Day: 02/19/2024

Test screening for 11 blood biomarkers could predict dementia 15 years sooner.

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An experimental blood test may be able to predict dementia 15 years before symptom onset.

  • Every 3 seconds, someone in the world develops dementia.
  • Because dementia disease progression may be slowed in its earliest stages, researchers are constantly working on better dementia prediction tools.
  • Scientists from The University of Warwick in the United Kingdom and Fudan University in China have identified 11 proteins that can be used as biomarkers to predict dementia 15 years before diagnosis.

Researchers estimate that every 3 seconds, someone in the world develops dementia — a condition affecting the brain that causes cognitive issues.

There is currently no cure for dementia. However, there are ways doctors can help slow the disease’s progression when caught in its earliest stages.

For this reason, scientists have been working on new ways to predict whether a person will develop dementia or not.

For example, a study published in August 2023 presented an 11-point risk score to predict dementia 14 years before diagnosis. And research published in October 2022 reported it is possible to see signs of dementia as early as 9 yearsTrusted Source before diagnosis.

Adding to this previous research is a new study from scientists at The University of Warwick in the United Kingdom and Fudan University in China that has identified 11 proteins that can be used as biomarkersTrusted Source to predict dementia 15 years before diagnosis.

The study paper appears in the journal Nature AgingTrusted Source.

Using blood proteins as biomarkers

For this study, scientists focused on proteins as biomarkers to help forecast if a person might develop dementia.

According to Prof. Jianfeng Feng, a professor at The University of Warwick in the U.K. and Fudan University in China, and the lead author of this study, the focus on proteins stemmed from their previous research.

“Last year we worked out a prediction methodTrusted Source using other types of data 10 years ago with an AUC (area under the curveTrusted Source) of 85%,” Prof. Feng told Medical News Today. “Proteins are much more reliable than a purely genetic approach using genes or SNPsTrusted Source [single nucleotide polymorphisms] only.”

This is not the first study to look at using proteins as biomarkers for early dementia diagnosis.

A study published in June 2023 identified the protein NPTX2Trusted Source as a potential biomarker for Alzheimer’s disease, which is the most common type of dementia.

And research published in October 2021 reported that blood proteins called microRNAs may be used to identify early Alzheimer’s disease risk.

Predicting dementia 15 years before diagnosis

Prof. Feng and his team analyzed blood samples of over 52,000 adults without dementia from the UK Biobank. These blood samples were collected between 2006 to 2010 and frozen.

As of March 2023, 1,417 people who provided blood samples had developed dementia. Using AI machine learning, the researchers identified 11 specific proteins found in the blood samples of the people who had developed dementia.

These 11 proteins were then combined into a protein panel. According to researchers, when also incorporating traditional dementia risk factors such as ageTrusted Source, genderTrusted Source, education levelTrusted Source, and genetics, they were able to predict a person’s likelihood of developing dementia up to 15 years before diagnosis with more than 90% accuracy.

The researchers stated these 11 proteins may offer new therapeutic targets for dementia medications. Additionally, they believe this prediction panel could be an important tool for screening middle to older adults who are at a high risk of dementia.

“This model could be seamlessly integrated into the NHS [National Health Service in the U.K.], and used as a screening tool by general practitioners,” Prof. Feng says.

When asked how quickly we may see an early diagnosis test for dementia based on these protein biomarkers, his answer was that, optimistically, it could be available in half a year.

“[Our next step for this research is] to test the currently available drugs on these subjects who are early diagnosed as risk subjects,” Prof. Feng added.

Importance of early dementia diagnosis

After reviewing this study, Dr. Jennifer Bramen, a senior research scientist at the Pacific Neuroscience Institute in Santa Monica, CA, told MNT that this study advances risk prediction using proteomicsTrusted Source.

“The ability to assess the risk of multiple diseases from a single blood test could be valuable for early detection and prevention,” Dr. Bramen explained.

“Early access to novel interventions for dementia, years before diagnosis, holds the key to potentially slowing disease progression. Treating individuals at this early stage, when they are likely to be more responsive to therapy, may significantly improve their long-term quality of life and cognitive outcomes.”

– Dr. Jennifer Bramen

MNT also spoke with Dr. Karen D. Sullivan, a board-certified neuropsychologist, owner of I CARE FOR YOUR BRAIN, and Reid Healthcare Transformation Fellow at FirstHealth of the Carolinas in Pinehurst, NC, not involved in the research, about this study.

Dr. Sullivan said it was a well-designed study and she liked the practical clinical utility of having one omnibus stratified risk score (ProRS) in place of multiple, cumbersome, and expensive lab tests that measure risk separately.

“Many dementias start on a neurophysiological level many years, if not decades, before their clinical manifestations of symptoms like cognitive decline or behavior change,” she continued.

That means that, “[b]y the time we see clinical symptoms in dementia, networks of brain cells have been ravaged by a disease process, and meaningfully changing the course is extremely challenging.”

“The earlier we know who is going to develop the subtypes of dementia, the earlier intervention we can offer and the better the long-term outcomes,” Dr. Sullivan added.

“That’s when we will have the power to find a cure or nip neurodegeneration in the bud. It has to be before it starts or at the very earliest changes. Waiting until we can measure symptoms in clinical assessments puts us way behind the eight-ball of meaningful medical treatment,” she told us.

More research needed

For the next steps in this research, Dr. Sullivan said, “[w]e need to see their models externally validated by other groups before we can consider bringing it to real-world patient populations.”

And Dr. Bramen commented that the current study primarily focused on a white European population, so further research should aim to work with cohorts of different ethnicities.

“To ensure generalizability, validating the findings in diverse populations would be an important next step,” she said. “Translating these findings into a practical clinical tool suitable for routine care will also require significant development.”

Acupuncture may help reduce stroke risk in people with rheumatoid arthritis.

