A new controversial Alzheimer’s test, cannabis for migraine, and what overdue bills tell us about dementia

A whole host of new tools for the early detection of Alzheimer’s disease may be on the horizon. This week: A new blood test to help diagnose AD has gone on sale, but with a catch. Also, we bring you up to speed on a group of researchers who discovered a new blood-based biomarker for dementia, and dive into how exposure to power plants and car pollution could also be a significant risk factor for the disease. Plus, new studies on cannabis, the neurological benefits of having more babies, and much more.

Neuro Flashback

Nearly 350 years ago, Thomas Willis, a pioneering brain anatomist, wrote in his journals about a “prudent and honest woman” who was experiencing fluctuating muscle weakness “not only in the members but also in her tongue.” It may not sound like much—and Willis may not have realized it when he wrote the words in 1672—but by 1903 this brief passage was recognized as the first-ever recorded case of myasthenia gravis, which literally translates to “grave muscular weakness.”

In the News

Non-FDA-approved blood test for AD goes on sale. The first ever blood test to help diagnose Alzheimer’s has gone on sale. The only catch: It hasn’t been approved by the FDA yet. While independent health experts are wary of the new blood test—manufactured by C2N Diagnostics in St. Louis—due to the lack of published test results, others are hailing it as a cheap and effective way to diagnose AD.

One of the key ways to diagnose the disease is to measure the buildup of proteins like beta-amyloid in the brain. Currently, the best way to measure the protein is via PET brain scans, which are typically expensive and often not covered by insurance. The new blood test measures two types of amyloid particles, as well as other forms of protein, to establish whether someone has a certain gene that raises risk for Alzheimer’s. When combined with other factors like age, the test can determine the likelihood of having a potentially dangerous level of amyloid buildup in the brain. While the test is not yet covered by insurance or Medicare, it costs $1,250 a pop. It’s sold in all but a few states and must be ordered by a doctor. Results typically arrive within 10 days.

A quick workout for quick wit. It’s long been held that inactivity and obesity are risk factors for dementia and that physical exercise can help protect against the disease. But a new study has shown that even just 10 minutes of physical activity a few times a week can slow dementia progression in those with mild cognitive impairment. 

According to prior research, about 15% to 20% of those over the age of 65 years have mild cognitive impairment (MCI). There is currently no medication approved by the FDA to treat it, and drugs that have been approved to treat Alzheimer’s have not been shown to delay or prevent the progression to Alzheimer’s from MCI. This new study was based on data collected on almost a quarter of a million people diagnosed with MCI. Over 6 years, researchers monitored the participant’s lifestyles and found an 18% risk reduction of progression in those who exercised regularly both before and after diagnosis. The findings also indicated that even those who only started exercising after diagnosis still reduced their risk of disease progression by 11% vs those who did not exercise at all. So what’s behind the data? The study’s authors believe that exercise supports the production of brain cells and increases blood flow to the brain, countering the shrinking effect caused by dementia.

Migraine sufferers may need weed. Migraines and their symptoms can be severely debilitating and tricky to treat. Even approved medications don’t work for everyone who suffers, which often leaves people seeking alternative treatments. According to one new study of migraine-sufferers, the alternative treatment is often cannabis, which many patients report works better than prescription drugs.

The study, conducted at the University of Colorado, Boulder, aimed to explore how migraine sufferers use cannabis and whether it’s an effective treatment. The team looked at 589 cannabis users who completed an online survey about their cannabis use, their experiences with migraines, and a number of other factors. Of those participants who experienced migraines, roughly 70% reported having used both cannabis and prescription meds to help alleviate symptoms. Researchers found that roughly three-quarters of these individuals reported cannabis as an effective treatment for migraines, while roughly half reported relief from non-cannabis products. Of course, there is still very little known about the medicinal properties of cannabis and how it interacts with the brain, but the findings of this study certainly appear to warrant further research.

Fewer pregnancies may predict MS. One of the strongest risk factors for multiple sclerosis is being female. According to some estimates, women are 2-3 times more likely than men to develop MS after puberty. And if you’re a woman who’s never given birth, your chances may be even higher, according to a new study.

