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Nearly three years into the pandemic, many of us now carry antibodies against the virus — due to an infection or two, a few doses of mRNA vaccine, or a round of monoclonal-antibody treatment. But not all immune responses are created equal, and how we first developed our antibodies may influence the character of our body’s response to SARS-CoV-2.
Now, a new study describes the unique immune response elicited in individuals who received monoclonal antibodies before taking two doses of an mRNA vaccine. The research, published in Nature, explores a phenomenon known as antibody feedback inhibition, known to alter immune responses to some pathogens while beneficially diversifying the body’s antibody repertoire against several others. The findings suggest that feedback inhibition increases the coverage provided by COVID vaccines in people who previously received monoclonal antibodies.
“Depending on the virus, feedback inhibition can either enhance immunity or inhibit it,” says Michel C. Nussenzweig, who co-led the study with colleagues Theodora Hatziioannou, Paul Bieniasz, and Marina Caskey. “Our results suggest that pre-existing SARS-CoV-2 antibodies can diversify the antibody response, which may increase the breadth of mRNA vaccines.”
Of guinea pigs and antibodies
Antibody feedback inhibition was first discovered at the turn of the century by pioneering epidemiologist Theobald Smith, who demonstrated that excess antibodies could inhibit the immune response to diphtheria in guinea pigs. It seemed like a curious twist — why would the same molecule that supposedly protects the animal from disease occasionally shut the immune system down?
We now know that viruses have multiple epitopes — stand-out bits of antigen that antibodies use to identify the virus and latch on to it. Once the body has produced strong antibodies for one epitope, the immune system moves on and diversifies, instead making antibodies that attach to other parts of the virus. Ideally, this increases the breadth of the immune response — if a virus mutates so that one epitope can no longer be recognized, for example, it might still be vulnerable to antibodies targeting other epitopes.

As climate change continues, human cases of rat lungworm disease are anticipated to become more widespread globally, especially in places where the parasite that causes the disease is not yet present. A review paper, led by University of Hawaiʻi at Mānoa researchers, was published to educate medical professionals in the U.S. and around the world as they encounter an increasing number of patients with the disease.
“We published this paper as a means to broaden knowledge and understanding of rat lungworm disease, especially among the medical community but also to help spread the word to the general public,” said Robert Cowie, lead author of the study and research professor at the Pacific Biosciences Research Center in the UH Mānoa School of Ocean and Earth Science and Technology.
Increased awareness among the medical community will reduce the likelihood of sick people being misdiagnosed in primary care clinics and emergency rooms or simply being given pain medicine and anti-anxiety medication, or of infected individuals waiting weeks to months before receiving an accurate diagnosis.
Rats and slugs or snails are required hosts during various stages of the rat lungworm’s life cycle. Humans become infected after inadvertently or intentionally eating a raw or undercooked, infected slug/snail or other so-called “carrier” hosts in which the parasite cannot develop, such as freshwater prawns, frogs, toads, centipedes, or land crabs. When people are infected, the rat lungworm’s migration into the brain and spinal cord combined with a powerful inflammatory reaction often leads to swelling around the brain and spinal cord (meningitis) and can, in rare instances, lead to paralysis and death or, in other cases, chronic, disabling neurological symptoms.
The study, published in the American Journal of Tropical Medicine and Hygiene, summarizes and provides references to literature dealing with diagnosis and treatment including guidance shared in a 2020 publication led by Vernon Ansdell, associate professor at the UH Mānoa John A. Burns School of Medicine and co-author of the new study.
Early diagnosis, treatment are critical
Cowie, Ansdell and their co-authors highlight the challenges posed by the wide array of symptoms rat lungworm disease can induce — headache, fever, nausea, rash, anxiety, migratory pains, tingling of the skin which may become super-sensitive, weakness and more.

One of the major challenges in microbiome science has been distinguishing what is a potential environmental contaminant from a true, bona fide microbiome signal in low biomass studies — studies that contain little microbial DNA like breastmilk, placenta or amniotic fluid. For instance, it can be challenging to differentiate between the DNA of a microbe in a sample from remnant contaminant DNA from a sampling kit or extraction kit or the environment.