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Research indicates that acupuncture may provide cardiovascular health benefits for people with rheumatoid arthritis. Kilito Chan/Getty Images

  • Rheumatoid arthritis is a debilitating disease and can affect the body in many ways, including negatively impacting the cardiovascular system.
  • Researchers based in Taiwan and China conducted a comparative study using data available on people with rheumatoid arthritis to see what sort of cardiovascular benefits acupuncture provided.
  • Acupuncture involves treating pain by inserting needles strategically in the body.
  • Their findings showed that people with rheumatoid arthritis who underwent acupuncture had a 43% reduced risk of having a stroke.

Rheumatoid arthritisTrusted Source (RA) is an autoimmune disease that can cause chronic joint pain, joint deformities, and inflammation.

According to the National Institutes of HealthTrusted Source (NIH), rheumatoid arthritis affects millions of people worldwide, with up to 1% of some countries’ population having rheumatoid arthritis. The NIH notes that between 25 to 27.5 people per 100,000 in the U.S. have rheumatoid arthritis.

With rheumatoid arthritis being so prevalent, researchers are looking for ways to treat the disease as well as some of the problems associated with the disease, such as cardiovascular disease.

Researchers in China and Taiwan recently accessed medical records to see if there are any trends related to people who both have rheumatoid arthritis and acupuncture treatment. While the study is observational, they did find that this group of people was less likely to experience a stroke.

The study is available in BMJ Open.

How acupuncture benefits rheumatoid arthritis

While there are a number of treatments available for rheumatoid arthritis, such as JAK inhibitors and corticosteroids, there is not a cure for the disease. There are some things people can do to get some degree of pain relief, though, such as getting massages or having an acupuncture treatment.

Acupuncture is an alternative form of medicine that has origins in traditional Chinese medicine. According to the NIHTrusted Source, it involves “applying small needles or pressure to specific points in the body.”

In addition to helping provide pain relief from rheumatoid arthritis, acupuncture can also treat other types of pain, mood disorders, nausea, and fibromyalgia.

Acupuncture provides relief by causing changes in the central nervous system. The NIHTrusted Source explains that acupuncture “inhibits the expression of pro-inflammatory cytokines (such as TNF-alpha)” and “promotes the expression of anti-inflammatory and tissue-repair factors.”

Since inflammation associated with rheumatoid arthritis factors into people with the disease being at a higher risk for cardiovascular disease, including ischemic strokes, a treatment that interrupts the inflammation process, such as acupuncture, may provide more than standard pain benefits.

To that end, the researchers used data from Taiwan’s Registry for Catastrophic Illness Patients Database for their study to see if there was any correlation between rheumatoid arthritis participants who had acupuncture and outcomes in terms of strokes.

The authors included people in the study who were at least 18 years old, had no disruption in health insurance, and had no history of stroke before the beginning of the study window.

The participant sample included 23,226 people with rheumatoid arthritis who were diagnosed between 1997 and 2010. Of that group, 12,266 underwent an average of 10 acupuncture treatments over the course of about 3 years.

The participant pool was mainly female, and while the researchers included adults of all ages, the 40-59 female age bracket made up the bulk of the participants.

After gathering this information, they next looked at what treatments the participants underwent over the study period as well as any major health events.

Acupuncture and stroke risk 

By the end of the monitoring period, more than 900 participants experienced an ischemic stroke. Ischemic strokes cut off the blood supply to the brain.

Of those participants, 341 people from the acupuncture group had an ischemic stroke. In comparison to the group that didn’t undergo acupuncture treatments, this comes out to a 43% reduced stroke risk.

When the researchers took a closer look at the data to see whether different demographics or medical conditions could factor into these findings, they did not see any evidence of this.

“The advantage of lowering ischaemic stroke incidence through acupuncture therapy in rheumatoid arthritis patients was independent of sex, age, types of drugs used, and comorbidities,” write the authors.

The authors also note that “causality could not be proven directly through our study design … [but it] offers important ideas for more comprehensive research in the future.”

Rheumatoid arthritis heightens heart disease risk

Dr. Rigved Tadwalkar, a board certified consultant cardiologist at Providence Saint John’s Health Center in Santa Monica, California, spoke with Medical News Today about the study.

Dr. Tadwalkar first touched on why rheumatoid arthritis can cause cardiovascular diseases such as strokes.

“Individuals with rheumatoid arthritis (RA) face an elevated risk of cardiovascular disease (CVD) due to several interconnected factors,” said Dr. Tadwalkar. “The chronic inflammation characteristic of RA extends beyond the joints, affecting blood vessels and promoting atherosclerosis.”

“This inflammatory process damages the vessel lining and promotes plaque formation, leading to narrowed arteries and an increased susceptibility to heart attacks and strokes,” Dr. Tadwalkar continued.

Dr. Tadwalkar found the study findings “intriguing.”

“We observe a potential association between acupuncture and a diminished risk of stroke in individuals managing rheumatoid arthritis,” commented Dr. Tadwalkar. “The study implies that acupuncture may play a significant role beyond conventional approaches, potentially influencing the overall health outcomes in this patient population.”

Further research needed before recommending acupuncture

Dr. Tadwalkar said that more research is needed into the benefits of acupuncture and rheumatoid arthritis.

“While it is premature to draw definitive conclusions, these findings prompt further exploration into the integration of alternative therapies in comprehensive strategies for cardiovascular risk reduction in individuals with rheumatoid arthritis,” said Dr. Tadwalkar.

Dr. Cheng-Han Chen, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, California, also spoke with MNT.

Dr. Chen emphasized that this is an observational study and that more research is needed before the findings can be applied at a clinical level.

“These results warrant further study to investigate whether acupuncture may be beneficial for reducing stroke in a wider population,” said Dr. Chen.

“As with all observational studies, this study is not able to determine that acupuncture was causal to the reduction in stroke,” noted Dr. Chen. “In addition, it remains to be determined whether these findings are generalizable to a more ethnically diverse population.”