The new cross-sectional study looked at more than 500 women—137 of whom had MS. The researchers found that those who’d had fewer births or who had never given birth were more likely to develop early onset MS. Likewise, the study found an association between a higher number of pregnancies and a protective effect in delaying the disease. Beyond this, the findings also indicated that entering menopause earlier—that is, before the age of 46—is also linked with the progression of early onset MS. The findings suggest that both hormonal and environmental factors play a role in the development of MS, which could help pave the way for much-needed new treatments.

Neuro Trivia

How much does the average brain weigh, and what makes up the majority of that weight?

The average brain weighs about 3 pounds, and the majority of that weight (about 75%) is water.

Novel Diagnostics

Blood holds clues to future Alzheimer’s. Before the development of dementia, patients will often experience MCI, which can remain stable or progress to become a disease like Alzheimer’s. Accurate prognosis at this stage is huge, because it helps determine how to appropriately treat a person’s MCI. Recently, a team of scientists discovered a new method for predicting whether patients will develop Alzheimer’s disease by analyzing their blood for certain biomarkers.

The team followed 148 patients, monitoring plasma and CSF biomarkers such as levels of Aβ, tau, and neurodegeneration. The researchers were aiming to test which subset of plasma biomarkers best predicted individual risk for cognitive decline and progression to Alzheimer’s disease. The model they used resulted in the emergence of two proteins, which they could then use to predict the progression of the disease with an 88% success rate over 4 years. If disease-modifying treatments become available, these biomarkers could be vitally important in guiding patients who are likely to develop Alzheimer’s toward early treatment.

Another way to predict Alzheimer’s development. Among a flurry of new research regarding Alzheimer’s disease last week, one team of researchers in Europe has found new forms of tau protein that become abnormal in the early stages of Alzheimer’s disease—prior to the emergence of noticeable symptoms. The team developed new tools to detect these small changes, which could be used in the future for early detection of the disease.

As Alzheimer’s disease progresses, amyloid beta and phosphorylated tau are released from the brain into CSF, which is used as a reliable marker for clinical diagnosis of Alzheimer’s disease. Currently, tests for p-tau are only effective once the patient’s memory begins to fail, which in many cases is too late for meaningful intervention. Recently, researchers at the University of Gothenburg in Sweden, together with their colleagues at the Barcelona Beta Research Centre in Spain, the University Medical Centre in Ljubljana, Slovenia, and the University of Paris, discovered that there are specific forms of p-tau that undergo very small increases in CSF and blood in people who are in the early stages of developing Alzheimer’s disease. The team found that progressive increases in p-tau could provide insights into the biological and clinical development of Alzheimer’s disease. The newly discovered tau protein is now the earliest detectable Alzheimer disease change in the brain. More studies are needed to determine this method’s validity, but there’s no doubt that more biomarkers are better biomarkers.

New markers can discern palsy from Parkinson’s. Quantitative MR planimetric measurements have been reported to show clear differences between progressive supranuclear palsy (PSP) and non-PSP parkinsonism. Now, a new study has provided evidence that this technique offers a high degree of diagnostic accuracy in separating out the conditions, which are often mistaken for one another.

The study looked at 84 patients with clinically unclassifiable neurodegenerative parkinsonism at the time of initial imaging. Researchers analyzed a number of indices, like the pons-midbrain ratio and the Magnetic Resonance Parkinsonism Index, among others. The findings revealed that brainstem-derived MR planimetric measures yield high diagnostic accuracy for separating PSP from non-PSP parkinsonism in early disease stages when clinical criteria are not yet fully met. The key takeaway? The research could lead to advances in early and accurate diagnosis for PSP patients.

Dementia and finances. Early onset dementia has several tell-tale signs, but one study has found a rather unusual one. According to a new study led by researchers at the Johns Hopkins Bloomberg School of Public Health and the Federal Reserve Board of Governors, older adults with dementia are more likely to miss payments on bills as early as 6 years before a clinical dementia diagnosis.

The study looked at information on 81,364 Medicare beneficiaries living in single-person households between 1999 and 2014. During this time, 27,302 received a dementia diagnosis, while 54,062 did not. The researchers then compared financial outcomes for participants between 1999-2018, focusing specifically on things like missed credit card payments and subprime credit scores. Researchers found that Medicare beneficiaries with dementia were more likely to have missed payments on bills up to 6 years prior to diagnosis. Additionally, they found that beneficiaries diagnosed with dementia who had lower levels of education tended to miss payments on bills as early as 7 years before a clinical diagnosis, compared to 2.5 years prior to a diagnosis for beneficiaries with higher educational status. The findings suggest that missing payments on routine bills could be used as an early indicator of possible dementia development. They also support the idea that dementia can lead to costly financial errors, irregular bill payments, and increased susceptibility to financial fraud.