While researchers normally include negative controls from the equipment or environment and use algorithmic tools to identify microorganisms present in the environment, not all datasets come with negative controls. Researchers at Baylor College of Medicine and Rice University developed a new contamination detection tool to establish reproducibility in the identification and analysis of the microbes. Their findings were recently published in Nature Communications.
“We teamed up with our collaborators at Rice University to develop and test a computational tool we called Squeegee,” said Dr. Kjersti Aagaard, professor of obstetrics and gynecology at Baylor and Texas Children’s Hospital. “The premise of Squeegee is that we can use a computer analysis pipeline to help us detect ‘breadcrumbs’ of contaminants that would be anticipated to be common between the microbiome found in all human (or other mammalian) hosts and the sampling or lab environment.”
The Aagaard Lab at Baylor has conducted IRB-approved and NIH-funded research over the last decade leading to a number of rich datasets from a large number of participants that are particularly low biomass and have many negative controls. They teamed up with researchers at Rice’s Treangen Lab to test Squeegee, an algorithm used on life datasets from human studies that had contamination controls from different environments and DNA extraction kits. They looked at the false positive rate, the recall and how accurately Squeegee could predict and flag these environmental contamination sets with the absence of the negative control.
“We were able to show that Squeegee was capable of having a high-weighted recall and a very low false-positive rate in these ground truth datasets,” said Dr. Michael Jochum, postdoctoral research associate in the Department of Obstetrics and Gynecology Baylor.
According to Jochum, Squeegee improves the overall reliability of metagenomic sequencing analysis results in low biomass studies. The new contamination identification tool is capable of identifying batch effects, flagging them as potential contaminants. Given the focus and expertise of the Aagaard lab in studying these sparse microbial environments, this is a tool that they have added to their toolbox for ongoing and future studies.
“Squeegee is a first-of-its-kind tool for the microbiome science community, and it is freely available for use,” Aagaard said.
The source code for Squeegee is publicly available at https://gitlab.com/treangenlab/squeegee
Other contributors to this work include Dr. Yunxi Liu, Dr. R.A. Leo Elworth and Dr. Todd Treangen.
This work was funded by National Institutes of Health and the National Science Foundation.
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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

Spurred by the infant formula crisis, a panel found that the agency shied away from tough decisions, sometimes fearing confrontations with industry over enforcement of critical public health issues.The Food and Drug Administration’s food division has no clear leadership, avoids bold policy or enforcement actions, and fosters a culture that doesn’t adequately protect public health, according to a report issued on Tuesday by an agency-related group.Experts with the group, the Reagan-Udall Foundation, which was asked to examine the food division after widespread criticism stemming from the infant formula crisis, concluded in the report that the division’s management structure and mission should be overhauled.Dr. Robert Califf, the agency commissioner, released a statement Tuesday saying he would form a group to advise him on the findings and on how to put the recommendations in place. The infant formula crisis was the first major challenge that Dr. Califf confronted this year as commissioner, although the agency has also faced criticism over the regulation of vaping and tobacco products, which prompted a similar review of its tobacco division.“I expect this leadership group to be bold and focused on the transformative opportunities ahead for the F.D.A.’s food program,” Dr. Califf said. “I will be fully engaged to ensure that the program comes out of this transition with the resources, tools and visibility it warrants given how critical its work is to every American.”Congressional lawmakers and others have long called for strengthening the authority and influence of the agency’s food division, given the effects of foods like added sugar and salt on deadly chronic diseases and the toll of food-borne illnesses that account for an estimated 128,000 U.S. hospitalizations and 3,000 deaths each year.The report followed years of complaints that the food unit was toothless, a criticism that was amplified by what critics viewed as the agency’s plodding and disorganized response to reports of infant illness and death and unsanitary conditions at the Abbott Nutrition infant formula plant in Michigan. The agency’s shutdown of the factory in February aggravated an infant formula shortage that left parents scrambling to feed their babies for months earlier this year.A New York Times review found that the F.D.A. had fielded a complaint in September 2021 about a Minnesota infant hospitalized with the deadly Cronobactor sakazakii bacteria, reportedly after consuming formula from the plant. Yet even though agency inspectors inspected the plant in Sturgis, Mich., at the time, it was not until February that the authorities swabbed the plant and discovered the bacteria near production areas. Abbott has said that genetic sequencing did not connect bacteria found in the plant to the deaths of infants infected with Cronobactor.Representative Rosa DeLauro, Democrat of Connecticut and chairwoman of the House Appropriations Committee, which oversees the agency, said in a statement that she was “pleasantly surprised by the formal acknowledgment of the issues that plague the F.D.A. foods program.”