Is a treatment for those at genetic risk of Alzheimer’s on the horizon?

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Animal research may be bringing us a step closer to new treatments for those genetically predisposed to Alzheimer’s disease.

  • Alzheimer’s disease is the commonest form of dementia, causing up to 70% of the 55 million dementia cases worldwide.
  • Around half of those who develop Alzheimer’s disease have a variant of one gene — APOEe4— that increases the risk of developing the condition.
  • This gene variant prevents cells clearing the beta-amyloid plaques that are characteristic of Alzheimer’s disease.
  • Now, a study in nematodes and mice has identified a molecule that can inhibit APOEe4 and allow the cells to clear these beta-amyloid deposits, and potentially alleviate Alzheimer’s disease symptoms.

With an aging global population, dementia is a growing concern worldwide. A recent forecast by The LancetTrusted Source estimated that the worldwide burden of dementia is set to almost triple by 2050.

Of these dementia cases, according to the World Health Organization (WHO)Trusted Source, 60–70% are due to Alzheimer’s disease.

For dementia, the greatest risk factor is aging — with the likelihood of developing dementia increasing each year from the age of 65Trusted Source.

Genetics can also influence whether a person develops dementia: About 1% of cases of Alzheimer’s disease are entirely caused by genes, and other genes increase the risk of developing Alzheimer’s.

The gene that expresses apolipoprotein ETrusted Source, the APOE gene, influences Alzheimer’s disease risk. One variant, or alleleTrusted Source, of this gene, APOEe4, increases the risk of Alzheimer’s disease, with between 40–65% of people with Alzheimer’s disease having at least one copy of this allele.

Dr. Emer MacSweeney, CEO and medical director at Re:Cognition Health, told Medical News Today:

“In 2018, it was shown those with an APOEe4 gene are less able to clear waste products from the brain and, therefore, more susceptible to building up toxic levels of amyloid and tau protein, which is the hallmark of Alzheimer’s disease. The toxic amyloid and tau protein relentlessly destroy further brain cells, with the progression of the characteristic symptoms of [Alzheimer’s disease].”

Now, a team led by researchers at the University of Arkansas for Medical Sciences have found a molecule that binds to APOEe4and inhibits its harmful effects. They suggest it may form the basis for a new treatment for Alzheimer’s disease with a genetic basis.

The research is published in Communications Biology.

Dr. MacSweeney, who was not involved in the research, welcomed the study.

She said: “This study focuses on the role of the APOE gene, specifically the APOEe4 allele, in Alzheimer’s disease and explores a potential therapeutic strategy using small molecules to target APOEe4. The research combines genetic association studies, cellular mechanism investigations, computational modelling, and experimental validation.”

APOEe4 gene variant linked to amyloid plaques

Studies have shown that APOEe4 has several effects, including disrupting lipid metabolismTrusted Source and driving beta-amyloid pathologyTrusted Source. Both of these can increase the risk of dementia, but for Alzheimer’s disease, beta-amyloid pathology is key.

This latest study found that APOEe4 blocks genes responsible for autophagyTrusted Source — the breakdown and recycling of worn out cell parts and macromolecules in cells. If these genes are inhibited, molecules such as beta-amyloid build up rather than being recycled.

When beta-amyloid builds up it forms plaques on and around nerve cells, which is thought to drive the cognitive impairment and other symptoms that are characteristic of Alzheimer’s disease.

The researchers used in vitro and in vivo models in both Caenorhabditis elegansTrusted Source — a nematode worm widely used in genetic research — and mice.

In molecular models, they first identified the site on DNA where APOEe4 binds to inhibit autophagy. They then investigated molecules that could block this region to prevent APOEe4 binding, allowing autophagy of beta-amyloid to continue.

One molecule — CBA2 — bound to a stable “pocket“ region on APOEe4, blocking its activity.

Dr. Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of Medical and Scientific Relations, not involved in this study, commented on its findings, noting that:

“It is exciting to see advances in technology that may accelerate therapy discovery. And it is exciting that this newly announced research is looking at a novel and understudied therapeutic target — APOEe4 and its actions in the brain. But the research is very preliminary; it is being conducted in mouse and other animal models of Alzheimer’s. We are still far from knowing whether this experimental treatment will be safe and effective in people.”

Molecule inhibits APOEe4 to prevent amyloid build-up

Once the molecule bound to the stable region, it inhibited the gene, as Dr. MacSweeney explained to MNT: “The lead compound, CBA2, is found to selectively bind to this pocket, demonstrating efficacy in restoring autophagic transcription in APOEe4-expressing models, including primary astrocyte cultures and T98G cells.”

In C. elegans nematodes genetically altered to show Alzheimer’s disease-like changes, CBA2 significantly reduced the build up of beta-amyloid, and reversed the decline in chemotaxisTrusted Source, the worms’ response to a chemical stimulus.

When researchers treated the mice modified to express APOEe4, expression of the autophagy genes increased. Dr. MacSweeney told MNT that the results were encouraging, but urged caution.

“In mice with APOEe4, CBA2 boosts the activity of key genes linked to cleaning up harmful substances in the brain, an important part of Alzheimer’s. However, the effects are stronger in mice with APOEe4 than in those with APOEe4,” she explained.

“While these findings are positive, more research and testing in humans are needed to confirm CBA2’s potential benefits for Alzheimer’s,” she added.

Potential new treatment target for those genetically at risk

The researchers suggest that CBA2 might form the basis of treatment to help avoid amyloid build up in people with the gene.

“CBA2, identified as a promising therapeutic compound, demonstrated effectiveness in mitigating APOEe4-associated issues in both worms and mice. If proven safe and effective in humans, CBA2 could represent a targeted treatment to address molecular and behavioural aspects of [Alzheimer’s disease], particularly for individuals carrying the APOEe4 allele.”

– Dr. Emer MacSweeney

Dr. MacSweeney welcomed the findings, saying that “[t]his is the first time a potential compound to specifically block the harmful effects of APOEe4 has been described.”

