How your diet and exercise could be damaging your brain, a new hope for stroke patients, and the return of the opioids
There’s a lot going on this week, with researchers proving just how bad a popular but unhealthy diet can be for your brain, particularly for the hippocampus. They’ve also shared results from a phase 2 study showing that an experimental drug can actually preserve brain cells after stroke and improve outcomes. And, another experimental drug seems to have great effects in patients with myasthenia gravis, improving not only disease control but quality of life as well.
How memories are made. It was only 3 years ago that researchers from the Massachusetts Institute of Technology discovered how memories are formed initially and simultaneously in the hippocampus and the prefrontal cortex by specialized neurons (engram cells) that consolidate long-term memories over time.
In their seminal study, these researchers also found that long-term memories remain silent in the prefrontal cortex for about 2 weeks before they mature and are consolidated into permanent long-term memories. Also significant was their discovery of a labeling technology that allowed them to label specific engram cells, which enabled them to trace the brain circuity involved in the formation, storage, and retrieval of memories. With state-of-the-art optogenetics, they were able to switch on these cells in mice using bursts of light, which artificially reactivated memories held in specific engram cells. Now, if we could only figure out a way to remember where we left our keys!
In the News
Bad diet, bad brain. As the saying goes, you are what you eat. And, it’s no secret that the typical Western diet—which is high in fat, sugar, and junk food—isn’t good for you. (No surprises here.) The diet has been linked to increased risks of developing diabetes, obesity, and other health conditions like heart disease. Now, researchers have found that this dangerous diet may actually also affect your brain by disrupting the hippocampus, which affects both memory and appetite control. (You might want to read that sentence twice so you don’t forget it.) Specifically, in a recent study, people who followed a Western diet performed worse on memory tests and seemed to want to eat junk food, even when they were full.
Researchers studied the effects of a week-long fast food diet vs usual diets in 102 young, lean, healthy participants. Those in the junk food group had to eat two Belgian waffles at least four times a week and two fast food meals at least twice per week. Their food preferences and desire for more food were also rated and recorded. While their taste buds may have enjoyed it, it took a toll on their bodies. The Western diet was associated with a clear weakening of appetite control, as well as a decrease in learning and memory scores on hippocampal function testing. But, these negative effects disappeared 3 weeks after the diet was discontinued. Something to think about before you give in and eat those fries!
A blow to the wallet. As out-of-pocket costs rise for drugs that treat neurological disorders—such as Alzheimer disease (AD), peripheral neuropathy, and Parkinson disease (PD)—people are less likely to take the drugs as often as prescribed, according to a recent study funded by the American Academy of Neurology. Using a private insurance claims database for new cases of AD or other dementias, PD, and peripheral neuropathy over 15 years, researchers compared available drugs with different out-of-pocket costs. They found that $50 increases in out-of-pocket costs were associated with a lower adherence to prescriptions—with a 12% decrease in the medication possession ratio for drugs prescribed for AD and a 9% decrease for gabapentinoid drugs prescribed for peripheral neuropathy. Plus, patients who were Asian, African American, or Latino had larger drops in medication adherence rates compared with Caucasian patients for equivalent increases in out-of-pocket costs. It might be worth discussing adherence and out-of-pocket costs with your patients when prescribing.
Mix it up when working out. It turns out that certain kinds of exercise are great not just for your heart but your brain as well, while others may be harming it. Researchers have found that both high-intensity interval training (HIIT) and longer sessions of moderate exercise are the best when it comes to brain health. In their systematic review, the researchers assessed 128 participants after a single round of aerobic exercise (stationary bikes and treadmill) that ranged from low-intensity continuous exercise to HIIT, with heart rates between 5% and 90% intensity. The largest changes in neuroplasticity happened after 20 minutes of HIIT or 25 minutes of continuous moderate aerobic exercise. On the flip side, researchers noted that continuous cycling or running at full speed could actually work against you, as it may elevate your cortisol levels. And high levels of cortisol block neuroplastic responses. The take-home message: Mix up your exercise tempo—vary the aerobic intensity. This gives you a chance to cool down and then speed up again. So, the next time you’re lacing up your sneakers, remember to vary your pace to help improve your brain!