“I look forward to working with the F.D.A. on how they intend to implement the positive reforms in this report,” Ms. DeLauro said.Food safety advocates who have been harsh critics of the agency said the report appeared detailed and strong enough to pave the way for needed change.“It’s very significant and encouraging from that standpoint, because for them to outline the findings that they did is important, because it’s a critical acknowledgment that things definitely need to change,” Brian Ronholm, director of food policy for Consumer Reports, said. “Now it comes down to: How does F.D.A. process this report and the information contained in it, and how does that translate to meaningful reform?”Some critics, however, pointed to the relationship the report’s authors have with the agency. The Reagan-Udall Foundation is funded by the F.D.A. and major corporations like Pfizer, AbbVie and Nestle USA, which makes infant formula. The foundation sought the views of food safety and nutrition experts and collated the comments of agency staff members, but has since removed the feedback from its website.The staff comments, reviewed by The Times, showed some discontent with how the division was run. Some employees repeatedly complained that division managers stopped short of enforcing food-safety laws out of fear of complaints or lawsuits. Others said that input from industry consultants and special advisers from industry added little value. And some others chafed about a lack of clear priorities, or personality politics and favoritism that trumped a focus on protecting the nation’s food supply.Four former F.D.A. food center directors submitted a statement calling for the division to be better protected from budget cuts and for giving its officials more control over food facility inspections.The report underscores that concern about lack of leadership, noting that three food division officials have competing levels of authority. The report recommends a structural change, laying out several options that would make leadership more centralized. It also recommended more funding to enhance the division’s operations, although congressional approval for budgetary increases might prove difficult now that inflation and the economy may force cutbacks.

Researchers with the Rutgers Environmental and Occupational Health Sciences Institute have simulated how climate change will affect the distribution of two leading allergens — oak and ragweed pollens — across the contiguous United States. The results, published in the journal Frontiers in Allergy, may make your eyes water.
Using computer models, the team, led by Panos Georgopoulos, a professor of Environmental and Occupational Health and Justice at the Rutgers School of Public Health, found that by 2050 climate change significantly will increase airborne pollen loads, with some of the largest surges occurring in areas where pollen is historically uncommon.
“Pollen is an excellent sentinel for the impacts of climate change because shifts in variables like carbon dioxide and temperature affect the way plants behave,” said Georgopoulos, who also is director of the Computational Chemodynamics Laboratory at Rutgers and faculty at Robert Wood Johnson Medical School. “At the same time, the production of pollen and pollen’s influence on allergic disease has been increasing due to climate change, and this is one of few studies to forecast this trend into the future.”
Previous efforts to connect pollen indices with climate change have been limited by a scarcity of data. For instance, there are about 80 pollen sampling stations in the U.S., operated by a variety of private and public agencies using different sampling methods.
To overcome this challenge, the researchers adapted the Community Multiscale Air Quality modeling system, an open-source tool managed by the U.S. Environmental Protection Agency (EPA) to simulate distributions of allergenic oak and ragweed pollen for historical (2004) and future (2047) conditions.
Results showed that even under moderate warming conditions, pollen season will start earlier and last longer throughout the U.S., with increasing average pollen concentrations in most parts of the nation. Mean concentrations of oak pollen could climb by more than 40 percent in the Northeast and Southwest and mean concentrations of ragweed could jump by more than 20 percent in these areas.