“These results suggest hope, particularly for the 25% of the population who inherit one copy of the APOEe4 gene and are three times more likely to develop [Alzheimer’s disease] between ages 65-85, than an individual who does not have an APOEe4 gene. And the 2-3% of the population who inherit two APOEe4 genes; these individuals are 12-15 times more likely to develop [Alzheimer’s disease] than the general population,” she told us.

This optimism was echoed by Dr. Snyder, who suggested that targeting APOEe4 might form part of a multifaceted approach to Alzheimer’s disease treatment.

“We know the underlying biology of Alzheimer’s is complex, and therefore that effective treatment is likely going to be a combination approach that will be personalized to each individual,” said Dr. Snyder.

“The Alzheimer’s Association envisions a time in the relatively near future when there are many approved treatments that address Alzheimer’s in multiple ways across the entire course of the disease, and that can be combined into powerful combination therapies that more effectively slow and even stop the disease,” she added.

Fluorescent Test Lights up Amyloids to Diagnose Alzheimer’s, Parkinson’s, and More

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3d illustration of the human brain with visible blood vessels illustrating Alzheimer's disease and dementia, which Biogen is developing treatments for

A fluorescent coumarin-based, two-sensor array correctly discriminates between four different amyloids implicated in amyloid-related pathologies with 100 percent classification, according to research from an Australian team. Their work was published in ACS Sensors, and the lead author is Natalie Trinh of the University of Sydney.

One of the biggest challenges in many neurodegenerative diseases, including Alzheimer’s and Parkinson’s, is early diagnosis. These diseases may present similarly, but require very different treatments, causing delay or confusion about proper treatment.

Amyloids, aggregated self-assembled misfolded proteins, are considered the tell tale markers for some such conditions. Amyloids interrupt signal transfer and there is lot of evidence linking them to the progression of Alzheimer’s disease, so they could be used as a means of early diagnosis to expand treatment options. But early detection has so far been out of reach. 

This test could help monitor disease progression or distinguish between different amyloid-related conditions as well as inform new approaches for earlier and more accurate diagnosis of amyloid-related diseases.

Currently, radioimaging techniques including positron emission tomography (PET) scans can detect amyloids, but these methods rely on sophisticated equipment and typically focus on one of several amyloids involved in the disease. 

Fluorescence imaging techniques are being explored as a simpler, yet still sensitive, means of detecting multiple specific amyloids. This team wanted to develop a fluorescent sensor array for amyloids to monitor Alzheimer’s and other disease progression and to distinguish these atypical amyloids from similar, naturally occurring amyloid-forming proteins.

The team combined five coumarin-based molecular probes, each of which fluoresce to a different degree when it encountered the amyloids, into a sensor array. However, the team found that using just two of the probes with the strongest fluorescence responses offered a high level of sensitivity but accurately identified the individual amyloids.

The two-probe array was added to a sample mixture mimicking biological fluids containing molecules that could potentially interfere with sensing. The array still maintained a high sensitivity and selectivity.

The test’s performance was also tested on samples taken from the brains of mouse models of Alzheimer’s. The team observed that the fluorescence patterns differed between early (at age six months) and later (at age 12 months) stages of the disease. Additionally, a unique fluorescence fingerprint was generated for three amyloids typically involved in Alzheimer’s, another disease-associated amyloid and five naturally occurring “functional amyloids” not involved in the disease. 

The flexibility of the array was assessed by expanding the analytes to include functional amyloids. The same two-sensor array correctly discriminated between eight different disease-associated and functional amyloids with 100 percent classification.

The authors conclude, “These results demonstrate the utility of our fluorescent sensing array for the detection of amyloids implicated in Alzheimer’s disease and the potential it holds as a tool for researchers investigating functional amyloids, such as hydrophobins.”

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

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Abstract

Cancer treatment remains a significant challenge due to issues such as acquired resistance to conventional therapies and the occurrence of adverse treatment-related toxicities. In recent years, researchers have turned their attention to the microbial world in search of novel and effective drugs to combat this devastating disease. Microbial derived secondary metabolites have proven to be a valuable source of biologically active compounds, which exhibit diverse functions and have demonstrated potential as treatments for various human diseases. The exploration of these compounds has provided valuable insights into their mechanisms of action against cancer cells. In-depth studies have been conducted on clinically established microbial metabolites, unraveling their anticancer properties, and shedding light on their therapeutic potential. This review aims to comprehensively examine the anticancer mechanisms of these established microbial metabolites. Additionally, it highlights the emerging therapies derived from these metabolites, offering a glimpse into the immense potential they hold for anticancer drug discovery. Furthermore, this review delves into approved treatments and major drug candidates currently undergoing clinical trials, focusing on specific molecular targets. It also addresses the challenges and issues encountered in the field of anticancer drug research and development. It also presents a comprehensive exposition of the contemporary panorama concerning microbial metabolites serving as a reservoir for anticancer agents, thereby illuminating their auspicious prospects and the prospect of forthcoming strides in the domain of cancer therapeutics.

Conclusions and future perspectives

Balancing the effectiveness of cancer treatments with potential side effects presents a significant challenge in cancer therapeutics. Some well-established microbial metabolites, such as doxorubicin and bleomycin, have demonstrated strong abilities to kill cancer cells and are routinely used in cancer treatment plans. These well-established, microbial-derived compounds are often accompanied by severe adverse toxicities. Due to these toxicities, treatment with the compound is often shortened or stopped, or the dosage is lowered to where it becomes significantly less effective in reducing the patient’s disease progression. A solution to these shortcomings with the current microbial-based treatment modalities has been a refocusing towards microbial-based anticancer agents with a high degree of cancer specificity.

