Publisher Health

Gel-like materials that can be injected into the body hold great potential to heal injured tissues or manufacture entirely new tissues. Many researchers are working to develop these hydrogels for biomedical uses, but so far very few have made it into the clinic.
To help guide in the development of such materials, which are made from microscale building blocks akin to squishy LEGOs, MIT and Harvard University researchers have created a set of computational models to predict the material’s structure, mechanical properties, and functional performance outcomes. The researchers hope that their new framework could make it easier to design materials that can be injected for different types of applications, which until now has been mainly a trial-and-error process.
“It’s really exciting from a material standpoint and from a clinical application standpoint,” says Ellen Roche, an associate professor of mechanical engineering, a member of the Institute for Medical Engineering and Science at MIT, and an author of the paper. “More broadly, it’s a nice example of taking lab-based data and synthesizing it into something usable that can give you predictive guidelines that could be applied to things beyond these hydrogels.”
Jennifer Lewis, the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard, is the senior author of the study, which appears today in the journal Matter. Connor Verheyen, a graduate student in the Harvard-MIT Program in Health Sciences and Technology, is the lead author of the paper.
Material modeling
When individual hydrogel blocks are densely compacted together, they form a gel-like material known as a granular matrix. These materials can act as a solid or a liquid, depending on the conditions, which makes them good candidates for applications such as 3D-bioprinting engineered tissues. Once injected or implanted into the body, they could release drugs or help to regenerate injured tissue.

“These materials have a lot of flexibility and customizability, so there’s a lot of excitement about using them for biomedical applications,” Verheyen says.
While working in Lewis’ lab, Verheyen, who is co-advised by Lewis and Roche, began trying to figure out how to get these materials to be reliably injectable. This turned out to be a difficult task that required a lot of trial-and-error experimentation, by changing different features of the gels in hopes of optimizing their structure and mechanical behavior for injectability.
“That spurred the effort to take the empirical data, turn it into something that a machine could read and work with, and then ask it to build a predictive map that we could interrogate to help us understand what was going on and how to go to the next step,” he says.
To create their design framework, the researchers broke the assembly process down into several stages. They modeled each of these stages separately, using data from their own experiments, which were done under a variety of different conditions.
In the first stage, the model analyzed how bioblock properties are affected by the starting material of the blocks and how they are assembled. In the second stage, the bioblocks are packed together to form structures called “granular hydrogels.” Through their modeling, the researchers identified several factors that influence the injectability of the final gel, including the size and stiffness of the bioblocks, the viscosity of the interstitial fluid between the blocks, and the dimensions of the needle and syringe used to inject the gel.

Better injectability
Now that they have modeled the process from start to finish, the researchers can use their model to predict the best way to create a material with the traits they need for a particular application, instead of going through an extensive trial-and-error process for each new material.
“Our long-term goal was to get to the point where we had reliable and predictable injection properties, because that was something that we really struggled with in the lab — getting these materials to flow properly,” Verheyen says.
He and others in Roche’s lab now plan to use this modeling approach to try to develop materials that could be used for medical applications such as repairing heart defects or delivering drugs to the gastrointestinal tract.
The researchers have also made their models and the data they used to generate them available online for other labs to use.
“It’s all open source, and hopefully it will reduce the amount of frustration with issues that you might have reproducing something that happened in another lab, or even within one lab when you’re transferring knowledge from one person to another,” Roche says.
The research was funded by the Vannevar Bush Faculty Fellowship Program, the National Science Foundation, and a MathWorks Seed Fund grant.

A new vaccine from the University of Georgia could be the first clinically approved immunization to protect against invasive fungal infections, a growing concern as antifungal drug resistance increases.
Fungal infections cause more than 1.5 million deaths worldwide each year and cost billions. They also double hospitalization costs, double the length of hospital stays and double the risk of death in hospitalized patients, according to a previous UGA study.
But there currently are no effective vaccines to protect vulnerable patients from fungal infections.
“There’s a significant unmet clinical need for this kind of prevention and also treatment, particularly among immunocompromised individuals,” said Karen Norris, lead investigator on the new study and professor in the College of Veterinary Medicine. “The patient population at risk for invasive fungal infections has increased significantly over the last several years.”
The experimental vaccine is designed to protect against the three most common fungal pathogens that are responsible for more than 80% of fatal fungal infections. The study tested the vaccine’s efficacy in four preclinical animal models, including nonhuman primates.
The researchers relied on different immunosuppressed models for the study, reflecting drug regimens similar to those of transplant recipients, people with HIV or cancer patients, some of the most at-risk human populations.