Novel Treatments

Dexamethasone’s downside. Patients with cancer undergoing chemotherapy are often given dexamethasone to counter the side effects of the treatments they receive, and it is also used to treat patients with brain cancer to fight edema. The corticosteroid has antiinflammatory and immunosuppressive effects, but a new study suggests that the drug decreases the efficacy of immune checkpoint inhibitors in patients with glioblastoma.

The study, which was presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs, found that dexamethasone use was associated with shorter survival both in a glioblastoma animal model and among a group of 181 patients with glioblastoma who were treated with programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors. Researchers noted that samples of mouse tissue showed that dexamethasone decreased systemic lymphocytes, intratumoral CD4-positive lymphocytes, and reduced T-cell production of interferon-γ. The drug also induced apoptosis of multiple types of immune cells. While there is growing evidence that corticosteroids can exert detrimental effects on immunotherapy for cancer patients, the study’s findings indicate that the drug could pose some seriously negative effects on the immune system too.

Cannabis trial begins for Alzheimer’s patients. To date, no effective cure has been found for Alzheimer’s disease. A new trial, though, conducted by India Globalization Capital, Inc., may help us find an effective therapy that reduces its burden. Last month, the company announced it is enrolling participants for a Phase 1 clinical trial to test the effects of a new investigational low-dose, cannabis-based treatment for Alzheimer’s disease.

The Phase 1 study will be placebo-controlled and will involve three 14-day periods, during which dosage will be increased. Participants will be monitored daily, and researchers will measure how fast the drug is absorbed through the body, how long it lasts in the body, and whether different people process it differently based on polymorphisms of the liver enzyme CYP450 2C9. The company has already conducted pre-clinical trials that involved testing the drug on in vitro cells and in animals. Now the company is looking for people suffering from mild-to-severe dementia due to Alzheimer’s disease for a study that researchers anticipate completing during the first half of 2021.

Gene-editing may prevent Alzheimer’s. Around one in four people over the age of 90 years have Alzheimer’s disease, but new evidence suggests that it may not have to be that way in the future. A team of scientists at Laval University in Quebec, Canada, recently discovered that it may be possible to decrease a person’s chances of developing Alzheimer’s disease by editing a key gene in their nerve cells.

We know that Alzheimer’s disease is caused in part by the buildup of the protein beta-amyloid on brain cells, and that studies have shown that people who express a gene variant called A673T are four times less likely than the general public to develop Alzheimer’s. The team at Laval looked into whether it’s possible to use CRISPR gene-editing technology to give people this variant to reduce their chances of developing the debilitating disease. Using a new technique known as “prime editing,” the team found they were able to edit roughly 40% of brain cells in an in vitro experiment. While the researchers note that this would not be enough to prevent the build-up of beta-amyloid, it’s promising enough to warrant further research.

Rozanolixizumab may help myasthenia gravis. While there are various treatment options for myasthenia gravis, a lot of them have pretty bad side effects. A new study has found that the fun-to-say drug rozanolixizumab may be a good solution to this problem. The Phase 2 randomized controlled trial of the drug provided evidence that rozanolixizumab is well-tolerated in patients with generalized myasthenia gravis, though it may not significantly improve the severity of the condition.

The trial sought to explore the clinical efficacy and safety of subcutaneous rozanolixizumab, which is an anti-neonatal Fc receptor humanized monoclonal antibody. The randomized, double-blind, placebo-controlled, two-period, multicenter trial involved monitoring patients who received once-weekly infusions of rozanolixizumab or a placebo. Researchers found that the most common adverse effect experienced by patients was headache, with 57% of those on rozanolixizumab reporting that effect. While the overall data suggested the drug may have a clinical benefit, the change from baseline in Quantitative Myasthenia Gravis scores was not statistically significant. Phase 3 of the evaluation is ongoing—let’s hope for even better results.