Given that these compounds originate from microorganisms there may be good reason for utilizing them for cancer treatment by modulating the immune system. The innate immune system can be engaged by metabolites through pattern recognition receptors that act as sensors, for shared patterns found in microbes. When these receptors are activated, they can trigger a response leading to the activation of antigen-presenting cells and the production of inflammatory and effector cytokines. In the context of cancer, this response can alert the system to the presence of a tumor. Potentially contribute to its elimination. These compounds exhibit a remarkable feature – they contain components that can stimulate the immune system. This immunostimulatory property enables them to precisely target cancerous tissues, leaving healthy tissues unaffected.

Similarly, the selectivity of the immune system can also be utilized in the context of antibody-drug conjugates incorporating microbial metabolites as a “warhead” molecule. In this context, a highly and non-selectively cytotoxic microbial metabolite would be conjugated to a monoclonal antibody. To selectively target cancer cells, the antibody is specific for moieties expressed only on malignant cells. As a result, the cytotoxic compound is solely delivered to cancerous cells, leading to highly selective cancer cell death. These compounds have already demonstrated clinical efficacy and will likely be further developed through incorporation of novel tumor antigen targets and microbial metabolites with greater potency.

This exciting generation of secondary metabolites represents just a fraction of the bioactive compounds found in the microbial world that hold potential for treating human diseases, including cancer.

Invasive meningococcal disease risk sixfold higher for people with HIV

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Key takeaways:

  • Between 2009 and 2019, people with HIV had a sixfold higher risk of invasive meningococcal disease.
  • Many people with HIV (50%) had not received the recommended MenACWY vaccine.

People with HIV continue to have a higher risk for invasive meningococcal disease compared with people without HIV regardless of the 2016 recommendation that they be vaccinated against it.

“This analysis was a follow-up to a previous evaluation of invasive meningococcal disease (IMD) risk in persons with HIV to better understand how the declining incidence of IMD in the U.S., along with the 2016 Advisory Committee on Immunization Practices MenACWY recommendation for people with HIV, has affected IMD risk in people with HIV,” Gabrielle Cooper, DrPH, MPH, epidemiologist at the CDC’s National Center for Immunization and Respiratory Diseases, told Healio.

IDN0224Rudmann_Graphic_01_WEB
Data derived from Rudmann KC, et al. Open Forum Infect Dis. 2024;doi:10.1093/ofid/ofad696.

To better understand the incidence of IMD and how the 2016 routine quadrivalent meningococcal conjugate vaccine recommended for people with HIV has affected IMD risk, Cooper and colleagues evaluated cases of IMD reported between 2009 and 2019 within the Active Bacterial Core surveillance area among patients aged 13 and older. In total, 636 cases were reported — 16 of which were among people with HIV.

After comparing the incidence of IMD in people with HIV and people without HIV between 2009 and 2019, data showed a sixfold higher IMD risk among people with HIV vs. those without (0.96 vs. 0.16 cases per 100,000).

According to the study, most people with HIV had not received the MenACWY vaccine (50%) or had an unknown vaccination history (43.8%), with only one patient (6.3%) reporting previous MenACWY vaccination.

Additionally, five (31.3%) of the cases occurred after the 2016 ACIP recommendation for routine MenACWY vaccination in people with HIV. Of those five, four (80%) were unvaccinated and one (20%) had an unknown vaccination history.

“As persons with HIV continue to experience increased IMD risk, there is a growing importance of improving implementation of the ACIP MenACWY vaccine recommendation for people with HIV,” Cooper said. “There is also need for continued monitoring of IMD in people with HIV.”

Perspective

Susan Kline, MD, MPH

This article reports the analysis of the CDC’s Active Bacterial Core surveillance data regarding invasive meningococcal disease from 2009-2019. Of note the authors found a sixfold increase in the risk for invasive meningococcal disease in persons living with HIV compared with those without HIV infection.

Despite the relatively new availability of a quadrivalent meningococcal vaccine, and the 2016 US ACIP recommendation for routine quadrivalent meningococcal conjugate vaccination among persons with HIV infection, ages 2 months and up, there remain many unvaccinated persons living with HIV. The mortality rate of invasive meningococcal disease in this study was 18.8% in persons living with HIV, and a majority were still unvaccinated.

There remains a large opportunity to immunize many more persons living with HIV with the new quadrivalent meningococcal vaccine. Doctors providing medical care to persons living with HIV should focus efforts on encouraging their patients to take the available quadrivalent MenACWY meningococcal vaccine because these patients have a sixfold higher risk for invasive meningococcal disease than those not infected with HIV and because mortality from invasive meningococcal disease is still high (approximately 20%).

Susan Kline, MD, MPH

Professor of medicine, Infectious Disease Division

University of Minnesota Medical School

Why Walking, Yoga, and Strength Training May Help Ease Depression.

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New research finds that simple exercises like walking, jogging, yoga, and strength training can help ease symptoms of depression.

  • A review of 218 scientific trials has found that walking, jogging, yoga, and strength training may be the most effective exercises for relieving symptoms of depression.
  • The more vigorous the exercise, the greater the mental health benefits are likely to be.
  • Experts say this is likely due to the release of feel-good hormones, engagement in a routine, and the social interaction exercise often provides.
  • It can be difficult to exercise when you’re depressed, so experts recommend starting slow and finding something you enjoy.

Have you ever noticed that your mood improves when you exercise?

New research has found that certain kinds of exercise – specifically walking, jogging, yoga, and strength training – seem to be the most effective at easing symptoms of depression.

The research published in The BMJ found that these exercises were effective at reducing depression when used alone or alongside established treatments such as psychotherapy and medication.

Furthermore, the results suggest that, while low intensity exercise is beneficial, the more vigorous the activity, the greater the benefits are likely to be.

To assess the existing data, the study authors reviewed 218 relevant trials involving 14,170 participants that compared exercise as a treatment for depression with established treatments, like antidepressants and cognitive behavioral therapy.

Moderate reductions in depression were found in walking or jogging, yoga, strength training, mixed aerobic exercises, and tai chi or qi gong.