Regional pollen shifts were observed, too. In parts of Nevada and northern Texas, oak pollen levels could double by mid-century, while Massachusetts and Virginia could see an 80 percent increase in ragweed pollen by 2050.
The pollen research was part of an ongoing project by the Rutgers Ozone Research Center, which is funded by the EPA and New Jersey to study how climate change will influence air quality in the state. The bulk of that work examines the state’s struggles with ground level ozone, a byproduct of fossil fuel combustion that can damage the lungs.
“New Jersey’s air quality is going to be adversely impacted by climate change, both in terms of anthropogenic pollution and increased levels of pollen,” Georgopoulos said. “For people with asthma, exposure to pollen and irritants like ozone increases the odds of respiratory illness. To protect the most vulnerable, we need to understand how these irritants will behave in a warming world.”
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Materials provided by Rutgers University. Original written by Greg Bruno. Note: Content may be edited for style and length.

At the heart of every CRISPR reaction, whether naturally occurring in bacteria or harnessed by CRIPSR-Cas gene editing technology, is a strong molecular bond of a Cas protein via a guide RNA to its target site on DNA. It’s like a nanoscale ski binding.
“There’s a balance between stably bound and coming off at the right time,” said Michelle Wang, the James Gilbert White Distinguished Professor of the Physical Sciences and Howard Hughes Medical Institute Investigator in the College of Arts and Sciences. “What we really want is the ability to modulate the affinity. That gives us the possibility of fine-tuning the gene editing potential.”
A Cas protein binding can’t be too transient, according to Porter Hall, a biophysics doctoral candidate in the Wang Lab and the lead author of the publication. If it can’t stably bind the target region of the DNA, precise gene editing may not be efficient, potentially leading to off-target effects. “But if the protein stays there forever, then the gene editing process cannot be completed,” Hall said.
Examining the precise, molecular-level mechanisms involved in Cas binding to DNA, Wang and colleagues give the first mechanistic explanation of how a motor protein (RNA polymerase) removes a bound dCas, a version of Cas engineered to recognize a DNA sequence without performing a cut.
This insight reveals how to tune Cas removal, contributing to future CRISPR applications.
“Polarity of the CRISPR Roadblock to Transcription” published Dec. 5 in Nature Structural & Molecular Biology. Other contributors are lab members James Inman, Robert Fulbright and Tung Le, along with collaborators Guillaume Lambert, assistant professor in applied and engineering physics, Cornell Engineering, and Joshua Brewer and Seth Darst from the Rockefeller University.

Preventing metastasis — the development of cancer cells beyond their original location — remains one of the major goals of current cancer research. Most malignant tumor cells metastasize by exploiting abnormal leakage from blood vessels. New work looks to further explore the role of how the alignment of endothelial cells, which line blood vessels, plays a role in the spread of cancer.
In APL Bioengineering, by AIP Publishing, researchers from the University of Michigan-Dearborn, Rensselaer Polytechnic Institute, and the University at Albany — SUNY developed a model that examines the local communication between endothelial cells and tumors cells and its effects on endothelial cell orientation. The approach involves the use of co-cultured human umbilical vein endothelial cells (hUVECs) and breast epithelial tumor cell lines to simulate the tumor-endothelial interaction.
“The blood vessels in tumor tissues are much leakier than those in normal tissues,” said author Jie Fan. “We are curious whether the tumor cells can induce the weakening in the clockwise orientation of endothelial cells and cause them to disorganize in the vessel.”
The work expands on recent findings that showed that endothelial cells have chirality, a type of mirrored-image orientation similar to right and left hands, and they tend to skew in a clockwise direction.
“We believe the strong clockwise chirality of endothelial cells is important to maintain blood vessel integrity, but unfortunately, it could be damaged/weakened by tumor cells, which may increase the risk of metastasis,” Fan said. “Preserving the normal chirality could inhibit tumor transmigration by reinforcing the chirality and the integrity of the endothelial barrier of blood vessels.”