The vaccine was effective in developing protective antibodies in each of the models.
“Because it targets three different pathogens, the vaccine has the potential to be groundbreaking regarding invasive fungal infections,” said Norris, who is also faculty in the university’s Center for Vaccines and Immunology. “Plans are underway to develop the vaccine for a Phase I (human) safety trial.”
More people at risk of fungal infections than just immunocompromised
Fungal infections are most commonly seen in people with immune disorders, including those with uncontrolled HIV or impaired immunity from therapies like chemotherapy or anti-inflammatories.
But previous research from Norris, postdoctoral fellow Emily Rayens and the College of Public Health’s José Cordero in 2022 showed that at-risk population has expanded in recent years.

That study showed people with diabetes; chronic obstructive pulmonary disease (or COPD); or co-infections such as COVID-19, tuberculosis or flu are likewise at higher risk of developing fungal infections.
The first line of defense is typically treatment with azoles, which are broad-spectrum anti-fungal medications. But antifungal resistance is growing. As a result, fungal infections are becoming more difficult to treat, making prevention even more critical, Norris said.
The new vaccine targets the three most common causes of fungal infections: Aspergillus, Candida and Pneumocystis. Candida, in particular, is a growing concern in health care circles as different strains of the fungus become multidrug resistant.
The vaccine showed broad, cross-protective antifungal immunity in the animal models, which bodes well for future clinical trials.
“This is an area that has been underdeveloped on the research front for a long time,” said Norris, who is also the Georgia Research Alliance Eminent Scholar in Immunology and Translational Biomedicine. “These are very large populations of people who are at risk of invasive fungal infections, and although there has been considerable efforts to develop vaccines, none are yet approved. We believe this is a very strong vaccine candidate.”
Published in PNAS Nexus, the study was co-authored by the College of Veterinary Medicine’s Emily Rayens, Whitney Rabacal, Hubertine Willems, Gabrielle Kirton, James Barber and Jarrod Mousa; and the Franklin College of Arts and Sciences’ Brandi Celia-Sanchez and Michelle Momany.
This research was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Georgia Research Alliance and the University of Georgia Research Foundation.

Women are disproportionately affected by migraine, especially during their reproductive years. However, the relationship between migraine and adverse pregnancy outcomes has not been well understood. A new study by investigators from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, analyzed data from thousands of women from the Nurses’ Health Study II to assess the relationship between migraine and pregnancy complications. In a paper published in Neurology, the team reports that migraine diagnosed prior to pregnancy was linked to adverse outcomes during pregnancy, including preterm delivery, gestational hypertension, and preeclampsia, suggesting that migraine may be a clinical marker of elevated obstetric risk.
“Preterm delivery and hypertensive disorders are some of the primary drivers of maternal and infant morbidity and mortality,” said first author Alexandra Purdue-Smithe, PhD, associate epidemiologist at Brigham and Women’s Hospital and instructor in Medicine at Harvard Medical School. “Our findings suggest that a history of migraine warrants consideration as an important risk factor for these complications and could be useful in flagging women who may benefit from enhanced monitoring during pregnancy.”
Women are two to three times more likely than men to experience migraine in their lifetime, and migraine is most prevalent among women between the ages of 18 and 44. For some, the migraine headaches can be accompanied by aura (5.5% of the population), which are usually visual disturbances that appear prior to headache onset.
Adverse pregnancy outcomes and migraine, especially migraine with aura, are each consistently associated with higher risk of coronary heart disease and ischemic stroke in women according to prior studies. The underlying biology responsible for these risks might also increase the likelihood of pregnancy complications. But to date, only a few small or retrospective studies have examined migraine as a risk factor for pregnancy complications. No prospective studies have examined risks by aura phenotype (migraine with versus without aura).
Purdue-Smithe and colleagues analyzed data from the large, prospective Nurses’ Health Study II, which included 30,555 pregnancies from 19,694 U.S. nurses. Investigators looked at pre-pregnancy self-reported physician-diagnosed migraine and migraine phenotype (migraine with and without aura) and incidence of self-reported pregnancy outcomes.
Due to the large size of the study population and availability of data on other health and behavioral factors, researchers could control for potential confounding factors in their analyses, such as body mass index, chronic hypertension, and smoking.
Researchers found that pre-pregnancy migraine was associated with a 17 percent higher risk of preterm delivery, 28 percent higher rate of gestational hypertension, and 40 percent higher rate of preeclampsia compared to no migraine. Migraine with aura was associated with a somewhat higher risk of preeclampsia than migraine without aura. Migraine was not associated with low birth weight or gestational diabetes mellitus.
Participants with migraine who reported regular aspirin use (more than twice weekly) prior to pregnancy had a 45 percent lower risk for preterm delivery. The US Preventive Services Task Force currently recommends low-dose aspirin during pregnancy for individuals at high risk of preeclampsia and those who have more than one moderate risk factor for preeclampsia. Clinical trials have shown that low-dose aspirin during pregnancy is also effective at reducing rates of preterm birth. However, Purdue-Smithe notes that migraine is currently not included among indications for aspirin use in pregnancy. “Our findings of reduced risk of preterm delivery among women with migraine who reported regular aspirin use prior to pregnancy suggests that aspirin may also be beneficial for women with migraine. Given the observational nature of our study, and the lack of detailed information on aspirin dosage available in the cohort, clinical trials will be needed to definitively answer this question.”
Some other limitations of the study include that, participants only reported if they had a physician-diagnosis of migraine, likely excluding those who did not have chronic or severe migraine. Further, aura was assessed after the migraine diagnosis and after many of the pregnancies in the cohort, possibly resulting in some degree of reverse causation in analyses examining migraine phenotype. Additionally, the cohort study consists of predominantly non-Hispanic white individuals with relatively high socioeconomic status and health literacy, which could limit generalizability.