Moderate effects were also found when exercise was combined with SSRI antidepressants or aerobic exercise was combined with psychotherapy, which suggests that exercise could provide added benefit alongside these established treatments.

While the authors acknowledge that the quality of evidence is low and very few trials monitored participants for one year or more, they say the results suggest that these forms of exercise “could be considered alongside psychotherapy and drugs as core treatments for depression.”

In particular, they note that a combination of social interaction, mindfulness, and immersion in green spaces may help explain the positive effects.

The link between exercise and mental health

Clinical psychologist Charlotte Russell, who was not involved int the study, isn’t surprised by these findings and says there are likely several mechanisms that explain the effect exercise has on mood.

One of these is the impact of neurochemicals, including dopamine, serotonin, and endorphins, which are released when we exercise.

Serotonin stabilizes mood, dopamine contributes to feelings of happiness, and endorphins can provide a natural high.

Additionally, Russell says exercise can provide a sense of meaning and engagement in routine. There is often a social element as well, and all of these factors can positively influence our mental health.

“Building exercise into your routine also breaks the cycle of worsening mood and decreased activity that we commonly see in depression,” Russell adds.

“When we are inactive and not using our body, this can contribute to a sense of sluggishness and low motivation, which can quickly lead to a downward spiral. Regular exercise breaks this and maintains a sense of well-being,” she explains.

How different kinds of exercise can affect depression

You might be wondering why walking, jogging, yoga, and strength training appear to be particularly effective at relieving symptoms of depression.

With walking and jogging, Russell says the benefits may lie in the fact that these exercises are often done outside.

“This typically offers a feeling of connection with nature, and we know that this can be beneficial for us psychologically,” she explains.

Yoga, meanwhile, teaches you to focus on your breathing, something Russell says can lessen feelings of anxiety and create an awareness of our internal state.

“The latter is a skill that can be very beneficial in terms of managing difficult thoughts and feelings,” she notes.

What about the benefits of strength training?

Russell says strength training can help you feel stronger in your body and allow you to complete everyday tasks more easily.

“This has a protective effect on our sense of self and mood,” she notes.

Why does vigorous exercise seem to be best?

Clinical hypnotherapist and wellness coach Geraldine Joaquim, who was not involved in the study, says the more vigorous the exercise, the more you’ll feel those high-achievement hormones, which can have a huge internal effect.

But, she says, taking things at your own pace is more important.

How to safely get started with a new exercise routine

If you live with depression, it isn’t always easy to find your get-up-and-go.

“It takes more effort to move forward when you’re depressed because you’re on an uphill battle to create hormonal activity,” Joaquim explains.

“That’s why it’s important to start where you are and build slowly. That might mean simply putting trainers on and walking to the end of your garden. Doing it again. And again. Then expanding, going to the end of the road, for example.”

By working slowly and being kind to yourself, Joaquim says you are gently promoting the production and release of hormones like serotonin, dopamine, and oxytocin that make you feel good.

Joaquim advises aiming for around 80% of your capacity rather than going all out and exhausting yourself if you’re not sure how much is too much when you’re exercising.

“Notice what’s happening in your body as you move, enjoy the feelings of stretching muscles, deep breathing, and feeling strong – and remember, nothing is set in stone. You can change what you’re doing at any time,” she notes.

Meanwhile, Russell points out that many gyms and fitness studios offer classes and exercise courses that are suitable for beginners.

“Choosing this option can be reassuring for many as everyone will be in a similar situation,” she says. “However, if an in-person class seems too daunting, start with an online class to build your confidence.”

Takeaway

Exercising when you are depressed can be challenging, and taking the initiative to move can be daunting.

However, research shows, finding ways to move your body is vital for good mental health.

Even low intensity movement can help.

“The more you feel able to do, the more you want to do. It’s a positive spiral that has real physical changes,” says Joaquim.

Scientists Found 5 Factors to Improve Brain Health and Lower Dementia Risk

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Doctors say they may even be more helpful than medicine.

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  • New research links certain healthy habits to a sharper brain as you age.
  • The study followed participants for more than two decades.
  • Doctors say these are good habits to follow for brain and overall health.

There’s a general recipe for living well that includes regular physical activity, eating a healthy diet, and avoiding smoking. Now, new research finds five factors that can also help support brain health and sharp thinking as you age,

The study, which was published in JAMA Neurology, looked at the autopsies of 586 people who lived to an average age of 91. Those study participants participated in the Rush Memory and Aging Project before their deaths, which involved them undergoing regular mental and physical tests, along with annual questionnaires on their lifestyles for more than 20 years.

The researchers found a direct link between healthy lifestyle habits and a lowered risk of cognitive decline as the participants got older—that was true, even in people who had hallmark signs of developing Alzheimer’s disease or dementia. Lead study author Klodian Dhana, M.D., Ph.D., an assistant professor of geriatrics and palliative medicine at the Rush Institute for Healthy Aging, says his team wanted to see if certain factors could influence whether someone develops Alzheimer’s or dementia. “As individuals age, there is a progressive accumulation of dementia-related brain pathologies,” he says. However, not everyone goes on to develop dementia, despite these changes in the brain. The goal of the study, Dr. Dhana says, was to see if lifestyle factors would make a difference in how likely someone is to develop dementia.

Here’s what Dr. Dhana and his team discovered.

Factors to improve brain health

The study participants were labeled as having a low-risk or healthy lifestyle if they did the following:

  • No smoking.
  • Doing moderate to vigorous exercise for at least 150 minutes a week.
  • Limit alcohol use to one drink a day for women and two drinks a day for men.
  • Engage in brain-stimulating activities, like reading, playing games, and visiting museums.
  • Follow a variation of the MIND diet.

Study participants received a healthy lifestyle score within these areas and, the healthier they were, the better their brain health. The researchers found that for every one-point increase in the healthy lifestyle score, the lower the amount of beta-amyloid plaques (hallmarks of Alzheimer’s disease) and the higher their score on cognitive tests that looked at factors like memory and attention span.