To address the question, the group co-cultured hUVECs with a series of tumor cell lines with varying degrees of malignancy. They then compared how hUVECs responded when the tumor cells were directly touching them versus not. To exert such a degree of control, they employed a contact printing technique to create either donut- or figure eight-shaped micropatterns to hold the cells.
The group found the clockwise chirality of the hUVECs was less affected by local hormone signaling and more so by direct physical contact with tumor cells. Specific proteins on the tumor cell binding to others on endothelial cells appeared to play a role in changing the clockwise chirality of hUVECs.
The group was surprised by the movement of the cell types. In most models for metastasis, it is thought that tumor cells march toward blood vessels before breaking through into the bloodstream.
“We had expected the tumor cell would invade the endothelial cell,” Fan said. “However, we found the endothelial cells were moving towards the tumor cell on the micropattern.”
Fan said regulating this interaction holds promise for better controlling cancer metastasis and he hopes to work further on developing therapeutics toward this end.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

A small molecule inhibitor that attacks the difficult to target, cancer-causing gene mutation KRAS, found in nearly 30 percent of all human tumors, successfully shrunk tumors or stopped cancer growth in preclinical models of pancreatic cancer, researchers from Penn Medicine’s Abramson Cancer Center showed, suggesting the drug is a strong candidate for clinical trials. The study was published today in Cancer Discovery, a journal of the American Association for Cancer Research.
“The results of this study are in stark contrast to anything we’ve seen before in pancreatic cancer,” said co-corresponding senior author Ben Stanger, MD, PhD, the Hanna Wise Professor in Cancer Research in the Perelman School of Medicine at the University of Pennsylvania and director of the Penn Pancreatic Cancer Research Center. “Even in preclinical research models for this cancer type, most drugs tested within the last decade — including novel immunotherapies — have had limited impact.”
Patients with pancreatic cancer have an overall poor prognosis with a five-year survival rate of 11 percent and limited treatment options. Nearly 90 percent of pancreatic cancers are driven by a mutation in the KRAS gene, the most common oncogene across cancer types. The first targeted therapy for KRAS was approved last year for non-small cell lung cancer with KRAS G12C mutations, but only 2 percent of pancreatic cancers express that type of mutation. Around 36 percent of pancreatic cancers with a KRAS mutation are KRAS G12D-mutant.
The small molecule inhibitor used in this study, MRTX1133 (developed by Mirati Therapeutics) specifically targets KRAS G12D, as the company first reported last month in Nature Medicine. The Penn study now shows the KRAS-inhibitor not only directly targets cancer cells but also unexpectedly cooperates with the immune system to produce a durable response to treatment, which is important because cancer eventually finds a way to evade most targeted therapies.
“We know from KRAS G12Cstudies and other targeted therapy studies that resistance is going to happen,” Stanger said. “Even before we get to clinical trials, we’re thinking about how to combine drugs so that the tumors won’t come back. Our findings provide evidence to suggest immunotherapy as a partner with KRAS G12D inhibitors.”
The researchers were able to assess the impact of MRTX1133 on the immune system because the type of model used in the study allows the tumor to spontaneously evolve after implantation in otherwise healthy mice, making it possible to discern the drug’s impact on the surrounding tumor microenvironment (TME). The immunocompetent KPC model was developed by Penn Medicine nearly 20 years ago and is the gold standard used worldwide to assess potential therapies for pancreatic ductal adenocarcinoma (PDAC). PDAC is known for having a particularly dense TME, which contributes to resistance to therapy.
The research team found that the drug prompted an increase of T cells in the TME, which improved the depth and duration of response to MRTX1133. All complete remissions observed in the study were accompanied by T cell mediated anti-tumor immunity. In mice without T cells, the effect of MRTX1133 was brief and tumors grow back much more quickly. These results suggest that MRTX1133 could be combined with immunotherapy to improve long-term response to therapy and keep the cancer from returning.
“After many years of work to find much-needed new approaches for patients with pancreatic cancer, it’s exciting to have a new class of drugs on the horizon,” said co-corresponding author Robert Vonderheide, MD, DPhil, director of the Abramson Cancer Center and the John H. Glick Abramson Cancer Center Professor in the Perelman School of Medicine, whose lab members worked with those in Stanger’s lab in a focused cooperative team on this study. “We’re optimistic that KRAS G12D inhibitors will make their way into clinical trials soon. KRAS is surrendering, and now we know the immune system can see it.”