A new way to significantly increase the potency of almost any vaccine has been developed by researchers from the International Institute for Nanotechnology (IIN) at Northwestern University. The scientists used chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine, greatly increasing vaccine performance. The antigen targets the immune system, and the adjuvant is a stimulator that increases the effectiveness of the antigen.
The scientists used chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine, greatly increasing vaccine performance. The antigen targets the immune system, and the adjuvant is a stimulator that increases the effectiveness of the antigen.
The study will be published Jan. 30 in Nature Biomedical Engineering.
“The work shows that vaccine structure and not just the components is a critical factor in determining vaccine efficacy,” said lead investigator Chad A. Mirkin, director of the IIN. “Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it.
Mirkin also is the George B. Rathmann Professor of Chemistry at the Weinberg College of Arts and Sciences and a professor of medicine at Northwestern University Feinberg School of Medicine.
This new heightened emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which historically have not worked well, Mirkin said.

Mirkin’s team has studied the effect of vaccine structure in the context of seven different types of cancer to date, including triple-negative breast cancer, papillomavirus-induced cervical cancer, melanoma, colon cancer and prostate cancer to determine the most effective architecture to treat each disease.
Conventional vaccines take a blender approach
With most conventional vaccines, the antigen and the adjuvant are blended and injected into a patient. There is no control over the vaccine structure, and, consequently, limited control over the trafficking and processing of the vaccine components. Thus, there is no control over how well the vaccine works.
“A challenge with conventional vaccines is that out of that blended mish mosh, an immune cell might pick up 50 antigens and one adjuvant or one antigen and 50 adjuvants,” said study author and former Northwestern postdoctoral associate Michelle Teplensky, who is now an assistant professor at Boston University. “But there must be an optimum ratio of each that would maximize the vaccine’s effectiveness.”
Enter SNAs (spherical nucleic acids), which are the structural platform — invented and developed by Mirkin — used in this new class of modular vaccines. SNAs allow scientists to pinpoint exactly how many antigens and adjuvants are being delivered to cells. SNAs also enable scientists to tailor how these vaccine components are presented, and the rate at which they are processed. Such structural considerations, which greatly impact vaccine effectiveness, are largely ignored in conventional approaches.

