, longitudinal neurodegeneration in brain regions that are typical for AD, as well as with cognitive decline, in participants who exhibited elevated brain amyloid-β. Neurofilament light chain in plasma, however, was associated with disease progression independent of amyloid-β and plasma p-tau181.

What imaging factors can tell us about first-line treatment for MS. Treatment options for patients with multiple sclerosis have shifted dramatically in recent years, with new, more potent medications becoming available for first-line treatment. However, for those with relapsing-remitting MS, first-line treatments can occasionally fail to be effective. A new study has spotlighted a path to correct this. The study’s findings show that several clinical and imaging factors, including age at treatment initiation, Expanded Disability Status Scale (EDSS) score, and annualized relapse rate, are good predictors of first-line treatment failure in patients with a recent diagnosis of relapsing-remitting MS.

The study, published in Multiple Sclerosis and Related Disorders, involved a retrospective analysis of 863 patients from three large tertiary French MS centers. Of these patients, 185 required a switch to second-line therapy, while the rest continued with first-line treatment. Over a follow-up period of just over 5 years, treatment failure was reported in roughly 23% of patients. Researchers found that young age at onset (< 26 years) and EDSS ≥ 2 were the two main predictors of treatment failure. Higher relapse rate and gadolinium-enhancing lesions also predicted treatment failure. Researchers concluded that some clinical and imaging factors are associated with treatment failure. As such, they should be considered when planning treatment strategy in patients with recently diagnosed RR-MS.

Latest in Journal Summaries

Estimating the causal effects of modifiable, non-genetic factors on Huntington disease progression.

Microbleeds and anticoagulation in patients with embolic stroke of undetermined source.

Patient-assisted intervention for neuropathy in real-life situations.

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Upcoming Medical Meetings

The following meetings are entirely virtual:

54th Annual Recent Advances in Neurology. February 10-12, 2021.

Mayo Clinic Multiple Sclerosis and Autoimmune Neurology Update 2021 – Livestream. February 5-6, 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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