The study was supported by the National Institutes of Health (R01-CA229803, R01-CA252225, T32-CA009140 and P30-CA016520), the Cancer Research Institute (CRI4097), the Parker Institute for Cancer
Immunotherapy, the Penn Pancreatic Cancer Research Center and The Abramson Family Cancer Research Institute.

A new antimalarial drug is being introduced at a dose that is too low to be effective for all patients who need it, according to a report published today in eLife.
The study suggests that the current 300 mg adult dose of tafenoquine reduces recurrent vivax malaria infection by 70%, whereas increasing it to 450 mg would reduce recurrence by 85%. This means that for every 11 people treated with the higher dose, an additional person would be cured.
Tafenoquine is the first newly approved anti-relapse drug for 70 years, and its main advantage is that it can be taken as a single dose, unlike primaquine (the current treatment) which needs to be taken daily for 7-14 days.
“The same single dose of tafenoquine is recommended for all adults and this has important practical advantages. However, because of variation in body weight, that dose results in substantial variation in drug exposure,” explains lead author James Watson, a researcher at the Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. “The tafenoquine studies suggested that this single 300 mg dose was inferior to primaquine doses which are lower than those recommended by the WHO in Southeast Asia. Overall, it seems that the currently recommended adult dose of tafenoquine is not as good as optimal primaquine treatment in preventing vivax malaria relapses in all endemic regions.”
To understand more about tafenoquine’s mechanism of action and optimal dosing, the team conducted a meta-analysis in which they pooled data from individual malaria patients who took part in the three clinical trials that led to the drug’s approval, and healthy volunteers involved in an earlier pharmacokinetics study. They then used statistical models to characterise the relationship between the weight-adjusted dose of tafenoquine or primaquine treatment and the likelihood of a recurrent malaria infection.
They found that each additional mg/kg of tafenoquine substantially reduced the chance of having a recurrent vivax malaria infection within four months. For example, increasing the dose from 3mg/kg to 4mg/kg reduces the proportion of patients with a recurrent infection from ~30% to 20%. This association between tafenoquine dose and the proportion relapsing was seen in patients from Asia, Africa and the Americas.
They then used patients’ weight data from the three efficacy trials to calculate the likely average efficacy of tafenoquine with either a 300 mg or 450 mg dose. A fixed tafenoquine dose of 300 mg would result in around 15% of the patients having a recurrence, whereas a dose of 450mg would reduce this proportion to 6%. Given that approximately half the patients given no anti-relapse treatment had a recurrence, this suggests that the lower 300 mg dose prevents 70% of recurrences whereas the 450 mg dose prevents 85% of recurrences.
To study the mechanism of action of tafenoquine, the team combined pharmacokinetics data from the healthy volunteers in the initial study with patients from the efficacy trials — nearly 4,500 drug measurements from 718 individuals. They also measured levels of methaemoglobin, a measure of oxidative activity in the body. These two analyses revealed the drug’s metabolism, reflected by its rate of elimination from the body, rather than exposure to the parent compound, determined its activity in preventing vivax malaria recurrences, and it suggests that the conversion of tafenoquine into oxidative metabolites was responsible for its antimalarial activity, just as for primaquine.
“Our analysis provides strong evidence that the currently recommended adult dose of tafenoquine is insufficient for radical cure in all adults,” concludes senior author Nicholas White, Professor of Tropical Medicine at the Faculty of Tropical Medicine, Mahidol University, Thailand and the Centre for Tropical Medicine and Global Health, University of Oxford. “In endemic areas, relapse of Plasmodium vivax malaria causes substantial morbidity and contributes to mortality, particularly in young children. Tafenoquine can prevent malaria relapses in one treatment dose and is therefore, potentially, a major advance in antimalarial therapeutics. Getting the dose right is critical. The efficacy, tolerability and safety of increased doses should now be evaluated in prospective studies.”