An editorial that was published alongside the study pointed out that the benefits of following these healthy lifestyle factors were still there, regardless of whether the study participants had signs of dementia and Alzheimer’s disease in their brains.

Why are these habits good for the brain?

At baseline, these lifestyle factors and habits are known to be good for you. “Following a healthy lifestyle is good for the brain,” says Amit Sachdev, M.D., M.S., medical director in the Department of Neurology at Michigan State University.

These factors in particular “have been investigated and shown to be associated with slower cognitive decline and a lower risk of dementia,” Dr. Dhana says.

While plant-based diets have been linked to healthier brains, the MIND diet is a specific kind of plant-based diet. It incorporates several elements of the Mediterranean diet, like plenty of fruits, vegetables, nuts, beans, olive oil, and whole grains, explains Jessica Cording, M.S., R.D., author of The Little Book of Game-Changers: 50 Healthy Habits For Managing Stress & Anxiety.

“Previous studies on similar diet patterns have shown that this style of eating is very rich in polyphenols, which are powerful plant compounds that have been shown to have neuroprotective properties,” Cording says. “That’s a big piece of the puzzle.” The foods featured in this diet can help tamp down on bodily inflammation and promote good gut and heart health, she points out.

That diet, along with regular exercise, limiting alcohol use, and avoiding smoking is good for the cardiovascular system, Cording says. “What’s good for the heart and blood vessels is generally good for the brain—we have tons of blood vessels in the brain,” she says.

Clifford Segil, D.O., a neurologist at Providence Saint John’s Health Center in Santa Monica, CA., agrees. “A healthy lifestyle increases your heart health and brain health,” he says. “A healthy heart can only help your brain.”

Research has also found that doing mentally stimulating activities is linked with a lowered risk of developing dementia. “The thing I most often recommend to patients for their brain health is structured cognitive exercise,” Dr. Segil says. “That can mean taking a class at a junior college. With muscles, if you don’t use it, you lose it. The same is true of your brain.”

Dr. Segil stresses the importance of healthy lifestyle habits for brain health, noting that he sees patients do better after making lifestyle tweaks than they do taking certain medications to lower the risk of cognitive decline.

Overall, Dr. Dhana says the lifestyle factors laid out in his study may help provide cognitive benefits over time. But, if you’re concerned about your own risk of dementia or have a family history of the disease, he recommends seeing a doctor for personalized recommendations.

Does Viagra reduce the risk of Alzheimer’s? Here’s what we know.

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Viagra is best known for triggering erections, but several studies have suggested that the drug may lower the risk of Alzheimer’s disease. What do we know so far.

Numerous studies have suggested that erectile-dysfunction drugs like Viagra, the famous “blue pill,” may reduce someone’s risk of developing Alzheimer’s. But so far, none have proved that the drugs actually cause that risk reduction. (Image credit: Bloomberg / Contributor via Getty Images)

Drugs taken to treat erectile dysfunction have once again been tied to a reduced risk of Alzheimer’s disease. 

A new study of almost 670,000 men in the U.K., published Feb. 7 in the journal Neurology, revealed that those who take so-called phosphodiesterase 5 inhibitors (PDE5I) — which include Viagra (generic name sildenafil) — may have a lower risk of developing this common form of dementia than men of the same age who don’t take the drugs. 

This isn’t the first time that drugs like the “little blue pill” have been linked to this reduced dementia risk. Since the late 1990s, rodent studies have suggested that PDE5I drugs could have beneficial effects on cognition, and in 2021, a study published in the journal Nature Aging suggested that taking Viagra was associated with a 69% reduced risk of Alzheimer’s. That 2021 study included more than 7 million people in the U.S. who on average were around 71 years old, 116,000 of whom took Viagra. 

PDE5I drugs like Viagra work by increasing blood flow to the erectile tissues of the penis. They do this by preventing the breakdown of a signaling molecule called cyclic guanosine monophosphate (cGMP), which keeps smooth muscles within the penis relaxed. This relaxation allows blood to flow into the erectile tissue — the corpus cavernosum — as its blood vessels dilate upon sexual arousal. When cGMP gets broken down too quickly, the erection can’t be maintained. 

Related: Viagra alternatives? Study of mouse erections hints at new ways to treat erectile dysfunction

While Viagra’s effects on the penis are well understood, it’s unknown how this and similar drugs may influence brain disorders such as Alzheimer’s. However, several potential mechanisms have been proposed. 

Other than influencing erections in the penis, PDE5I drugs dilate blood vessels throughout the body, including in the brain, Dr. Sevil Yasar, an associate professor of medicine at Johns Hopkins University, told Live Science. Indeed, Viagra was originally developed to treat high blood pressure and chest pain. It’s therefore possible that increased blood flow in the brain may somehow reduce the burden of Alzheimer’s, she said. 

In the 2021 Nature Aging study, Feixiong Cheng, a principal investigator at the Cleveland Clinic, and colleagues found that Viagra boosted the growth of brain cells that had been grown from the stem cells of patients with Alzheimer’s. The drug also turned down the production of proteins associated with the disease — namely, phosphorylated tau, which accumulates in the brains of people with Alzheimer’s. 

Increased blood flow to the brain that results from these drugs might therefore help clear these proteins in some way, Cheng told Live Science. 

Another explanation could be that PDE5I drugs strengthen the connections, or synapses, between neurons in the brain, as this process partially relies on cGMP, Atticus Hainsworth, a reader in cerebrovascular disease at St George’s, University of London, told Live Science. The brain stores memories by strengthening synapses, helping linked neurons “talk” to one another. This could explain the link between PDE5I drugs and a reduced risk of Alzheimer’s, which causes memory loss.