Vaccines developed through ‘rational vaccinology’ offer precise dosing for maximum effectiveness
This approach to systematically control antigen and adjuvant locations within modular vaccine architectures was created by Mirkin, who coined the term rational vaccinology to describe it. It is based on the concept that the structural presentation of vaccine components is as important as the components themselves in driving efficacy.
“Vaccines developed through rational vaccinology deliver the precise dose of antigen and adjuvant to every immune cell, so they are all equally primed to attack cancer cells,” said Mirkin, who also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “If your immune cells are soldiers, a traditional vaccine leaves some unarmed; our vaccine arms them all with a powerful weapon with which to kill cancer. Which immune cell ‘soldiers’ do you want to attack your cancer cells?” Mirkin asked rhetorically.
Building an (even) better vaccine
The team developed a cancer vaccine that doubled the number of cancer antigen-specific T cells and increased the activation of these cells by 30% by reconfiguring the architecture of the vaccine to contain multiple targets to help the immune system find tumor cells.
The team investigated differences in how well two antigens were recognized by the immune system depending on their placement — on the core or perimeter — of the SNA structure. For an SNA with optimum placement, they could increase the immune response and how quickly the nanovaccine triggered cytokine (an immune cell protein) production to boost T cells attacking the cancer cells. The scientists also studied how the different placements affected the immune system’s ability to remember the invader, and whether the memory was long-term.
“Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it,” Mirkin said.
The most powerful structure throws two punches to outsmart the wily, mutating tumor
The study data show that attaching two different antigens to an SNA comprising a shell of adjuvant was the most potent approach for a cancer vaccine structure. It led to a 30% increase in antigen-specific T-cell activation and doubled the number of proliferating T cells compared to a structure in which the same two antigens were attached to two separate SNAs.
These engineered SNA nanostructures stalled tumor growth in multiple animal models.
“It is remarkable,” Mirkin said. “When altering the placement of antigens in two vaccines that are nearly identical from a compositional standpoint, the treatment benefit against tumors is dramatically changed. One vaccine is potent and useful, while the other is much less effective.”
Many current cancer vaccines are designed to primarily activate cytotoxic T cells, only one defense against a cancer cell. Because tumor cells are always mutating, they can easily escape this immune cell surveillance, quickly rendering the vaccine ineffective. The odds are higher that the T cell will recognize a mutating cancer cell if it has more ways — multiple antigens — to recognize it.
“You need more than one type of T cell activated, so you can more easily attack a tumor cell,” Teplensky said. “The more types of cells the immune system has to go after tumors, the better. Vaccines consisting of multiple antigens targeting multiple immune cell types are necessary to induce enhanced and long-lasting tumor remission.”
Another advantage of the rational vaccinology approach, especially when used with a nanostructure like an SNA, is that it’s easy to alter the structure of a vaccine to go after a different type of disease. Mirkin said they simply switch out a peptide, a snippet of a cancer protein with a chemical handle that “clips” onto the structure, not unlike adding a new charm to a bracelet.
Path to most effective vaccine for any cancer type
“The collective importance of this work is that it lays the foundation for developing the most effective forms of vaccine for almost any type of cancer,” Teplensky said. “It is about redefining how we develop vaccines across the board, including ones for infectious diseases.”
In a previously published paper, Mirkin, Teplensky and colleagues demonstrated the importance of vaccine structure for COVID-19 by creating vaccines that exhibited protective immunity in 100% of animals against a lethal viral infection.
“Small changes in antigen placement on a vaccine significantly elevate cell-to-cell communication, cross-talk and cell synergy,” Mirkin said. “The developments made in this work provide a path forward to rethinking the design of vaccines for cancer and other diseases as a whole.”
Northwestern Ph.D. candidate Michael Evangelopoulos also is an author of the paper, titled “Multi-Antigen Spherical Nucleic Acid Cancer Vaccines.”
Founded in 2000 as an umbrella organization to coalesce and foster nanotechnology efforts, the IIN represents and unites more than $1 billion in nanotechnology research, educational programs, and supporting infrastructure.
This study is based upon work supported by the Polsky Urologic Cancer Institute of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, Edward Bachrach and the National Cancer Institute of the National Institutes of Health (R01CA208783, R01CA257926, and P50CA221747). Teplensky also received support from Northwestern University’s Cancer Nanotechnology Training Program Award (T32CA186897). Evangelopoulos was partially supported by the Dr. John N. Nicholson Fellowship and the Alexander S. Onassis Public Benefit Foundation.