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Materials provided by eLife. Note: Content may be edited for style and length.

Regenstrief Institute Research Scientist April Savoy, PhD, a human factors engineer and health services researcher, is developing and testing user-friendly health information tools and technology designed to enhance accessibility and value to older adults with both diabetes and Alzheimer’s disease, and their caregivers. Without numerous finger sticks, these tools and technology will be designed to provide patients, caregivers, and clinicians with glucose metrics needed to diagnose hypoglycemia and identify treatment options.
Older adults with Alzheimer’s and Type 1 or Type 2 diabetes have a high risk of low blood sugar, known as hypoglycemia, which is often undetected. Hypoglycemia can cause dizziness, confusion, mood changes, hospitalization, and even death. Diagnosis and treatment of hypoglycemia can prevent complications.
“Alzheimer’s disease is a progressive disease, and hypoglycemic events can accelerate cognitive decline. That’s why we are focusing on detection of low blood sugar in these older adults with both Alzheimer’s and diabetes,” said Dr. Savoy, assistant professor in the Purdue School of Engineering and Technology at IUPUI.
Dementia hinders the ability of patients and caregivers to manage blood sugar levels, potentially resulting in hypoglycemic events and further cognitive loss. Repeated finger sticks to test blood sugar levels, following a prescribed diet and exercising can be difficult for patients with Alzheimer’s. Use of traditional blood sugar monitors may be problematic for individuals with Alzheimer’s as well as caregivers.
The study, “Enhancing shared decision-making to prompt and guide individualized care for people with Alzheimer’s Disease and diabetes,” will enroll 75 pairs of older adults with both Alzheimer’s and diabetes, and their family caregivers. Twenty clinicians who see patients with both conditions will also participate.
Other studies have investigated how poor management of diabetes increases risk of dementia. But this new research, implementing a human factors engineering approach, targets older adults who have already been diagnosed with both Alzheimer’s and diabetes. Dr. Savoy and colleagues will investigate unique population dynamics, including how much data about glucose levels are needed, how to acquire them, and what works to enable shared decision-making for all involved — patients, caregivers, and clinicians.
“We hope to increase awareness and empower patients and caregivers to make individualized, patient-focused decisions about effective treatment options. Our goal is to prevent hypoglycemia for the growing population of older adults with Alzheimer’s disease and diabetes,” said Dr. Savoy.
Collaborating with Dr. Savoy on this work, which is supported by a new five-year grant from the National Institutes of Health’s National Institute on Aging, are Regenstrief Institute investigators and Indiana University School of Medicine faculty members Michael Weiner, M.D., MPH, who has conducted research on hypoglycemia and dementia, and Greg Sachs, M.D., a geriatrician focused on the aging brain; Regenstrief Institute and Indiana University School of Public Health-Bloomington faculty member Richard Holden, PhD, a human factors engineer who is developing technology for individuals with Alzheimer’s along with their caregivers; and Indiana University School of Medicine faculty member Mary DeGroot, PhD, who studies and treats patients with diabetes.
Dr. Savoy and colleagues recently authored a commentary in the peer-reviewed Journal of Diabetes Science and Technology, on the importance of applying the human-centered design process to continuous glucose monitoring and investigating design solutions and interventions to integrate continuous glucose monitoring into the healthcare of patients with dementia and diabetes. With the use of human-centered design, the authors indicate that they will be able to identify and inform continuous glucose monitoring designs for people with dementia and diabetes, broadening access to continuous glucose monitoring with what they believe is the attainable goal of increasing detection and treatment of the silent threat posed by low blood sugar.
Authors of “Improving Care for People Living with Dementia and Diabetes: Applying the Human-Centered Design Process to Continuous Glucose Monitoring,” in addition to Dr. Savoy and the collaborators on the new grant (noted above), are Daniel O. Clark, PhD, of Regenstrief Institute and Indiana University School of Medicine, and David Klonoff, M.D., University of California, San Francisco.
This research was supported by the National Institute on Aging of the National Institutes of Health under award number K01AG076971-01.