Guilty of neglect. Severe neglect during childhood may physically change the brain, according to a new study. Researchers found abnormal connections in the brains of rats that were neglected, especially in females. Specifically, the connections between the basolateral amygdala and the prefrontal cortex were disrupted. These were the same areas found to be affected in brain scans of children raised in orphanages and those who had experienced child abuse and other forms of severe mistreatment or neglect. Children with this abnormal activity are more likely to develop anxiety. When these connections are disrupted, maladaptive behaviors can result. In the study, female rats that were separated from their mothers demonstrated an excess of new, rapidly growing connections between the amygdala and the prefrontal cortex early in development. These connections disrupted the efficiency of the circuit, which resulted in suboptimal maturation and performance. When the rats were tested for anxiety-like behaviors, those with excess connections spent more time huddling in protective environments. In other words, these brain changes seemed to create a sense of hypervigilance. A good example of the importance of nurturing in nature, no?
What is sphenopalatine ganglioneuralgia?
Quite simply, it’s a brain freeze. During sphenopalatine ganglioneuralgia, the consumed cold substance (usually ice cream) constricts the vasculature at the very back of your throat, impeding the blood that’s in transit to and from your brain. This causes that excruciating pain in your forehead known as a brain freeze, which subsides as the blood vessels warm up, allowing normal blood flow to the brain to resume. One cure? Press your tongue to the back roof of your mouth. Voila! Instant relief.
Early clues found. Researchers have discovered that the Abl1 gene may play a key role in the hypersensitivity that is seen in neurodevelopmental disorders such as autism-spectrum disorder (ASD). They found, for the first time, that Abl1 is expressed and explosively activated during early development of inhibitory neurons in the mouse olfactory bulb. If expression or activation of Abl1 is inhibited (which the researchers did using a lenti-virus), it keeps inhibitory neurons from reaching the cell layers accurately. Then, using proteomics, they also found that Abl1 temporarily phosphorylated doublecortin, a cytoskeletal protein with a critical role in the brain’s structural development. What does all this mean? In patients with ASD, cognitive and sensory defects occur when the inhibitory neural circuit is not properly formed—due to either environmental or genetic factors during brain development. Understanding Abl1 may help to understand the hypersensitivity that appears in neurodevelopmental disorders like ASD, which could lead to earlier diagnosis of the sensory-defective symptoms that occur with these disorders. Thus, properly—or improperly—functioning Abl1 may offer clues for the early diagnosis of neurodevelopmental disorders.
Tracking iron deposits? The ability to find iron in the brain may lead to better and earlier diagnosis of neurodegenerative conditions like Parkinson disease (PD). Quantitative susceptibility mapping is a new cutting-edge MRI technique that may help map iron levels in the brain and track the progression of cognitive decline in patients with PD. Currently, clinicians rely on monitoring symptoms to do this because conventional brain imaging cannot track the progression of PD until the very late stages when large-scale loss of brain volume can be detected. When amyloid and tau proteins—linked to Alzheimer disease and PD dementia—build up, iron also accumulates in the affected areas. In 97 participants with PD, who received their diagnoses within the past 10 years, and 37 controls, researchers found that iron accumulations in the hippocampus and thalamus were associated with poor memory and cognition. Further, they found that iron buildup in the putamen was associated with poor movement. All of these areas are known to be affected by PD. This MRI mapping technique may be a great way to keep track of iron and cognitive decline in patients with PD!