Proper sleep is critical for the maintenance of good health, and vice versa — a healthy lifestyle has been found to improve sleep quality. To better examine the relationship between physical activity and sleep, a team of researchers conducted a comprehensive study among middle-aged Japanese people. By outlining the factors improving sleep quality, this line of research can hopefully help in preventing sleep-related disorders.
An adequate amount of good-quality sleep is essential for the physical and emotional well-being of humans. For instance, good-quality sleep helps improve the outcomes of various diseases, including cardiovascular and metabolic disorders, mental diseases, and dementia. On the other hand, sleep disorders such as insomnia, narcolepsy, and excessive sleepiness may lead to serious health issues and are quite prevalent the world over. In the USA, 50-70 million adults suffer from sleep disorders, primarily insomnia. Meanwhile, a meta-analysis of 17 studies suggested that in China, insomnia is present in 15% of the population. To better understand such ailments, it is important to study the factors that promote good-quality sleep. Previous studies have indicated that a proper lifestyle, including a healthy diet and regular physical activity, is beneficial for good sleep. However, a systematic comprehensive study is lacking in this area of research.
To this end, a team of researchers from Japan, Canada, and Taiwan — led by Associate Professor Javad Koohsari from the School of Knowledge Science at Japan Advanced Institute of Science and Technology (JAIST), who is also an adjunct researcher at the Faculty of Sport Sciences at Waseda University, — has probed the inter-relationship between sedentary behaviour, physical activity, and sleep quality in a sample of middle-aged Japanese population. The research group, comprising Professor Yukari Nagai, also from JAIST; Professor Akitomo Yasunaga from Bunka Gakuen University; Associate Professor Ai Shibata from University of Tsukuba; Professor Yung Liao from National Taiwan Normal University; Associate Professor Gavin R. McCormack from University of Calgary, and Professor Koichiro Oka and Professor Kaori Ishii from Waseda University, based their study on Japanese adults between 40 and 64 years of age — a crucial time window which often marks the onset of various health issues. Their work has been recently published in Scientific Reports.
The researchers used an isotemporal substitution approach, which estimates the effect of replacing one activity type with another for the same amount of time. Says Dr. Koohsari, “We replaced 60 minutes of sedentary behaviour or light-intensity physical activity with moderate-to-vigorous physical activity in the participants’ schedules.” An accelerometer monitored the participants’ level of physical activity for seven consecutive days. A questionnaire was then used to assess the participants’ quality of sleep and rest.
The replacement of sedentary behaviour with moderate-to-intense exercise indeed improved sleep quality. Interestingly, this association was seen to be gender-based, and was only found in women. This is in agreement with reports that have shed light on gender-based differences in sleep disorders. More studies are, however, required to understand why these gender-based dissimilarities occur.
In summary, this study contributes to the existing pool of studies that provide empirical evidence of the importance of physical activity in promoting good-quality sleep. Hopefully, these studies will serve as a useful platform for further research on the prevention of sleep-related disorders. Surely, we now have enough motivation for regularizing our workout schedules!

A research team led by Professor Xiang David LI from the Department of Chemistry at The University of Hong Kong (HKU) has developed a novel chemical tool to reveal how bacteria adapt to the host environment and control host cells. This tool can be used to investigate bacterial interactions with the host in real-time during an infection, which cannot be easily achieved by other methods. The findings were recently published in Nature Chemical Biology.
Pathogenic bacteria, while only numbering fewer than a hundred, heavily threaten human health all over the world. For example, Mycobacterium tuberculosis infection causes tuberculosis, which leads to more than one million deaths each year. It was the world’s deadliest infectious disease until it was overtaken by COVID-19. Despite effective antibiotic treatments, multiple drug-resistant tuberculosis has become a growing problem worldwide. Therefore, a more comprehensive understanding of how bacteria infect their human host is key to developing new drugs and therapies.
When bacteria meet their host (e.g., human cells), they send out ‘assassins’ (virulence factor proteins) that ‘hijack’ important protein players of the host to sow chaos during an invasion. Therefore, investigating which virulence factors bacteria secrete and which host proteins are targeted is crucial for the understanding of bacterial infections. However, it can be extremely challenging to identify these key players among the ‘crowded streets’ (excessive host cellular matrix).
To tackle this challenge, Professor Li’s group designed a multifunctional unnatural amino acid called photo-ANA that only labels proteins of the engineered bacteria but not the host during infection. With the help of its alkyne handle, photo-ANA can conjugate with fluorescence or biotin via a Nobel prize-winning chemical reaction (‘click’ chemistry), which enables the visualisation and enrichment of the labelled bacterial proteins from the complex host environment. Thus, Photo-ANA serves as an ‘undercover agent’ to gather intelligence and tag all the ‘assassins’ sent by the bacteria. More importantly, photo-ANA also carries a diazirine group that can ‘handcuff’ the bacterial virulence proteins to their host target proteins upon exposure to ultraviolet (UV) light — catching them in the act.
Using photo-ANA, Professor Li’s group comprehensively profiled the adaptation of Salmonella, bacteria that can cause severe diarrhea, to the host environment and revealed the extensive interplay between Salmonella and the host during different infection stages, which identified known interactions and some newly discovered interactions. Moreover, the photo-ANA-based approach can be easily applied to other pathogenic bacteria and even other pathogens such as fungi.
With this new chemical tool, scientists can now investigate the activity of bacteria inside the host in real-time. In the future, this tool may help us decipher the hidden interactions of deadly bacteria with the host and the mechanisms of multidrug-resistant superbugs, which will further our understanding of infectious diseases and inspire new treatments.