In addition, people with high blood pressure or type 2 diabetes have a higher risk of experiencing erectile dysfunction and of developing Alzheimer’s, compared with people without either condition. So it could be that erectile-dysfunction drugs are helping to manage these other conditions, rather than directly targeting the causes of Alzheimer’s, Yasar said. 

For now, though, none of these theories has been definitively proved — in fact, it’s still unclear whether PDE5I drugs have any effect on Alzheimer’s risk. 

In 2022, for example, a study in people with pulmonary arterial hypertension — a form of high blood pressure in the lungs that can be treated with PDE5I drugs — found that the medications were not associated with a reduced risk of Alzheimer’s. 

A big issue is that the largest studies to date have been observational, meaning they retroactively compared the rates of disease between different people without accounting for other factors that could affect people’s Alzheimer’s risk. Such studies can’t definitely prove that erectile-dysfunction drugs influence the risk.

Medical illustration of a synapse between two neurons. The neurons are in blue and the synapse between them illuminated in gold against a dark background
Phosphodiesterase 5 inhibitors may lower a person’s Alzheimer’s risk by strengthening the connections, or synapses (illustrated here), between neurons in the brain.  (Image credit: ARTUR PLAWGO / SCIENCE PHOTO LIBRARY via Getty Images)

To do so, scientists would need to conduct a gold-standard clinical trial with comparison groups who don’t take the drug but are matched to those who do in other ways, such as age and sex. This would help ensure that other lifestyle factors or medical conditions don’t skew the results. 

For example, “it could be that the people who are still cognitively well enough to have sex and want the drugs are biasing the [study] population,” Hainsworth said. 

A few clinical trials have assessed the potential cognitive effects of PDE5I drugs in humans. However, these have been limited in size; one trial included only 10 people, for instance. Some have tested only the short-term impacts of the treatment — for example, with the cognitive effects of a single dose measured over the course of a day.  

To get closer to proving that erectile-dysfunction drugs can help prevent Alzheimer’s, future trials would need to run for potentially three to five years and include people with clinically confirmed Alzheimer’s diagnoses, Yasar said. This would go beyond relying on, say, insurance claims data, as previous observational studies have done, she said. 

It would also be important to look for telltale markers of Alzheimer’s disease during the trials, using brain imaging to measure changes in a person’s blood flow after they took PDE5I drugs, she added. 

Long-term trials would allow scientists to look out for any long-term side effects of taking erectile-dysfunction drugs. Such side effects could stem from taking a drug that reduces the pressure of blood flowing through your arteries, Francesco Tamagnini, a lecturer in pharmacology at the University of Reading in the U.K., told Live Science. 

On a mechanistic level, the drugs may need to be modified slightly so they are more likely to accumulate in the brain, to achieve the most robust effects, Tamagnini said. 

Future trials could also include women, as well as men, to see if similar cognitive effects are seen in them, Hainsworth said. Currently, Viagra is only approved by the U.S. Food and Drug Administration (FDA) to treat erectile dysfunction in men. Several early studies have investigated whether it could be used to treat sexual dysfunction in women, but with conflicting conclusions about effectiveness. 

If these drugs eventually turn out to be an effective guard against Alzheimer’s, they could fuel the fire of research striving to repurpose approved drugs for other uses. This is happening with the diabetes drug metformin, for example, which doctors are trying to repurpose for cancer and heart disease, Tamagnini said. As these drugs are already licensed for use in humans, this could speed up the drug-development process, he said. 

For the little blue pill, though, there’s a long way to go before it would be prescribed as dementia prevention.

New chip opens door to AI computing at light speed.

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University of Pennsylvania engineers have developed a new chip that uses light waves, rather than electricity, to perform the complex math essential to training AI. The chip has the potential to radically accelerate the processing speed of computers while also reducing their energy consumption.

The silicon-photonic (SiPh) chip’s design is the first to bring together Benjamin Franklin Medal Laureate and H. Nedwill Ramsey Professor Nader Engheta’s pioneering research in manipulating materials at the nanoscale to perform mathematical computations using light—the fastest possible means of communication—with the SiPh platform, which uses silicon, the cheap, abundant element used to mass-produce computer chips.

The interaction of light waves with matter represents one possible avenue for developing computers that supersede the limitations of today’s chips, which are essentially based on the same principles as chips from the earliest days of the computing revolution in the 1960s.

In a paper appearing in Nature Photonics, Engheta’s group, together with that of Firooz Aflatouni, Associate Professor in Electrical and Systems Engineering, describes the development of the new chip.

“We decided to join forces,” says Engheta, leveraging the fact that Aflatouni’s research group has pioneered nanoscale silicon devices.

Their goal was to develop a platform for performing what is known as vector-matrix multiplication, a core mathematical operation in the development and function of neural networks, the computer architecture that powers today’s AI tools.

Instead of using a silicon wafer of uniform height, explains Engheta, “you make the silicon thinner, say 150 nanometers,” but only in specific regions. Those variations in height—without the addition of any other materials—provide a means of controlling the propagation of light through the chip, since the variations in height can be distributed to cause light to scatter in specific patterns, allowing the chip to perform mathematical calculations at the speed of light.

Due to the constraints imposed by the commercial foundry that produced the chips, Aflatouni says, this design is already ready for commercial applications, and could potentially be adapted for use in graphics processing units (GPUs), the demand for which has skyrocketed with the widespread interest in developing new AI systems.

“They can adopt the Silicon Photonics platform as an add-on,” says Aflatouni, “and then you could speed up training and classification.”

In addition to faster speed and less energy consumption, Engheta and Aflatouni’s chip has privacy advantages: Because many computations can happen simultaneously, there will be no need to store sensitive information in a computer’s working memory, rendering a future computer powered by such technology virtually unhackable.

“No one can hack into a non-existing memory to access your information,” says Aflatouni.

Other co-authors include Vahid Nikkhah, Ali Pirmoradi, Farshid Ashtiani and Brian Edwards of Penn Engineering.