New in Patient Management

Power plants, pollution, and Alzheimer’s. Several risk factors for Alzheimer’s disease are well-established, such as smoking and diabetes. New data, however, has revealed a host of additional risk factors, some of which may surprise you. These include exposure to forest fires, cars, power plants, and neighborhood air pollution.

The new study, led by researchers at UC San Francisco, looked at PET scans of more than 18,000 seniors throughout the nation, all of whom were suffering with dementia or mild cognitive impairment. Researchers found that those in the most polluted areas had a 10% increase in production of amyloid plaques—a hallmark of the disease—showing up on their PET scans. According to the study, if this figure is applied to the US population of Alzheimer’s patients (some 5.8 million), it indicates that exposure to microscopic airborne particles may have contributed to tens of thousands of cases. Researchers concluded that their findings added to a body of evidence that suggests pollution from the likes of cars, factories, power plants, and forest fires can join established Alzheimer’s risk factors.

Anxiety may speed up Alzheimer’s progression. While memory loss and confusion are the symptoms most often associated with Alzheimer’s, it’s common for those living with the disease to experience mood symptoms too, such as depression and anxiety. But those symptoms may be useful indicators for physicians. A new study suggests that feelings of anxiety are associated with a faster progression of the disease.

The study looked at 339 patients diagnosed with MCI. These symptoms don’t necessarily mean a quick slide into dementia, and declines in mental function can vary from person to person. That said, researchers are always looking for factors that may be linked to the fast progression of the disease. The study found that patients with more anxiety symptoms were more likely to develop Alzheimer’s over the next several years. So what does this mean? The researchers concluded that this suggests that heightened anxiety is a symptom of the disease’s fast progression, rather than a cause of it. Still, physicians should be aware so they can help manage the symptoms of anxiety and its effects on mental well-being.

Dismal outcomes for stroke survivors with COVID-19. Researchers are continuing to work around the clock to learn more about the different neurological complications that COVID-19 causes. One recently published study has found that patients infected with the disease have no increased risk of stroke. That’s the good news. But the bad news? Well, it’s pretty bad. The researchers concluded that if you’ve already had a stroke, your chances of surviving COVID-19 are significantly lower—in fact, you’d have a nine-fold increase in mortality risk.

The cross-sectional study looked at almost 25,000 patients discharged from a healthcare system in New York State between January-April 2020. Of those patients, 2,513 were diagnosed with COVID-19, and 566 had suffered an acute ischemic stroke. Researchers found that patients diagnosed with COVID-19 had one-quarter the odds of having a stroke compared with other patients. This association was found across all age groups. Of the patients who’d had a stroke, however, those who were also diagnosed with COVID-19 were found to have a nine-fold higher chance of dying. While more research is needed to reach a firm conclusion, the study suggests that concerns over a possible epidemic of young stroke victims as a result of the pandemic may not be necessary.

Z Drugs linked with increased risk of stroke. Issues with sleep are common among those with dementia. Some say as many as 90% of dementia patients experience sleep disturbances, and the impact of this on their physical and mental health—as well as on their families—can be significant. As there are no proven effective treatments available for this, patients are often prescribed drugs like zopiclone, zaleplon, and zolpidem to help them sleep. A new study, however, has shown that these so-called Z-drugs are linked to adverse neurological effects.

A team of researchers from UEA’s Norwich Medical School analyzed data from more than 27,000 elderly patients in England diagnosed with dementia between 2000-2016. The study looked at patients who were experiencing sleep disturbances and compared those who were prescribed Z-drugs, those who were prescribed benzodiazepines, and those who were not on sedatives. Researchers found that those on stronger doses of Z-drugs had an increased risk of falls, fractures, and stroke. These effects were found to be similar or even more severe than the adverse effects from a high dose of benzodiazepines. The team noted that patients already taking high doses of Z-drugs should not stop taking their medication suddenly, but should rather seek a review with their doctor.

Latest in Journal Summaries

Bumetanide for treatment of neonatal seizures.

The changing pattern of statin use in patients with dementia.

Impact of COVID-19 on acute ischemic stroke treatment times.

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Upcoming Medical Meetings

The following meetings are entirely virtual:

9th Annual Brain Tumor Symposium: Maintaining Excellence in the COVID-19 Pandemic Era. January 15, 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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