Memory loss, behavioural changes, cognitive deficits: Alzheimer’s disease leads to a dramatic loss of autonomy for those affected and has a heavy impact on health costs. Its prevention has become a real social challenge. An international task force, led by the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), is setting out guidelines for innovative services to prevent Alzheimer’s disease. These will soon be an integral part of second generation memory clinics. These guidelines are detailed in an article published in the Lancet Regional Health — Europe.
With 10 million people affected in Europe, Alzheimer’s disease is the most common neurodegenerative disease. It is characterised by progressive disabling memory loss and cognitive deficits caused by an accumulation of toxic proteins in the brain. Its social and economic impact is considerable. On a global scale, it is estimated to be worth around USD 1,500 billion per year* and in Switzerland CHF 11.8 billion per year**.
Large-scale preventive protocol
Improved lifestyles (physical activity, attention to nutrition, cardiovascular prevention) have reduced the risk of developing Alzheimer’s disease or related forms. However, the prevalence of dementia continues to rise with the ageing population. Today, an international task force led by the UNIGE and the HUG, and composed of scientists from twenty-eight institutions, is laying the foundations of a preventive protocol that could be deployed on a large scale.
”We based this protocol on the experience of all the members of the task force. Some of the recommended interventions are ready to be applied or are already applied. Others are still under development,” explains Giovanni Frisoni, Full Professor of Clinical Neuroscience at the UNIGE Faculty of Medicine and Director of the HUG Memory Centre. Professor Frisoni and the co-authors of the article have identified four pillars of this novel concept in the field of dementia and Alzheimer’s: risk assessment; risk communication; risk reduction and cognitive enhancement.
I. Risk assessment
The risk factors for Alzheimer’s disease or related disorders and their weight have been grouped together in an evaluation grid. These include factors associated with genes, such as APOE4, or those linked to lifestyle or conditions, such as hypertension, diabetes, alcohol consumption, social isolation, obesity, hearing loss, depression or head trauma.

II. Risk communication
This second pillar — which is crucial in the relationship that is established with the patient — makes it possible to communicate the risk index in the most accurate and comprehensible way. Indeed, understanding the risk of developing a disease is more complex than understanding being actually affected by a disease. A series of recommendations based on the patient’s personality and background make it possible to choose the best tools for presenting the situation to the patient in a comprehensible manner.
III. Risk reduction
Drug and non-drug interventions are proposed for risk reduction. These range from lifestyle improvements to cognitive training and the administration of anti-amyloid drugs, if these become available on the market. Interventions on the gut microbiota may also be considered in the future.
IV. Cognitive reinforcement
Different types of memory (subjective, objective, meta) can be reinforced or stimulated through paper-based exercises or computer games. Transcranial electrical or magnetic stimulation will also be an important tool to activate synapses in key brain regions and thus improve memory.