New hope for stroke. Nerinetide (NoNO Inc.), an experimental neuroprotective drug, may effectively preserve brain cells for some time after stroke. Researchers found that giving nerinetide to patients who had suffered acute ischemic stroke, combined with endovascular treatment to remove the clot, improved outcomes. In the multicenter, double-blind, randomized ESCAPE-NA1 trial, they compared outcomes among 1,105 acute ischemic stroke survivors who were treated with nerinetide plus alteplase with those of survivors treated with only nerinetide. Both groups also underwent concurrent endovascular treatment to remove the instigating clots. About 20% more patients treated with nerinetide and endovascular treatment—but not alteplase—recovered from stroke. The benefits of nerinetide, however, were negated in those who also received alteplase. Researchers said there is evidence that nerinetide promotes brain cell survival until the clot is extracted. Their findings may lead to a new way to treat stroke!
A little stim-stim. Stimulation of the sphenopalatine ganglion (SPG) at the back of the nose could have beneficial effects in patients with stroke, according to two preliminary studies presented at the recent American Stroke Association’s International Stroke Conference 2020. Researchers demonstrated that SPG increased blood flow to the brain, improved hand strength in those with minor stroke, and decreased disability in those with severe stroke. All this from a treatment that consists of inserting a toothpick-sized electrode into the upper palate of the mouth that stimulates the cluster of nerve cells in the SPG. This action causes dilation of the blood vessels and enhances collateral blood flow to the brain, even without clot removal.
In the first study, researchers assessed 520 patients with cortical infarction who were unable to have stroke-causing clots dissolved or removed. In all, they estimated that for every 1,000 patients treated with SPG stimulation, 146 would be less disabled and 76 more functionally independent.
In the second study, a second group of researchers used electrodes and CT scans to place stimulation electrodes in 50 patients with anterior circulation ischemic strokes. SPG stimulation increased blood flow to the brain and head by an average of 44%. Furthermore, grips strength in the weaker arm increased by 26%, and pinch strength increased by 42% in the weaker arm. Seven days after treatment, those who received SPG stimulation had better improvements in total neurologic deficit scores compared with controls. Benefits occurred irrespective of the patients’ age, sex, severity of stroke, time before treatment, or side of body affected by weakness.
New Tx option for myasthenia gravis? Zilucoplan, a subcutaneously administered macrocyclic peptide inhibitor of complement component 5, has great potential for the treatment of patients with generalized myasthenia gravis, according to results from a phase 2 study. Because patients with generalized myasthenia gravis have significant clinical disability, persistent disease burden, and adverse effects due to chronic immunosuppression, new treatments are needed to not only improve disease control, but also enhance quality of life.
In their randomized, double-blind, placebo-controlled phase 2 trial, researchers enrolled 44 patients with moderate-to severe generalized myasthenia gravis who were acetylcholine receptor autoantibody-positive and had baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12. These patients were randomized 1:1:1 to daily subcutaneous self-injection of zilucoplan (either 0.1 or 0.3 mg/kg) or placebo for 12 weeks. The 3-mg/kg doses of zilucoplan significantly reduced QMG scores and MG Activities of Daily Living scores, and brought about significant improvements in MG Composite scores, and MG Quality of Life scores. Results with the 0.1-mg/kg dose were statistically significant as well in these areas, but results were slower and less pronounced compared with the 0.3-mg/kg dose. Zilucoplan’s safety and tolerability profiles were also favorable. Stay tuned: A phase 3 study is planned.
Comfortably numb? Certain opioid compounds, known as delta opioid receptor agonists, may one day help patients who suffer from PTSD. Researchers from the Tokyo University of Science and the University of Tsukuba, Japan, previously discovered the ability of these drugs to relieve symptoms of depression and anxiety in those with PTSD. In their recent study, the researchers found that two such agonists—KNT-127 and SNC80—can help in masking fear memories. Using a fear conditioning model of PTSD in mice, they found that both agonists reduced conditioned fear, but only KNT-127 suppressed contextual fear memory. And, it did this by increasing the levels of activated ERK, an enzyme involved in the ability to overcome fear condition. This may become an important new therapeutic option for patients with PTSD, for whom the most widely prescribed medication takes weeks to have an effect and may not be enough. These results bring hope for those suffering from PTSD and other anxiety disorders, and are being hailed as a breakthrough!