These four pillars detailed in the Lancet Regional Health — Europe article will enable second generation memory clinics to reach out to the segment of the population whose memory is still functioning well and who wish to preserve or improve it. This population does not find answers in the current clinics.
*The worlwide costs of dementia 2015 and comparisons with 2010, Alzheimer’s and Dementia, Elsevier, 2017
**Coûts des démences en Suisse, Alzheimer Suisse, 2019

A new study led by scientists at The Neuro (Montreal Neurological Institute-Hospital) of McGill University finds a correlation between neurodegeneration in obese people and Alzheimer’s disease (AD) patients, suggesting that losing excess weight could slow cognitive decline in aging and lower risk for AD.
Previous research has shown that obesity is linked with Alzheimer’s disease (AD)-related changes, such as cerebrovascular damage and amyloid-β accumulation. However, to date no research has made a direct comparison between brain atrophy patterns in AD and obesity.
Using a sample of over 1,300 individuals, the researchers compared patterns of grey matter atrophy in obesity and AD. They compared the AD patients with healthy controls, and obese with non-obese individuals, creating maps of grey matter atrophy for each group.
The scientists found that obesity and AD affected grey matter cortical thinning in similar ways. For example, thinning in the right temporo-parietal cortex and left prefrontal cortex were similar in both groups. Cortical thinning may be a sign of neurodegeneration. This suggests that obesity may cause the same type of neurodegeneration as found in people with AD.
Obesity is increasingly recognized as a multisystem disease affecting respiratory, gastrointestinal, and cardiovascular systems, among others. Published in the Journal of Alzheimer’s Disease on Jan. 31, 2022, this study helps reveal a neurological impact as well, showing obesity may play a role in the development of Alzheimer’s and dementia.
“Our study strengthens previous literature pointing to obesity as a significant factor in AD by showing that cortical thinning might be one of the potential risk mechanisms,” says Filip Morys, a PhD researcher at The Neuro and the study’s first author. “Our results highlight the importance of decreasing weight in obese and overweight individuals in mid-life, to decrease the subsequent risk of neurodegeneration and dementia.”
This study was funded with a Foundation Scheme award to AD from the Canadian Institutes of Health Research, computing resources from Calcul Quebec and Compute Canada, and by a postdoctoral fellowship from Fonds de Recherche du Québec — Santé.

Several progressive neurodegenerative disorders, including Alzheimer’s disease, are defined by having tau proteins in the brain. Researchers are seeking to identify the mechanisms behind these tau proteins to develop treatments, however, their efforts to detect biomarkers in blood has been hampered by the protective blood-brain barrier.
At Washington University in St. Louis, new research from the lab of Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology in the School of Medicine, and collaborators found that using focused-ultrasound-mediated liquid biopsy in a mouse model released more tau proteins and another biomarker into the blood than without the intervention. This noninvasive method could facilitate diagnosis of neurodegenerative disorders, the researchers said.
The method, known as sonobiopsy, uses focused ultrasound to target a precise location in the brain. Once located, the researchers inject microbubbles into the blood that travel to the ultrasound-targeted tissue and pulsate, which safely opens the blood-brain barrier. The temporary openings allow biomarkers, such as tau proteins and neurofilament light chain protein (NfL), both indicative of neurodegenerative disorders, to pass through the blood-brain barrier and release into the blood.
Chen teamed with co-senior author Arash Nazeri, MD, an assistant professor of radiology at the School of Medicine’s Mallinckrodt Institute of Radiology (MIR). They collaborated with Tammie LS Benzinger, MD, PhD, a professor of radiology at MIR and a professor of neurological surgery and of biology and biological sciences; Eric Leuthardt, MD, a professor of neurosurgery at the School of Medicine and of biomedical engineering at McKelvey Engineering; as well as first author Christopher Pham Pacia, who earned a doctorate in biomedical engineering from Washington University earlier this year; Jinyun Yuan, a research scientist in Chen’s lab; and Yimei Yue, a research technician in Chen’s lab.
Results of the work, the first to open the door for noninvasive and targeted diagnosis and monitoring of neurodegenerative disorders with focused-ultrasound-mediated liquid biopsy, are published in Radiology Jan. 31.
Chen, Leuthardt, Pacia and other collaborators have been working on the sonobiopsy technique for several years, first with biomarkers for human brain cancer in preclinical models. Other liquid biopsy methods used to detect biomarkers for neurodegenerative disorders have multiple challenges, including lacking anatomical information on the location of the protein release, rapid clearance from the fluids and a filtering process by the blood-brain barrier. Chen said sonobiopsy is an emerging technique with the potential to address these and other challenges.
In the new research, the team first took blood samples from young mice with abnormal tau proteins in the brain, or tauopathy, receiving either sonobiopsy or sham treatment. They found that sonobiopsy resulted in a 1.7-fold-increase in the normalized phosphorylated pTau-181 tau protein levels and a 1.4-fold increase in normalized pTau-231 compared with the control mouse group that had not had sonobiopsy. In a follow-up study, they performed targeted sonobiopsy by targeting either the hippocampus or cerebral cortex in the early neurodegenerative stages of the tauopathy model and took blood samples before and after sonobiopsy. The targeted sonobiopsy resulted in a 2.3-fold increase in NfL protein, a secondary biomarker for neurodegenerative diseases, in the treated mice compared with the control group.
“In our proof-of-concept study, we sought to determine whether sonobiopsy is able to release phosphorylated tau species and NfL into the bloodstream by opening the blood-brain barrier,” Chen said. “This demonstration showed that sonobiopsy significantly enhanced the release of pTau proteins and a secondary marker of neurodegeneration into the bloodstream for noninvasive diagnosis for neurodegenerative diseases.”
Nazeri said tauopathies such as Alzheimer’s disease are similar to brain tumors.
“While brain tumor behavior and treatment response are dictated by the specific mutations they harbor, the tau protein shows great heterogeneity in the pattern of phosphorylation as well as other post-translational modifications,” Nazeri said. “Current PET imaging and recently developed plasma biomarkers are sensitive to detect tauopathies even in early stages. Sonobiopsy could potentially play a role to further characterize the specific strains of tau protein present in the brain for personalized treatment of people with Alzheimer’s disease and other tauopathies.”
Going forward, the team will examine the qualitative effects of sonobiopsy on plasma biomarkers and characterize the effects of focused ultrasound parameters and determine an optimal blood collection time, as well as determining how sonobiopsy can be applied to release larger brain-derived protein biomarkers.

A new study shows that sleep medications increase the risk of dementia in whites. But the type and quantity of the medication may be factors in explaining the higher risk.
It follows previous work that shows Blacks have a higher likelihood than whites of developing Alzheimer’s, the most common type of dementia, and that they have different risk factors and disease manifestation.
The final corrected draft of the study publishes in the Journal of Alzheimer’s Disease on Jan. 31, 2023.
In the study, approximately 3,000 older adults without dementia, who lived outside of nursing homes, were enrolled in the Health, Aging and Body Composition study and followed over an average duration of nine years. Their average age was 74; 42% were Black and 58% were white.
During the study, 20% developed dementia. White participants who “often” or “almost always” took sleep medications had a 79% higher chance of developing dementia compared to those who “never” or “rarely” used them. Among Black participants — whose consumption of sleep aids was markedly lower — frequent users had a similar likelihood of developing dementia than those who abstained or rarely used the medications.
Higher-Income Blacks May Be Less Likely to Get Dementia
“Differences may be attributed to socio-economic status” said first author Yue Leng, PhD, of the UCSF Department of Psychiatry and Behavioral Sciences and Weill Institute for Neurosciences. “Black participants who have access to sleep medications might be a select group with high socio-economic status and, thus, greater cognitive reserve, making them less susceptible to dementia.
“It’s also possible that some sleep medications were associated with a higher risk of dementia than others.”
The researchers found that whites, at 7.7%, were three times as likely as Blacks, at 2.7%, to take sleep medications often, five to 15 times a month, or almost always, 16 times a month to daily. Whites were almost twice as likely to use benzodiazepines, like Halcion, Dalmane and Restoril, prescribed for chronic insomnia.
Whites were also 10 times as likely to take trazodone, an antidepressant known by the trade names of Desyrel and Oleptro, that may also be prescribed as a sleep aid. And they were more than seven times as likely to take “Z-drugs,” such as Ambien, a so-called sedative-hypnotic.
While future study may offer clarity on the cognitive risks or rewards of sleep medications and the role that race may play, patients with poor sleep should hesitate before considering medications, according to Leng.
“The first step is to determine what kind of sleep issues patients are dealing with. A sleep test may be required if sleep apnea is a possibility,” she said. “If insomnia is diagnosed, cognitive behavioral therapy for insomnia (CBT-i) is the first-line treatment. If medication is to be used, melatonin might be a safer option, but we need more evidence to understand its long-term impact on health.”