New in Patient Management
Racial disparities in risk of recurrent stroke. Compared with US white adults, US black adults face a higher risk of early stroke recurrence after a minor ischemic stroke or a transient ischemic attack (TIA), according to a recent study. It’s well known that black individuals have a substantially higher risk of incident ischemic stroke than white individuals, but no one has been able to pin down whether black individuals also have a higher risk of recurrent stroke. So, for this investigation—the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial—researchers enrolled 4,044 adults (22.7% black) who had a minor ischemic stroke or a high-risk TIA within the prior 12 hours. After 90 days of follow-up, the researchers found that black race was associated with a higher risk of stroke recurrence compared with white race (HR: 1.6), even after adjusting for demographics, comorbidities, and medication adherence.
“Our findings support research into black-white racial differences in the underlying mechanisms of recurrent stroke,” the authors wrote. “In the meantime, extra effort should be made to ensure that black patients have access to proven secondary prevention measures.”
Treatment of patients with OSA consists of positive airway pressure. Oxygen therapy alone in patients with OSA who cannot tolerate other therapies is not recommended. Furthermore, topical nasal steroids should not be used for the sole purpose of improving patient adherence to positive airway pressure treatment. For those with chronic insomnia disorder, cognitive behavioral therapy is recommended and is slightly favored over pharmacotherapy as first-line treatment. The use of antipsychotic drugs, benzodiazepines, and trazodone are not recommended, but a short-course of doxepin or a non-benzodiazepine benzodiazepine receptive agonist for chronic insomnia disorder is an option for patients with chronic insomnia disorder.
Happy wife, happy life? Yes, the saying is true: Having a happy, optimistic life partner can be really good for you. In fact, it can contribute to your good health by preventing neurodegenerative conditions like Alzheimer disease (AD), dementia, and cognitive decline as you grow older. Researchers followed almost 4,500 heterosexual couples from the Health and Retirement Study for 8 years to determine the relationship between spousal optimism and cognitive function. Intriguingly, they found a potential link between being married to an optimist and preventing the onset of cognitive decline—which is likely attributed to a healthier home environment, the researchers noted. People who were married to optimists tended to score better on metrics such as maintaining a healthy weight and getting enough physical activity. This finding is important, given that healthy lifestyle choices play a huge role in the development of cognitive conditions like AD and dementia. Plus, the researchers found that couples who recalled shared experiences together recollected richer memory details and more positive aspects of their relationship and partner personalities. But, can optimism be prescribed? Not really, however, researchers say it may be trainable. So, if you’re not already doing so, try to see the glass as half full whenever you can. And, if you can’t, hopefully you have a spouse who can!
Getting some ZZZZs. The US Department of Veterans Affairs and Department of Defense has released a new guideline on the management of chronic insomnia disorder and obstructive sleep apnea (OSA). Although sleep disorders are more prevalent in military personnel and veterans, chronic insomnia disorder may affect as many as 10% of US adults, and OSA may affect up to 38% of the general population. The guidelines recommend using the Insomnia Severity Index or the Athens Insomnia Scale as part of a comprehensive assessment of patients with suspected insomnia disorder, along with a careful history. They also recommend the use of the STOP questionnaire to assess risk for OSA.
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Upcoming Medical Meetings
American Society for Experimental Neurotherapeutics (ASENT) 2020 Annual Meeting , in Bethesda, MD, March 2-5, 2020
Multidisciplinary Neuro-Oncology Symposium: Updates in Medical and Surgical Management of Brain Tumors 2020, in Orlando, FL, March 6-7, 2020
North American Neuro-Ophthalmology Society (NANOS) 2020 Annual Meeting, in Amelia Island, FL, March 7-12
American Neuropsychiatric Association (ANPA) 31st Annual Meeting, in Philadelphia, PA, March 18-21, 2020.